Bacterial DsbA/DsbB oxidative protein folding

A bacterial envelope mechanism in which a membrane DsbB-family relay regenerates oxidized DsbA-family proteins, which introduce disulfides into exported substrate proteins. Quinone-coupled recycling is directly established in selected systems; native acceptor identity and isolated kinetics remain unresolved for the Bacillus and Campylobacter comparisons. Catalytic domains act in the Gram-negative periplasm or outside the Bacillus cytoplasmic membrane. Initial disulfide insertion does not guarantee the native disulfide pattern. DsbC/DsbD repair and DsbA/VKOR oxidation are distinct mechanisms.

MODULE:bacterial_dsbab_oxidative_foldingCOMPLETECONCRETEBiological Processmodules/bacterial_dsbab_oxidative_folding.yaml
protein foldingGO:0006457
PMID:24576574
Disulfide bond formation in prokaryotes: history, diversity and design.
The DsbAB mechanism extends beyond Gammaproteobacteria to multiple bacterial lineages; bacterial scope does not imply presence in every bacterium or absence from archaea.
The cysteine counting approach and the identification of DsbA and DsbB homologues amongst prokaryotes suggests that protein disulfide bond formation and the DsbAB pathway are found in α, β, γ and ε-Proteopacteria, members of the phylum Deinococcus-Thermus, the Euryarchaeal family Halobacteriaceae and some Bacillales
PMID:34504665
Structural bioinformatic analysis of DsbA proteins and their pathogenicity associated substrates.
The E. coli single-DsbA model is not a universal architecture; paralog number and specialization vary across bacteria.
Genome-wide screening for DSB homologues has revealed that the classical model of bacterial oxidative folding from E. coli K-12 is not universally conserved across bacterial species
PMID:29463925
Disulfide bond formation in prokaryotes.
Actinobacterial and cyanobacterial DsbA systems can replace DsbB with VKOR; DsbA presence alone is insufficient to infer this DsbB-dependent module.
One variation found amongst Actinobacteria and Cyanobacteria is the replacement of DsbB by a homologue of human vitamin K epoxide reductase.
PMID:20367276
Mechanisms of oxidative protein folding in the bacterial cell envelope.
Joining cysteines and repairing misoxidized proteins are distinct tasks; the present module stops before the repair pathway.
Bacterial cells have evolved elaborate systems to promote the joining of two cysteines to form a disulfide bond and to repair misoxidized proteins.
PMID:40741763
Disulfide bonds are critical for stabilizing cell division, cell envelope biogenesis, and antibiotic resistance proteins in mycobacteria.
Mycobacterial oxidative protein folding is performed by DsbA and VKOR, validating an alternative outside this DsbB-dependent module.
Mycobacteria rely on two membrane enzymes, disulfide bond formation protein A (DsbA) and vitamin K epoxide reductase (VKOR), for introducing disulfide bonds into exported proteins.
PMID:38493438
Development of a sensor for disulfide bond formation in diverse bacteria.
The broad-host-range reporter is a tool for examining diverse disulfide-forming systems; it does not erase partner or strain specificity.
The use of the BHR plasmid-borne β-Gal dbs disulfide bond biosensor we describe here should enable this analysis in a greater diversity of bacteria.

The direction-neutral GO:0015035 definition includes oxidative protein-thiol chemistry despite its reductase label. Canonical DsbB quinone-coupled MF is more specific for its acceptor chemistry, but is not treated as an is_a refinement of every protein-disulfide term. Each family selector is representative-backed: no blanket catalytic grant is asserted for heterogeneous families and no ancestral node is invented. DsbB variants and substrate-oxidase variants are alternatives, not conjunctive requirements for every paralog. Production Boolean topology alone cannot establish partner compatibility; the audit retains exact pair witnesses with native, biochemical and inference evidence distinguished. Calcium changes BdbD redox properties without being established as a categorical capacity requirement. The 81116 DsbB current-record gap is bridged by explicitly archived identity, never by substituting another strain or inventing raw data. The scoped curation is complete; full-corpus validation, independent PR review, CI and actual merge remain required. Experimental and family-scope limits remain explicit.

13Nodes
3Parts
2Variant Sets
9Variants
10Annotons
2Connections

Derived QC

Recommended-field compliance

100.0% recommended fields populated

All recommended fields populated.

