Bacterial AhpC peroxide reduction and regeneration systems

Bacterial AhpC peroxiredoxins reduce hydroperoxides and are recycled by distinct electron-donor systems. Sampled implementations couple AhpC to AhpF in E. coli, Salmonella and Bacillus, to a thioredoxin/reductase pair in H. pylori and M. tuberculosis, or to the mycobacterial Lpd–lipoyl-DlaT–AhpD relay. Pairing, donor preference, substrate range and oligomeric state are bounded by their native or reconstituted experimental contexts.

MODULE:bacterial_alkyl_hydroperoxide_reductaseCOMPLETECONCRETEMolecular Functionmodules/bacterial_alkyl_hydroperoxide_reductase.yaml
peroxiredoxin activityGO:0051920
url:https://scb.wfu.edu/Poole-files/ABB-Poole-05.pdf
Bacterial defenses against oxidants: mechanistic features of cysteine-based peroxidases and their flavoprotein reductases.
AhpF is not the universal AhpC regeneration architecture; multiple-protein thioredoxin and related systems occur in AhpF-deficient organisms.
In many AhpF-deficient organisms, the NAD(P)H-dependent recycling of AhpC or other Prxs is mediated by at least two proteins
PMID:18084895
Peroxiredoxin systems in mycobacteria.
The mycobacterial review explicitly distinguishes AhpD and TrxC as alternate AhpC reductants.
AhpC can be reduced by AhpD, a CXXC-motif-containing protein, or by one of the mycobacterial thioredoxins, TrxC.
PMID:34258640
Relevance of peroxiredoxins in pathogenic microorganisms.
AhpC/Prx1 is one of six mechanistically diverse peroxiredoxin classes, supporting exclusion of Tpx, BCP and AhpE from this module.
Prx are very diverse and are classified into six different classes (Prx1-AhpC, BCP-PrxQ, Tpx, Prx5, Prx6, and AhpE)
PMID:38899743
From ubiquity to specificity: The diverse functions of bacterial thioredoxin systems.
Thioredoxin systems specialize their cofactors and clients during bacterial evolution; a shared reductase family is not evidence for arbitrary partner substitution.
This evolution can be characterized by the multiplication of the systems and by the specialization of cofactors or targets
PMID:11717276
Alkyl hydroperoxide reductase is the primary scavenger of endogenous hydrogen peroxide in Escherichia coli.
Native E. coli experiments identify AhpCF as a major low-H2O2 scavenger under tested conditions, with catalase important at higher challenge.
Ahp is kinetically a more efficient scavenger of trace H(2)O(2) than is catalase
Warnings
7Nodes
0Parts
1Variant Sets
6Variants
16Annotons
10Connections

Derived QC

Recommended-field compliance

86.4% recommended fields populated
  • references[18] · findings (0/1)
  • references[19] · findings (0/1)
  • references[20] · findings (0/1)

Module deep research

✗ none found

No MODULE:bacterial_alkyl_hydroperoxide_reductase deep-research report alongside the module YAML.

Leaf nodes lacking representative members

✓ every leaf node grounds to a representative protein.

Template conformance

✓ every declared conforms_to bundle matches its template motif.

Function consistency and core coverage

16 gene-function check(s) reflected in core functions · 0 conflict(s) · 9 evidence or coverage gap(s) (32 comparison(s))

Retained noncore functions are reported separately; they do not require promotion to core functions. Support from representative genes does not establish conservation across the whole family. Missing reviews or identifiers leave a claim unverified.