Module deep research

✗ none found

No MODULE:bacterial_dsbab_oxidative_folding 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

14 gene-function check(s) reflected in core functions · 0 conflict(s) · 6 evidence or coverage gap(s) (24 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
dsbb_oxidative_folding_component dsbB1 (PSEPK)
UniProtKB:P59345
Family Representative 		quinone-coupled DsbA oxidation
GO:0016672 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
dsbb_oxidative_folding_component dsbB2 (PSEPK)
UniProtKB:P59344
Family Representative 		quinone-coupled DsbA oxidation
GO:0016672 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
ecoli_dsbb_oxidative_folding_component dsbB (ECOLI)
UniProtKB:P0A6M2
Family Representative 		quinone-coupled DsbA oxidation
GO:0016672 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
pa14_dsbb1 dsbB1 (PSEAB)
UniProtKB:Q02TM7
Family Representative 		quinone-coupled DsbA oxidation
GO:0016672 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
pa14_dsbb2 dsbB2 (PSEAB)
UniProtKB:Q02EA7
Family Representative 		quinone-coupled DsbA oxidation
GO:0016672 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
bacillus_bdbc bdbC (BACSU)
UniProtKB:O32217
Family Representative 		protein thiol-disulfide oxidoreductase activity
GO:0015035 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
campylobacter_dsbb dsbB (CAMJ8)
UniProtKB:A8FLS4
Family Representative 		protein thiol-disulfide oxidoreductase activity
GO:0015035 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
dsba_disulfide_oxidoreductase dsbA (ECOLI)
UniProtKB:P0AEG4
Family Representative 		protein thiol-disulfide oxidoreductase activity
GO:0015035 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
dsba_disulfide_oxidoreductase dsbA (PSEPK)
UniProtKB:Q88RK2
Family Representative 		protein thiol-disulfide oxidoreductase activity
GO:0015035 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
dsba_disulfide_oxidoreductase dsbA (PSEAB)
UniProtKB:Q02DM0
Family Representative 		protein thiol-disulfide oxidoreductase activity
GO:0015035 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
bacillus_bdbd bdbD (BACSU)
UniProtKB:O32218
Family Representative 		protein thiol-disulfide oxidoreductase activity
GO:0015035 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
campylobacter_dsba B5Y32_04750 (CAMJU)
UniProtKB:A0A1J6PBD5
Family Representative 		protein thiol-disulfide oxidoreductase activity
GO:0015035 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
campylobacter_dsba F8Y55_09670 (CAMJU)
UniProtKB:A0A1J6UFJ6
Family Representative 		protein thiol-disulfide oxidoreductase activity
GO:0015035 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
pa14_dsba2_comparator PA14_59960 (PSEAB)
UniProtKB:A0A0H2ZG77
Family Representative 		protein thiol-disulfide oxidoreductase activity
GO:0015035 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
dsbb_oxidative_folding_component Pseudomonas-type DsbB proteins
PANTHER:PTHR36570:SF3
Family 		quinone-coupled DsbA oxidation
GO:0016672 		Family Supported
Family review supports GO:0016672 for PANTHER:PTHR36570:SF3. Purified E. coli and PA14 reconstitutions ground quinone-linked DsbB catalysis in the two DsbB subfamilies. SF1 DsbI is excluded from this family-scope assertion pending equivalent direct acceptor evidence; exclusion is an evidence boundary, not a demonstrated loss.
ecoli_dsbb_oxidative_folding_component Enterobacterial-type DsbB
PANTHER:PTHR36570:SF2
Family 		quinone-coupled DsbA oxidation
GO:0016672 		Family Supported
Family review supports GO:0016672 for PANTHER:PTHR36570:SF2. Purified E. coli and PA14 reconstitutions ground quinone-linked DsbB catalysis in the two DsbB subfamilies. SF1 DsbI is excluded from this family-scope assertion pending equivalent direct acceptor evidence; exclusion is an evidence boundary, not a demonstrated loss.
pa14_dsbb1 PA14 DsbB paralog
PANTHER:PTHR36570:SF2
Family 		quinone-coupled DsbA oxidation
GO:0016672 		Family Supported
Family review supports GO:0016672 for PANTHER:PTHR36570:SF2. Purified E. coli and PA14 reconstitutions ground quinone-linked DsbB catalysis in the two DsbB subfamilies. SF1 DsbI is excluded from this family-scope assertion pending equivalent direct acceptor evidence; exclusion is an evidence boundary, not a demonstrated loss.
pa14_dsbb2 PA14 DsbB paralog
PANTHER:PTHR36570:SF3
Family 		quinone-coupled DsbA oxidation
GO:0016672 		Family Supported
Family review supports GO:0016672 for PANTHER:PTHR36570:SF3. Purified E. coli and PA14 reconstitutions ground quinone-linked DsbB catalysis in the two DsbB subfamilies. SF1 DsbI is excluded from this family-scope assertion pending equivalent direct acceptor evidence; exclusion is an evidence boundary, not a demonstrated loss.
bacillus_bdbc BdbC-like membrane disulfide relay
PANTHER:PTHR43469:SF1
Family 		protein thiol-disulfide oxidoreductase activity
GO:0015035 		Family Function Unreviewed
Family review leaves GO:0015035 UNRESOLVED. BdbC partner architecture and native genetic evidence support protein-disulfide relay activity for the exemplar. The complete reaction has not been directly reconstituted here, and the available evidence does not establish this exact reaction for every member of the one broad subfamily. This does not negate the evidence-supported BdbC gene review.
campylobacter_dsbb 81116 DsbB with archived IPR003752/IPR023380/PF02600 classification
Family 		protein thiol-disulfide oxidoreductase activity
GO:0015035 		Family Id Missing
The family has no identifier linking it to a curated family review.
dsba_disulfide_oxidoreductase Canonical DsbA subfamily
PANTHER:PTHR35891:SF2
Family 		protein thiol-disulfide oxidoreductase activity
GO:0015035 		Family Function Unreviewed
Family review leaves GO:0015035 UNRESOLVED. The reversible protein thiol/disulfide reaction is established for active DsbA/DsbL representatives in SF2 and SF3, including both exact-sequence Campylobacter exemplars. However, the primary paper reports inactive truncated DsbA2 variants in other Campylobacter strains. Their exact current family and tree placement was not resolved here, so neither a whole-family grant nor a blanket exclusion of SF3 is justified. The positive SF2 PAINT node is assessed separately. No residue-loss branch or member exception is invented.
bacillus_bdbd Membrane-associated BdbD-like oxidoreductase
PANTHER:PTHR13887:SF14
Family 		protein thiol-disulfide oxidoreductase activity
GO:0015035 		Family Function Unreviewed
Family review leaves GO:0015035 UNRESOLVED. Direct BdbD peptide oxidation and PA14 DsbA2 biochemistry support these individual members. They do not establish protein-disulfide activity for every SF14 or SF56 descendant, much less the mixed family. The reversible GO reaction can represent oxidative direction where supported; no evolutionary loss or blanket absence is inferred.
campylobacter_dsba DsbL-related Campylobacter DsbA proteins
PANTHER:PTHR35891:SF3
Family 		protein thiol-disulfide oxidoreductase activity
GO:0015035 		Family Function Unreviewed
Family review leaves GO:0015035 UNRESOLVED. The reversible protein thiol/disulfide reaction is established for active DsbA/DsbL representatives in SF2 and SF3, including both exact-sequence Campylobacter exemplars. However, the primary paper reports inactive truncated DsbA2 variants in other Campylobacter strains. Their exact current family and tree placement was not resolved here, so neither a whole-family grant nor a blanket exclusion of SF3 is justified. The positive SF2 PAINT node is assessed separately. No residue-loss branch or member exception is invented.
pa14_dsba2_comparator PA14 DsbA2 thioredoxin-like oxidoreductase
PANTHER:PTHR13887:SF56
Family 		protein thiol-disulfide oxidoreductase activity
GO:0015035 		Family Function Unreviewed
Family review leaves GO:0015035 UNRESOLVED. Direct BdbD peptide oxidation and PA14 DsbA2 biochemistry support these individual members. They do not establish protein-disulfide activity for every SF14 or SF56 descendant, much less the mixed family. The reversible GO reaction can represent oxidative direction where supported; no evolutionary loss or blanket absence is inferred.