AnnotonParticipantFunctionAssessment
ahpf_nadh_dependent_peroxiredoxin_reductase ahpF
UniProtKB:P35340
Gene 		protein-disulfide reductase [NAD(P)H] activity
GO:0047134 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
ahpc_peroxiredoxin ahpC
UniProtKB:P0AE08
Gene 		peroxiredoxin activity
GO:0051920 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
salty_ahpf ahpF
UniProtKB:P19480
Gene 		protein-disulfide reductase [NAD(P)H] activity
GO:0047134 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
salty_ahpc ahpC
UniProtKB:P0A251
Gene 		peroxiredoxin activity
GO:0051920 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
bacsu_ahpf ahpF
UniProtKB:P42974
Gene 		protein-disulfide reductase [NAD(P)H] activity
GO:0047134 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
bacsu_ahpc ahpC
UniProtKB:P80239
Gene 		peroxiredoxin activity
GO:0051920 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
helpy_trxr trxB
UniProtKB:P56431
Gene 		thioredoxin-disulfide reductase (NADPH) activity
GO:0004791 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
helpy_trx trxA
UniProtKB:P66928
Gene 		protein-disulfide reductase activity
GO:0015035 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
helpy_trx_ahpc ahpC
UniProtKB:P21762
Gene 		thioredoxin-dependent peroxiredoxin activity
GO:0140824 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
myctu_trxr trxB
UniProtKB:P9WHH1
Gene 		thioredoxin-disulfide reductase (NADPH) activity
GO:0004791 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
myctu_trx trxA
UniProtKB:P9WG67
Gene 		protein-disulfide reductase activity
GO:0015035 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
myctu_trx_ahpc ahpC
UniProtKB:P9WQB7
Gene 		thioredoxin-dependent peroxiredoxin activity
GO:0140824 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
myctu_lpd lpdC
UniProtKB:P9WHH9
Gene 		dihydrolipoyl dehydrogenase (NADH) activity
GO:0004148 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
myctu_dlat dlaT
UniProtKB:P9WIS7
Gene 		disulfide oxidoreductase activity
GO:0015036 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
myctu_ahpd ahpD
UniProtKB:P9WQB5
Gene 		disulfide oxidoreductase activity
GO:0015036 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
myctu_lipoyl_ahpc ahpC
UniProtKB:P9WQB7
Gene 		peroxiredoxin activity
GO:0051920 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
ahpf_nadh_dependent_peroxiredoxin_reductase ECOLI ahpF classification; exact product defines the activity
PANTHER:PTHR48105
Family 		protein-disulfide reductase [NAD(P)H] activity
GO:0047134 		Family Function Unreviewed
The family review has no applicable adjudication supporting or excluding GO:0047134.
ahpc_peroxiredoxin ECOLI ahpC classification; exact product defines the activity
PANTHER:PTHR10681:SF121
Family 		peroxiredoxin activity
GO:0051920 		Family Supported
Family review supports GO:0140824 FAMILY_WIDE. Asserted by glutathione_thioredoxin_redox_systems; accepted by S. cerevisiae TSA1/TSA2, S. pombe tpx1 and human PRDX4.
salty_ahpf SALTY ahpF classification; exact product defines the activity
PANTHER:PTHR48105
Family 		protein-disulfide reductase [NAD(P)H] activity
GO:0047134 		Family Function Unreviewed
The family review has no applicable adjudication supporting or excluding GO:0047134.
salty_ahpc SALTY ahpC classification; exact product defines the activity
PANTHER:PTHR10681:SF121
Family 		peroxiredoxin activity
GO:0051920 		Family Supported
Family review supports GO:0140824 FAMILY_WIDE. Asserted by glutathione_thioredoxin_redox_systems; accepted by S. cerevisiae TSA1/TSA2, S. pombe tpx1 and human PRDX4.
bacsu_ahpf BACSU ahpF classification; exact product defines the activity
PANTHER:PTHR48105
Family 		protein-disulfide reductase [NAD(P)H] activity
GO:0047134 		Family Function Unreviewed
The family review has no applicable adjudication supporting or excluding GO:0047134.
bacsu_ahpc BACSU ahpC classification; exact product defines the activity
PANTHER:PTHR10681:SF121
Family 		peroxiredoxin activity
GO:0051920 		Family Supported
Family review supports GO:0140824 FAMILY_WIDE. Asserted by glutathione_thioredoxin_redox_systems; accepted by S. cerevisiae TSA1/TSA2, S. pombe tpx1 and human PRDX4.
helpy_trxr HELPY trxB classification; exact product defines the activity
PANTHER:PTHR48105
Family 		thioredoxin-disulfide reductase (NADPH) activity
GO:0004791 		Family Scope Restricted
GO:0004791 is SUBFAMILY_ONLY; this family grounding does not establish the allowed subfamily scope. Asserted by glutathione_thioredoxin_redox_systems; accepted by TRR1, TRR2 and trr1.
helpy_trx HELPY trxA classification; exact product defines the activity
PANTHER:PTHR45663:SF11
Family 		protein-disulfide reductase activity
GO:0015035 		Family Review Missing
No supported structured family review is available for PANTHER:PTHR45663:SF11.
helpy_trx_ahpc HELPY ahpC classification; exact product defines the activity
PANTHER:PTHR10681:SF128
Family 		thioredoxin-dependent peroxiredoxin activity
GO:0140824 		Family Supported
Family review supports GO:0140824 FAMILY_WIDE. Asserted by glutathione_thioredoxin_redox_systems; accepted by S. cerevisiae TSA1/TSA2, S. pombe tpx1 and human PRDX4.
myctu_trxr MYCTU trxB classification; exact product defines the activity
PANTHER:PTHR48105
Family 		thioredoxin-disulfide reductase (NADPH) activity
GO:0004791 		Family Scope Restricted
GO:0004791 is SUBFAMILY_ONLY; this family grounding does not establish the allowed subfamily scope. Asserted by glutathione_thioredoxin_redox_systems; accepted by TRR1, TRR2 and trr1.
myctu_trx MYCTU trxA classification; exact product defines the activity
PANTHER:PTHR45663:SF11
Family 		protein-disulfide reductase activity
GO:0015035 		Family Review Missing
No supported structured family review is available for PANTHER:PTHR45663:SF11.
myctu_trx_ahpc MYCTU ahpC classification; exact product defines the activity
PANTHER:PTHR10681:SF121
Family 		thioredoxin-dependent peroxiredoxin activity
GO:0140824 		Family Supported
Family review supports GO:0140824 FAMILY_WIDE. Asserted by glutathione_thioredoxin_redox_systems; accepted by S. cerevisiae TSA1/TSA2, S. pombe tpx1 and human PRDX4.
myctu_lpd MYCTU lpdC classification; exact product defines the activity
PANTHER:PTHR22912:SF217
Family 		dihydrolipoyl dehydrogenase (NADH) activity
GO:0004148 		Family Supported
Family review supports GO:0004148 for PANTHER:PTHR22912:SF217. The E3 subfamilies, not the divergent SthA transhydrogenase. SF219 is included on the basis of its independently mapped AcoL representative, the native sequence-based E3 assignment in PMID:10368162 and the conserved catalytic architecture. This extends chemistry scope, not a requirement that all E3 paralogs serve the same physiological complexes. No new PAINT node is inferred.
myctu_dlat MYCTU dlaT classification; exact product defines the activity
PANTHER:PTHR43178:SF5
Family 		disulfide oxidoreductase activity
GO:0015036 		Family Function Unreviewed
The family review has no applicable adjudication supporting or excluding GO:0015036.
myctu_ahpd MYCTU ahpD classification; exact product defines the activity
PANTHER:PTHR33930:SF7
Family 		disulfide oxidoreductase activity
GO:0015036 		Family Review Missing
No supported structured family review is available for PANTHER:PTHR33930:SF7.
myctu_lipoyl_ahpc MYCTU ahpC classification; exact product defines the activity
PANTHER:PTHR10681:SF121
Family 		peroxiredoxin activity
GO:0051920 		Family Supported
Family review supports GO:0140824 FAMILY_WIDE. Asserted by glutathione_thioredoxin_redox_systems; accepted by S. cerevisiae TSA1/TSA2, S. pombe tpx1 and human PRDX4.

Gene-review completeness (15/15 grounded genes reviewed)

6 complete review(s) · 0 with deep research · 0 missing review · 15 reviewed but lacking deep research

Gene Review Complete Deep research
ahpC P0A251 ✓ ✓ ✗
ahpC P0AE08 ✓ 29/33 ✗
ahpC P21762 ✓ ✓ ✗
ahpC P80239 ✓ ✓ ✗
ahpC P9WQB7 ✓ 29/30 ✗
ahpD P9WQB5 ✓ 15/16 ✗
ahpF P19480 ✓ ✓ ✗
ahpF P35340 ✓ ✓ ✗
ahpF P42974 ✓ 15/16 ✗
dlaT P9WIS7 ✓ 16/17 ✗
lpdC P9WHH9 ✓ 24/27 ✗
trxA P66928 ✓ ✓ ✗
trxA P9WG67 ✓ 21/22 ✗
trxB P56431 ✓ 5/6 ✗
trxB P9WHH1 ✓ 16/17 ✗

Details

Context
BacteriaNCBITaxon:2
A sampled native AhpC system has a functional reducing chain and an accepted peroxide substrate
Bacterial AhpC peroxide reduction with characterized regeneration chainsMolecular Functionbacterial_alkyl_hydroperoxide_reductase

At least one complete organism-coherent implementation supplies peroxide reduction and regeneration of AhpC. These alternatives define named biochemical capabilities, not a complete cellular stress-defense network, minimal growth sufficiency, or universal bacterial distribution. Molecular oxygen is not a stoichiometric substrate; anaerobic coupled assays are valid.

peroxiredoxin activityGO:0051920
Context
BacteriaNCBITaxon:2
A sampled native AhpC system has a functional reducing chain and an accepted peroxide substrate

Scope excludes Tpx/BCP/AhpE and other peroxiredoxin families, catalases, superoxide dismutases, glutathione pathways, general thioredoxin clients and upstream PDH carbon metabolism. The Eukaryota-scoped glutathione_thioredoxin_redox_systems module is unchanged. Exact gene-product selectors prevent broad PANTHER groups or mixed-species donors from satisfying a route. Verified PANTHER labels containing mitochondrial or unrelated representative names are classification labels, not functional/localization transfers. Original E. coli leaf ids are retained for corpus references.

Variant set: Characterized native-protein regeneration architectures by Organism and experimentally supported electron-donor chain (One Or More)
ECOLI AhpC/AhpF implementationMolecular Functionecoli_ahpc_ahpf

The named pair is one native implementation, not a claim that it alone defines cellular peroxide survival. Purified same-species pairing and native/recombinant evidence support the electron-transfer step.

Context
Escherichia coli K-12NCBITaxon:83333
Functional proteins, appropriate reducing equivalents and an accepted peroxide substrate are available
PMID:28270505
Essential role of the flexible linker on the conformational equilibrium of bacterial peroxiredoxin reductase for effective regeneration of peroxiredoxin.
Purified E. coli AhpF linker variants impair electron transfer and AhpC-supported peroxide turnover.
The mutants also exhibited a decrease in H2O2 reduction by the AhpF-AhpC ensemble.

Annotons

ECOLI ahpF: protein-disulfide reductase [NAD(P)H] activity
ahpf_nadh_dependent_peroxiredoxin_reductase
Participant: Gene Product: ahpF
Gene Product:
ahpFUniProtKB:P35340
Family:
ECOLI ahpF classification; exact product defines the activityPANTHER:PTHR48105
Representative Members: ahpFUniProtKB:P35340

Function

protein-disulfide reductase [NAD(P)H] activityGO:0047134
Substrates: oxidized ECOLI AhpC NADH
Products: reduced ECOLI AhpC NAD+
Cofactors: FAD

Processes

cellular oxidant detoxificationGO:0098869

AhpF accepts reducing equivalents through FAD and transfers them through its disulfide centers to AhpC. NADH is the characterized preferred donor in the classical system; the term does not assert equal NADPH efficiency.

PMID:28270505
Essential role of the flexible linker on the conformational equilibrium of bacterial peroxiredoxin reductase for effective regeneration of peroxiredoxin.
Purified E. coli AhpF linker variants impair electron transfer and AhpC-supported peroxide turnover.
The mutants also exhibited a decrease in H2O2 reduction by the AhpF-AhpC ensemble.
url:https://scb.wfu.edu/Poole-files/ABB-Poole-05.pdf
Bacterial defenses against oxidants: mechanistic features of cysteine-based peroxidases and their flavoprotein reductases.
AhpF is not the universal AhpC regeneration architecture; multiple-protein thioredoxin and related systems occur in AhpF-deficient organisms.
In many AhpF-deficient organisms, the NAD(P)H-dependent recycling of AhpC or other Prxs is mediated by at least two proteins
ECOLI ahpC: peroxiredoxin activity
ahpc_peroxiredoxin
Participant: Gene Product: ahpC
Gene Product:
ahpCUniProtKB:P0AE08
Family:
ECOLI ahpC classification; exact product defines the activityPANTHER:PTHR10681:SF121
Representative Members: ahpCUniProtKB:P0AE08

Function

peroxiredoxin activityGO:0051920
Substrates: reduced ECOLI AhpC hydrogen peroxide or accepted organic hydroperoxide
Products: oxidized ECOLI AhpC water or corresponding alcohol

Processes

cellular oxidant detoxificationGO:0098869

AhpC attacks peroxide with its peroxidatic cysteine and is regenerated by the matching AhpF. Redox-dependent oligomers are not encoded as fixed stoichiometry.

PMID:28270505
Essential role of the flexible linker on the conformational equilibrium of bacterial peroxiredoxin reductase for effective regeneration of peroxiredoxin.
Purified E. coli AhpF linker variants impair electron transfer and AhpC-supported peroxide turnover.
The mutants also exhibited a decrease in H2O2 reduction by the AhpF-AhpC ensemble.

Connections

AhpF reduction supplies reduced AhpC for peroxide attack.
PMID:28270505
Essential role of the flexible linker on the conformational equilibrium of bacterial peroxiredoxin reductase for effective regeneration of peroxiredoxin.
Purified E. coli AhpF linker variants impair electron transfer and AhpC-supported peroxide turnover.
The mutants also exhibited a decrease in H2O2 reduction by the AhpF-AhpC ensemble.
SALTY AhpC/AhpF implementationMolecular Functionsalty_ahpc_ahpf

The named pair is one native implementation, not a claim that it alone defines cellular peroxide survival. Purified same-species pairing and native/recombinant evidence support the electron-transfer step.