Gene-review completeness (14/14 grounded genes reviewed)

9 complete review(s) · 0 with deep research · 0 missing review · 14 reviewed but lacking deep research

Gene Review Complete Deep research
B5Y32_04750 A0A1J6PBD5 ✓ ✓ ✗
bdbC O32217 ✓ 5/7 ✗
bdbD O32218 ✓ 6/9 ✗
dsbA P0AEG4 ✓ 17/19 ✗
dsbA Q02DM0 ✓ ✓ ✗
dsbA Q88RK2 ✓ ✓ ✗
dsbB A8FLS4 ✓ ✓ ✗
dsbB P0A6M2 ✓ 14/15 ✗
dsbB1 P59345 ✓ ✓ ✗
dsbB1 Q02TM7 ✓ ✓ ✗
dsbB2 P59344 ✓ ✓ ✗
dsbB2 Q02EA7 ✓ ✓ ✗
F8Y55_09670 A0A1J6UFJ6 ✓ ✓ ✗
PA14_59960 A0A0H2ZG77 ✓ 1/2 ✗

Details

Context
BacteriaNCBITaxon:2

Comparative bacterial mechanism, not a claim of universal bacterial presence or absence from archaea. Representative lineages span Pseudomonadota, Bacillota and Campylobacterota; compatible pairs and evidence levels are explicit in the audit.