Context
Salmonella enterica subsp. enterica serovar Typhimurium str. LT2NCBITaxon:99287
Functional proteins, appropriate reducing equivalents and an accepted peroxide substrate are available
PMID:8555198
Flavin-dependent alkyl hydroperoxide reductase from Salmonella typhimurium. 1. Purification and enzymatic activities of overexpressed AhpF and AhpC proteins.
Salmonella AhpF/AhpC reduce peroxide in a coupled purified system; native and recombinant preparations behaved alike.
All assays gave identical results whether overexpressed S. typhimurium proteins from E. coli or proteins isolated directly from S. typhimurium were used.

Annotons

SALTY ahpF: protein-disulfide reductase [NAD(P)H] activity
salty_ahpf
Participant: Gene Product: ahpF
Gene Product:
ahpFUniProtKB:P19480
Family:
SALTY ahpF classification; exact product defines the activityPANTHER:PTHR48105
Representative Members: ahpFUniProtKB:P19480

Function

protein-disulfide reductase [NAD(P)H] activityGO:0047134
Substrates: oxidized SALTY AhpC NADH
Products: reduced SALTY AhpC NAD+
Cofactors: FAD

Processes

cellular oxidant detoxificationGO:0098869

AhpF accepts reducing equivalents through FAD and transfers them through its disulfide centers to AhpC. NADH is the characterized preferred donor in the classical system; the term does not assert equal NADPH efficiency.

PMID:8555198
Flavin-dependent alkyl hydroperoxide reductase from Salmonella typhimurium. 1. Purification and enzymatic activities of overexpressed AhpF and AhpC proteins.
Salmonella AhpF/AhpC reduce peroxide in a coupled purified system; native and recombinant preparations behaved alike.
All assays gave identical results whether overexpressed S. typhimurium proteins from E. coli or proteins isolated directly from S. typhimurium were used.
url:https://scb.wfu.edu/Poole-files/ABB-Poole-05.pdf
Bacterial defenses against oxidants: mechanistic features of cysteine-based peroxidases and their flavoprotein reductases.
AhpF is not the universal AhpC regeneration architecture; multiple-protein thioredoxin and related systems occur in AhpF-deficient organisms.
In many AhpF-deficient organisms, the NAD(P)H-dependent recycling of AhpC or other Prxs is mediated by at least two proteins
SALTY ahpC: peroxiredoxin activity
salty_ahpc
Participant: Gene Product: ahpC
Gene Product:
ahpCUniProtKB:P0A251
Family:
SALTY ahpC classification; exact product defines the activityPANTHER:PTHR10681:SF121
Representative Members: ahpCUniProtKB:P0A251

Function

peroxiredoxin activityGO:0051920
Substrates: reduced SALTY AhpC hydrogen peroxide or accepted organic hydroperoxide
Products: oxidized SALTY AhpC water or corresponding alcohol

Processes

cellular oxidant detoxificationGO:0098869

AhpC attacks peroxide with its peroxidatic cysteine and is regenerated by the matching AhpF. Redox-dependent oligomers are not encoded as fixed stoichiometry.

PMID:8555198
Flavin-dependent alkyl hydroperoxide reductase from Salmonella typhimurium. 1. Purification and enzymatic activities of overexpressed AhpF and AhpC proteins.
Salmonella AhpF/AhpC reduce peroxide in a coupled purified system; native and recombinant preparations behaved alike.
All assays gave identical results whether overexpressed S. typhimurium proteins from E. coli or proteins isolated directly from S. typhimurium were used.

Connections

salty_ahpf -> salty_ahpc Provides Input For
AhpF reduction supplies reduced AhpC for peroxide attack.
PMID:8555198
Flavin-dependent alkyl hydroperoxide reductase from Salmonella typhimurium. 1. Purification and enzymatic activities of overexpressed AhpF and AhpC proteins.
Salmonella AhpF/AhpC reduce peroxide in a coupled purified system; native and recombinant preparations behaved alike.
All assays gave identical results whether overexpressed S. typhimurium proteins from E. coli or proteins isolated directly from S. typhimurium were used.
BACSU AhpC/AhpF implementationMolecular Functionbacsu_ahpc_ahpf

The named pair is one native implementation, not a claim that it alone defines cellular peroxide survival. Native operon and mutant physiology support the implementation; exact pair chemistry is an architecture- and orthology-based inference from characterized AhpF/AhpC systems. H2O2 hyper-resistance of the mutant reflects compensatory regulation and does not negate peroxide chemistry.

Context
Bacillus subtilis subsp. subtilis str. 168NCBITaxon:224308
Functional proteins, appropriate reducing equivalents and an accepted peroxide substrate are available
PMID:8932314
General and oxidative stress responses in Bacillus subtilis: cloning, expression, and mutation of the alkyl hydroperoxide reductase operon.
Native Bacillus operon and mutant physiology support an AhpC/AhpF peroxide-defense implementation, with compensation and growth-stage limits.
the ahpC mutant was resistant to hydrogen peroxide because of the derepression of the peroxide regulon

Annotons

BACSU ahpF: protein-disulfide reductase [NAD(P)H] activity
bacsu_ahpf
Participant: Gene Product: ahpF
Gene Product:
ahpFUniProtKB:P42974
Family:
BACSU ahpF classification; exact product defines the activityPANTHER:PTHR48105
Representative Members: ahpFUniProtKB:P42974

Function

protein-disulfide reductase [NAD(P)H] activityGO:0047134
Substrates: oxidized BACSU AhpC NADH
Products: reduced BACSU AhpC NAD+
Cofactors: FAD

Processes

cellular oxidant detoxificationGO:0098869

AhpF accepts reducing equivalents through FAD and transfers them through its disulfide centers to AhpC. NADH is the characterized preferred donor in the classical system; the term does not assert equal NADPH efficiency.

PMID:8932314
General and oxidative stress responses in Bacillus subtilis: cloning, expression, and mutation of the alkyl hydroperoxide reductase operon.
Native Bacillus operon and mutant physiology support an AhpC/AhpF peroxide-defense implementation, with compensation and growth-stage limits.
the ahpC mutant was resistant to hydrogen peroxide because of the derepression of the peroxide regulon
url:https://scb.wfu.edu/Poole-files/ABB-Poole-05.pdf
Bacterial defenses against oxidants: mechanistic features of cysteine-based peroxidases and their flavoprotein reductases.
AhpF is not the universal AhpC regeneration architecture; multiple-protein thioredoxin and related systems occur in AhpF-deficient organisms.
In many AhpF-deficient organisms, the NAD(P)H-dependent recycling of AhpC or other Prxs is mediated by at least two proteins
BACSU ahpC: peroxiredoxin activity
bacsu_ahpc
Participant: Gene Product: ahpC
Gene Product:
ahpCUniProtKB:P80239
Family:
BACSU ahpC classification; exact product defines the activityPANTHER:PTHR10681:SF121
Representative Members: ahpCUniProtKB:P80239

Function

peroxiredoxin activityGO:0051920
Substrates: reduced BACSU AhpC hydrogen peroxide or accepted organic hydroperoxide
Products: oxidized BACSU AhpC water or corresponding alcohol

Processes

cellular oxidant detoxificationGO:0098869

AhpC attacks peroxide with its peroxidatic cysteine and is regenerated by the matching AhpF. Redox-dependent oligomers are not encoded as fixed stoichiometry.

PMID:8932314
General and oxidative stress responses in Bacillus subtilis: cloning, expression, and mutation of the alkyl hydroperoxide reductase operon.
Native Bacillus operon and mutant physiology support an AhpC/AhpF peroxide-defense implementation, with compensation and growth-stage limits.
the ahpC mutant was resistant to hydrogen peroxide because of the derepression of the peroxide regulon

Connections

bacsu_ahpf -> bacsu_ahpc Provides Input For
AhpF reduction supplies reduced AhpC for peroxide attack.
PMID:8932314
General and oxidative stress responses in Bacillus subtilis: cloning, expression, and mutation of the alkyl hydroperoxide reductase operon.
Native Bacillus operon and mutant physiology support an AhpC/AhpF peroxide-defense implementation, with compensation and growth-stage limits.
the ahpC mutant was resistant to hydrogen peroxide because of the derepression of the peroxide regulon
HELPY thioredoxin-dependent AhpC implementationMolecular Functionhelpy_thioredoxin_ahpc

Native cloned H. pylori 26695 TrxR/Trx1/AhpC pairing is supported, while detailed peroxide constants in the paper use E. coli TrxR. Trx2 and Salmonella AhpF do not replace Trx1/native regeneration in the reported tests.

Context
Helicobacter pylori 26695NCBITaxon:85962
Functional proteins, appropriate reducing equivalents and an accepted peroxide substrate are available
PMID:11222594
Essential thioredoxin-dependent peroxiredoxin system from Helicobacter pylori: genetic and kinetic characterization.
H. pylori AhpC is regenerated by its thioredoxin system rather than the Salmonella AhpF used in a comparator assay.
Instead, homologues of Escherichia coli thioredoxin (Trx) reductase (TrxR, HP0825) and Trx (Trx1, HP0824) formed a reductase system for H. pylori AhpC.
url:https://scb.wfu.edu/Poole-files/Baker_Hpylori.pdf
Essential thioredoxin-dependent peroxiredoxin system from Helicobacter pylori: genetic and kinetic characterization.
Native H. pylori TrxR does not use NADH in the tested donor-substitution experiment.
In TrxR-Trx1-insulin experiments in which NADPH was replaced with NADH, no decrease in the NADH A 340 was observed

Annotons

HELPY trxB: thioredoxin-disulfide reductase (NADPH) activity
helpy_trxr
Participant: Gene Product: trxB
Gene Product:
trxBUniProtKB:P56431
Family:
HELPY trxB classification; exact product defines the activityPANTHER:PTHR48105
Representative Members: trxBUniProtKB:P56431

Function

thioredoxin-disulfide reductase (NADPH) activityGO:0004791
Substrates: NADPH oxidized HELPY thioredoxin
Products: NADP+ reduced HELPY thioredoxin
Cofactors: FAD

Processes

cellular oxidant detoxificationGO:0098869

The FAD-dependent thioredoxin reductase regenerates the exact thioredoxin partner with NADPH; other clients are outside the boundary.

PMID:11222594
Essential thioredoxin-dependent peroxiredoxin system from Helicobacter pylori: genetic and kinetic characterization.
H. pylori AhpC is regenerated by its thioredoxin system rather than the Salmonella AhpF used in a comparator assay.
Instead, homologues of Escherichia coli thioredoxin (Trx) reductase (TrxR, HP0825) and Trx (Trx1, HP0824) formed a reductase system for H. pylori AhpC.
HELPY trxA: protein-disulfide reductase activity
helpy_trx
Participant: Gene Product: trxA
Gene Product:
trxAUniProtKB:P66928
Family:
HELPY trxA classification; exact product defines the activityPANTHER:PTHR45663:SF11
Representative Members: trxAUniProtKB:P66928

Function

protein-disulfide reductase activityGO:0015035
Substrates: reduced HELPY thioredoxin oxidized HELPY AhpC
Products: oxidized HELPY thioredoxin reduced HELPY AhpC

Processes

cellular oxidant detoxificationGO:0098869

The small thioredoxin Trx1 (HP0824) reduces the AhpC disulfide in the tested H. pylori TrxR–Trx1–AhpC system.

PMID:11222594
Essential thioredoxin-dependent peroxiredoxin system from Helicobacter pylori: genetic and kinetic characterization.
H. pylori AhpC is regenerated by its thioredoxin system rather than the Salmonella AhpF used in a comparator assay.
Instead, homologues of Escherichia coli thioredoxin (Trx) reductase (TrxR, HP0825) and Trx (Trx1, HP0824) formed a reductase system for H. pylori AhpC.
HELPY ahpC: thioredoxin-dependent peroxiredoxin activity
helpy_trx_ahpc
Participant: Gene Product: ahpC
Gene Product:
ahpCUniProtKB:P21762
Family:
HELPY ahpC classification; exact product defines the activityPANTHER:PTHR10681:SF128
Representative Members: ahpCUniProtKB:P21762

Function

thioredoxin-dependent peroxiredoxin activityGO:0140824
Substrates: reduced HELPY AhpC hydrogen peroxide or accepted organic hydroperoxide
Products: oxidized HELPY AhpC water or corresponding alcohol

Processes

cellular oxidant detoxificationGO:0098869

AhpC performs thioredoxin-supported peroxide reduction. A shared thioredoxin family does not make every paralog an interchangeable donor.

PMID:11222594
Essential thioredoxin-dependent peroxiredoxin system from Helicobacter pylori: genetic and kinetic characterization.
H. pylori AhpC is regenerated by its thioredoxin system rather than the Salmonella AhpF used in a comparator assay.
Instead, homologues of Escherichia coli thioredoxin (Trx) reductase (TrxR, HP0825) and Trx (Trx1, HP0824) formed a reductase system for H. pylori AhpC.

Connections

helpy_trxr -> helpy_trx Provides Input For
NADPH-dependent TrxR regenerates the reduced thioredoxin used by the next step.
PMID:11222594
Essential thioredoxin-dependent peroxiredoxin system from Helicobacter pylori: genetic and kinetic characterization.
H. pylori AhpC is regenerated by its thioredoxin system rather than the Salmonella AhpF used in a comparator assay.
Instead, homologues of Escherichia coli thioredoxin (Trx) reductase (TrxR, HP0825) and Trx (Trx1, HP0824) formed a reductase system for H. pylori AhpC.
helpy_trx -> helpy_trx_ahpc Provides Input For
The matched thioredoxin regenerates reduced AhpC.
PMID:11222594
Essential thioredoxin-dependent peroxiredoxin system from Helicobacter pylori: genetic and kinetic characterization.
H. pylori AhpC is regenerated by its thioredoxin system rather than the Salmonella AhpF used in a comparator assay.
Instead, homologues of Escherichia coli thioredoxin (Trx) reductase (TrxR, HP0825) and Trx (Trx1, HP0824) formed a reductase system for H. pylori AhpC.
MYCTU thioredoxin-dependent AhpC implementationMolecular Functionmyctu_thioredoxin_ahpc

The Mtb TrxR/TrxC/AhpC chain is demonstrated in biochemical assays. BCG recombinant interaction/turnover corroborates its mechanism with explicit strain limits; native H37Rv route predominance and exclusivity are not established.

Context
Mycobacterium tuberculosis H37RvNCBITaxon:83332
Functional proteins, appropriate reducing equivalents and an accepted peroxide substrate are available
PMID:14871480
Multiple thioredoxin-mediated routes to detoxify hydroperoxides in Mycobacterium tuberculosis.
Mtb TrxC plus thioredoxin reductase supplies a distinct NADPH-linked AhpC regeneration route.
NADPH-driven hydroperoxide reduction by AhpC that is mediated by thioredoxin reductase and thioredoxin C
PMID:28698569
AhpC of the mycobacterial antioxidant defense system and its interaction with its reducing partner Thioredoxin-C.
BCG recombinant TrxB2/TrxC supports AhpC peroxide turnover and NMR detects the TrxC–AhpC interface; this corroborates but is not a native H37Rv experiment.
This demonstrates the binding of MbTrxC with MbAhpC.
PMID:27249779
Mycobacterium tuberculosis Thioredoxin Reductase Is Essential for Thiol Redox Homeostasis but Plays a Minor Role in Antioxidant Defense.
Native conditional TrxB2 depletion distinguishes thiol-specific oxidant defense from the tested peroxide, RNS and plumbagin phenotypes; the biochemical AhpC chain is not thereby made obligatory.
partial inhibition of TrxB2 did not affect Mtb’s susceptibility to growth inhibition or killing by plumbagin, a superoxide generator

Annotons

MYCTU trxB: thioredoxin-disulfide reductase (NADPH) activity
myctu_trxr
Participant: Gene Product: trxB
Gene Product:
trxBUniProtKB:P9WHH1
Family:
MYCTU trxB classification; exact product defines the activityPANTHER:PTHR48105
Representative Members: trxBUniProtKB:P9WHH1

Function

thioredoxin-disulfide reductase (NADPH) activityGO:0004791
Substrates: NADPH oxidized MYCTU thioredoxin
Products: NADP+ reduced MYCTU thioredoxin
Cofactors: FAD

Processes

cellular oxidant detoxificationGO:0098869

The FAD-dependent thioredoxin reductase regenerates the exact thioredoxin partner with NADPH; other clients are outside the boundary.

PMID:14871480
Multiple thioredoxin-mediated routes to detoxify hydroperoxides in Mycobacterium tuberculosis.
Mtb TrxC plus thioredoxin reductase supplies a distinct NADPH-linked AhpC regeneration route.
NADPH-driven hydroperoxide reduction by AhpC that is mediated by thioredoxin reductase and thioredoxin C
MYCTU trxA: protein-disulfide reductase activity
myctu_trx
Participant: Gene Product: trxA
Gene Product:
trxAUniProtKB:P9WG67
Family:
MYCTU trxA classification; exact product defines the activityPANTHER:PTHR45663:SF11
Representative Members: trxAUniProtKB:P9WG67

Function

protein-disulfide reductase activityGO:0015035
Substrates: reduced MYCTU thioredoxin oxidized MYCTU AhpC
Products: oxidized MYCTU thioredoxin reduced MYCTU AhpC

Processes

cellular oxidant detoxificationGO:0098869

The small thioredoxin reduces the AhpC disulfide. For MYCTU, the official trxA/Rv3914 protein is literature TrxC, not the separate Rv1470 protein called TrxA in older papers.

PMID:14871480
Multiple thioredoxin-mediated routes to detoxify hydroperoxides in Mycobacterium tuberculosis.
Mtb TrxC plus thioredoxin reductase supplies a distinct NADPH-linked AhpC regeneration route.
NADPH-driven hydroperoxide reduction by AhpC that is mediated by thioredoxin reductase and thioredoxin C
MYCTU ahpC: thioredoxin-dependent peroxiredoxin activity
myctu_trx_ahpc
Participant: Gene Product: ahpC
Gene Product:
ahpCUniProtKB:P9WQB7
Family:
MYCTU ahpC classification; exact product defines the activityPANTHER:PTHR10681:SF121
Representative Members: ahpCUniProtKB:P9WQB7

Function

thioredoxin-dependent peroxiredoxin activityGO:0140824
Substrates: reduced MYCTU AhpC hydrogen peroxide or accepted organic hydroperoxide
Products: oxidized MYCTU AhpC water or corresponding alcohol

Processes

cellular oxidant detoxificationGO:0098869

AhpC performs thioredoxin-supported peroxide reduction. A shared thioredoxin family does not make every paralog an interchangeable donor.

PMID:14871480
Multiple thioredoxin-mediated routes to detoxify hydroperoxides in Mycobacterium tuberculosis.
Mtb TrxC plus thioredoxin reductase supplies a distinct NADPH-linked AhpC regeneration route.
NADPH-driven hydroperoxide reduction by AhpC that is mediated by thioredoxin reductase and thioredoxin C

Connections

myctu_trxr -> myctu_trx Provides Input For
NADPH-dependent TrxR regenerates the reduced thioredoxin used by the next step.
PMID:14871480
Multiple thioredoxin-mediated routes to detoxify hydroperoxides in Mycobacterium tuberculosis.
Mtb TrxC plus thioredoxin reductase supplies a distinct NADPH-linked AhpC regeneration route.
NADPH-driven hydroperoxide reduction by AhpC that is mediated by thioredoxin reductase and thioredoxin C
myctu_trx -> myctu_trx_ahpc Provides Input For
The matched thioredoxin regenerates reduced AhpC.
PMID:14871480
Multiple thioredoxin-mediated routes to detoxify hydroperoxides in Mycobacterium tuberculosis.
Mtb TrxC plus thioredoxin reductase supplies a distinct NADPH-linked AhpC regeneration route.
NADPH-driven hydroperoxide reduction by AhpC that is mediated by thioredoxin reductase and thioredoxin C
Mtb lipoyl-DlaT/AhpD-dependent AhpC implementationMolecular Functionmyctu_lipoyl_ahpc

The identified four-protein route represents a biochemical regeneration chain, not a uniquely required peroxide-survival genotype or a fixed-stoichiometry stable complex. Native Lpd/DlaT genetics also perturb carbon metabolism. The 2004 AhpC–AhpD contact assay uses bovine DHLDH/free lipoamide upstream, distinguished from the native-protein relay.

Context
Mycobacterium tuberculosis H37RvNCBITaxon:83332
Functional proteins, appropriate reducing equivalents and an accepted peroxide substrate are available
PMID:11799204
Metabolic enzymes of mycobacteria linked to antioxidant defense by a thioredoxin-like protein.
The Mtb proteins define a lipoyl-mediated electron relay linking Lpd to AhpC through DlaT and AhpD.
The peroxiredoxin alkyl hydroperoxide reductase (AhpC) is linked to Lpd and SucB by an adaptor protein, AhpD.
PMID:21238944
Virulence of Mycobacterium tuberculosis depends on lipoamide dehydrogenase, a member of three multienzyme complexes.
Native Lpd perturbation does not establish an obligatory peroxide-survival pathway: the tested mutant is more H2O2-resistant.
Mtb lacking lpdC was more resistant than WT and complemented strains

Annotons

MYCTU lpdC: dihydrolipoyl dehydrogenase (NADH) activity
myctu_lpd
Participant: Gene Product: lpdC
Gene Product:
lpdCUniProtKB:P9WHH9
Family:
MYCTU lpdC classification; exact product defines the activityPANTHER:PTHR22912:SF217
Representative Members: lpdCUniProtKB:P9WHH9

Function

dihydrolipoyl dehydrogenase (NADH) activityGO:0004148
Substrates: NADH oxidized lipoyl-DlaT
Products: NAD+ reduced dihydrolipoyl-DlaT
Cofactors: FAD

Processes

cellular oxidant detoxificationGO:0098869

Lpd catalyses NADH-dependent reduction of lipoyl-DlaT in the reductive direction of its reversible E3 reaction; its oxidative PDH function lies outside this module.

PMID:11799204
Metabolic enzymes of mycobacteria linked to antioxidant defense by a thioredoxin-like protein.
The Mtb proteins define a lipoyl-mediated electron relay linking Lpd to AhpC through DlaT and AhpD.
The peroxiredoxin alkyl hydroperoxide reductase (AhpC) is linked to Lpd and SucB by an adaptor protein, AhpD.
PMID:16045627
Mycobacterium tuberculosis appears to lack alpha-ketoglutarate dehydrogenase and encodes pyruvate dehydrogenase in widely separated genes.
DlaT is experimentally the PDH E2 partner of Lpd, distinct from an oxoglutarate-dehydrogenase SucB assignment.
Finally, recombinant AceE, DlaT and Lpd, although encoded by genes that are widely separated on the chromosome, reconstituted PDH in vitro with Km values typical of bacterial PDH complexes.
MYCTU dlaT: disulfide oxidoreductase activity
myctu_dlat
Participant: Gene Product: dlaT
Gene Product:
dlaTUniProtKB:P9WIS7
Family:
MYCTU dlaT classification; exact product defines the activityPANTHER:PTHR43178:SF5
Representative Members: dlaTUniProtKB:P9WIS7

Function

disulfide oxidoreductase activityGO:0015036
Substrates: reduced dihydrolipoyl-DlaT oxidized AhpD
Products: oxidized lipoyl-DlaT reduced AhpD
Cofactors: covalently attached lipoate

Processes

cellular oxidant detoxificationGO:0098869

Covalently bound dihydrolipoyl groups on DlaT provide the reducing chemistry for AhpD. This is a lipoyl redox-carrier role, not the acetyl-transfer reaction or autonomous NADH oxidation.

PMID:11799204
Metabolic enzymes of mycobacteria linked to antioxidant defense by a thioredoxin-like protein.
The Mtb proteins define a lipoyl-mediated electron relay linking Lpd to AhpC through DlaT and AhpD.
The peroxiredoxin alkyl hydroperoxide reductase (AhpC) is linked to Lpd and SucB by an adaptor protein, AhpD.
PMID:16045627
Mycobacterium tuberculosis appears to lack alpha-ketoglutarate dehydrogenase and encodes pyruvate dehydrogenase in widely separated genes.
DlaT is experimentally the PDH E2 partner of Lpd, distinct from an oxoglutarate-dehydrogenase SucB assignment.
Finally, recombinant AceE, DlaT and Lpd, although encoded by genes that are widely separated on the chromosome, reconstituted PDH in vitro with Km values typical of bacterial PDH complexes.
MYCTU ahpD: disulfide oxidoreductase activity
myctu_ahpd
Participant: Gene Product: ahpD
Gene Product:
ahpDUniProtKB:P9WQB5
Family:
MYCTU ahpD classification; exact product defines the activityPANTHER:PTHR33930:SF7
Representative Members: ahpDUniProtKB:P9WQB5

Function

disulfide oxidoreductase activityGO:0015036
Substrates: reduced AhpD oxidized MYCTU AhpC
Products: oxidized AhpD reduced MYCTU AhpC

Processes

cellular oxidant detoxificationGO:0098869

AhpD transfers reducing equivalents to AhpC via a catalytic mixed disulfide; its weak direct peroxide side activity is not required for this relay.

PMID:15178486
Intermolecular interactions in the AhpC/AhpD antioxidant defense system of Mycobacterium tuberculosis.
Target AhpD directly reduces AhpC through a catalytic mixed disulfide.
A key step in the reduction of oxidized AhpC by reduced AhpD is formation of a disulfide cross-link between Cys61 of AhpC and Cys133 of AhpD.
PMID:11799204
Metabolic enzymes of mycobacteria linked to antioxidant defense by a thioredoxin-like protein.
The Mtb proteins define a lipoyl-mediated electron relay linking Lpd to AhpC through DlaT and AhpD.
The peroxiredoxin alkyl hydroperoxide reductase (AhpC) is linked to Lpd and SucB by an adaptor protein, AhpD.
MYCTU ahpC: peroxiredoxin activity
myctu_lipoyl_ahpc
Participant: Gene Product: ahpC
Gene Product:
ahpCUniProtKB:P9WQB7
Family:
MYCTU ahpC classification; exact product defines the activityPANTHER:PTHR10681:SF121
Representative Members: ahpCUniProtKB:P9WQB7

Function

peroxiredoxin activityGO:0051920
Substrates: reduced MYCTU AhpC hydrogen peroxide or accepted organic hydroperoxide
Products: oxidized MYCTU AhpC water or corresponding alcohol

Processes

cellular oxidant detoxificationGO:0098869

AhpC attacks peroxide downstream of the lipoyl relay. The four proteins contribute to the overall lipoyl/NADH-dependent system; AhpC is not asserted to contact NADH or DlaT directly.

PMID:11799204
Metabolic enzymes of mycobacteria linked to antioxidant defense by a thioredoxin-like protein.
The Mtb proteins define a lipoyl-mediated electron relay linking Lpd to AhpC through DlaT and AhpD.
The peroxiredoxin alkyl hydroperoxide reductase (AhpC) is linked to Lpd and SucB by an adaptor protein, AhpD.
PMID:15178486
Intermolecular interactions in the AhpC/AhpD antioxidant defense system of Mycobacterium tuberculosis.
Target AhpD directly reduces AhpC through a catalytic mixed disulfide.
A key step in the reduction of oxidized AhpC by reduced AhpD is formation of a disulfide cross-link between Cys61 of AhpC and Cys133 of AhpD.

Connections

myctu_lpd -> myctu_dlat Provides Input For
Lpd reduces the covalent lipoyl cofactor on DlaT.
PMID:11799204
Metabolic enzymes of mycobacteria linked to antioxidant defense by a thioredoxin-like protein.
The Mtb proteins define a lipoyl-mediated electron relay linking Lpd to AhpC through DlaT and AhpD.
The peroxiredoxin alkyl hydroperoxide reductase (AhpC) is linked to Lpd and SucB by an adaptor protein, AhpD.
PMID:16045627
Mycobacterium tuberculosis appears to lack alpha-ketoglutarate dehydrogenase and encodes pyruvate dehydrogenase in widely separated genes.
DlaT is experimentally the PDH E2 partner of Lpd, distinct from an oxoglutarate-dehydrogenase SucB assignment.
Finally, recombinant AceE, DlaT and Lpd, although encoded by genes that are widely separated on the chromosome, reconstituted PDH in vitro with Km values typical of bacterial PDH complexes.
myctu_dlat -> myctu_ahpd Provides Input For
Reduced lipoyl-DlaT supplies reducing equivalents to AhpD.
PMID:11799204
Metabolic enzymes of mycobacteria linked to antioxidant defense by a thioredoxin-like protein.
The Mtb proteins define a lipoyl-mediated electron relay linking Lpd to AhpC through DlaT and AhpD.
The peroxiredoxin alkyl hydroperoxide reductase (AhpC) is linked to Lpd and SucB by an adaptor protein, AhpD.
PMID:16045627
Mycobacterium tuberculosis appears to lack alpha-ketoglutarate dehydrogenase and encodes pyruvate dehydrogenase in widely separated genes.
DlaT is experimentally the PDH E2 partner of Lpd, distinct from an oxoglutarate-dehydrogenase SucB assignment.
Finally, recombinant AceE, DlaT and Lpd, although encoded by genes that are widely separated on the chromosome, reconstituted PDH in vitro with Km values typical of bacterial PDH complexes.
myctu_ahpd -> myctu_lipoyl_ahpc Provides Input For
AhpD reduces oxidized AhpC through mixed-disulfide exchange.
PMID:15178486
Intermolecular interactions in the AhpC/AhpD antioxidant defense system of Mycobacterium tuberculosis.
Target AhpD directly reduces AhpC through a catalytic mixed disulfide.
A key step in the reduction of oxidized AhpC by reduced AhpD is formation of a disulfide cross-link between Cys61 of AhpC and Cys133 of AhpD.