Bacterial DsbA/DsbB oxidative protein foldingBiological Processbacterial_dsbab_oxidative_folding
protein foldingGO:0006457
Context
BacteriaNCBITaxon:2

Comparative bacterial mechanism, not a claim of universal bacterial presence or absence from archaea. Representative lineages span Pseudomonadota, Bacillota and Campylobacterota; compatible pairs and evidence levels are explicit in the audit.

Connections

Regeneration supplies the oxidized catalytic state of a compatible DsbA-family protein. This is catalyst-state recycling, not direct transfer of an arbitrary small molecule between any two family hits.
PMID:12853466
Mechanism of the electron transfer catalyst DsbB from Escherichia coli.
E. coli DsbB directly catalyzes quinone-coupled oxidation of reduced DsbA.
The membrane protein DsbB from Escherichia coli is essential for disulfide bond formation and catalyses the oxidation of the periplasmic dithiol oxidase DsbA by ubiquinone.
PMID:24327342
Dissecting the machinery that introduces disulfide bonds in Pseudomonas aeruginosa.
PA14 DsbB1 and DsbB2 each reoxidize DsbA1; native deletion and biochemical evidence support alternative donors to the same recycling step.
We found that PaDsbA1, the primary donor of disulfide bonds to secreted proteins, is maintained oxidized in vivo by both PaDsbB1 and PaDsbB2.
PMID:11844773
Mutations in the thiol-disulfide oxidoreductases BdbC and BdbD can suppress cytochrome c deficiency of CcdA-defective Bacillus subtilis cells.
Bacillus BdbC and BdbD are an inferred cognate pair, with lower direct-reconstitution confidence than the E. coli and PA14 pairs.
This gene organization and the fact that BdbD and BdbC are apparent orthologs of E. coli DsbA and DsbB, respectively, indicate that BdbC and BdbD function as a pair.
PMID:34948248
Interplay between DsbA1, DsbA2 and C8J_1298 Periplasmic Oxidoreductases of Campylobacter jejuni and Their Impact on Bacterial Physiology and Pathogenesis.
Native loss of DsbB perturbs both DsbA paralogs, with reduced A1 and markedly diminished A2; the readouts are not identical.
in contrast to CjDsbA1, which in cells lacking its redox partner, was mainly present in a reduced form, the lack of CjDsbB led to almost undetectable levels of CjDsbA2.
Disulfide donation leaves reduced DsbA-family catalyst for partner-mediated recycling; not a guarantee of all-client folding or native disulfide pairing.
PMID:1429594
In vitro catalysis of oxidative folding of disulfide-bonded proteins by the Escherichia coli dsbA (ppfA) gene product.
Purified E. coli DsbA directly promotes disulfide formation in protein substrates.
Purified DsbA markedly stimulated disulfide bond formation of E. coli alkaline phosphatase, either in vitro synthesized or purified and denatured, as well as of reduced bovine ribonuclease A.
PMID:19535335
Crystal structure and biophysical properties of Bacillus subtilis BdbD. An oxidizing thiol:disulfide oxidoreductase containing a novel metal site.
Purified soluble BdbD transfers its own disulfide to a cysteine-containing substrate peptide.
These experiments clearly demonstrate that oxidized sBdbD is able to transfer its disulfide bond to the apo-cytochrome c550 active site mimic peptide.
PMID:24327342
Dissecting the machinery that introduces disulfide bonds in Pseudomonas aeruginosa.
PA14 DsbB1 and DsbB2 each reoxidize DsbA1; native deletion and biochemical evidence support alternative donors to the same recycling step.
We found that PaDsbA1, the primary donor of disulfide bonds to secreted proteins, is maintained oxidized in vivo by both PaDsbB1 and PaDsbB2.
Part: regeneration of oxidized DsbA-family partner
DsbB-dependent DsbA reoxidationReactiondsbb_dsbA_reoxidation

The membrane relay receives electrons from its compatible DsbA-family partner. Quinone-to-quinol chemistry is asserted specifically where supported; generic redox recycling remains explicit where acceptor chemistry is unresolved.

PMID:12853466
Mechanism of the electron transfer catalyst DsbB from Escherichia coli.
E. coli DsbB directly catalyzes quinone-coupled oxidation of reduced DsbA.
The membrane protein DsbB from Escherichia coli is essential for disulfide bond formation and catalyses the oxidation of the periplasmic dithiol oxidase DsbA by ubiquinone.
PMID:24327342
Dissecting the machinery that introduces disulfide bonds in Pseudomonas aeruginosa.
Reconstituted PA14 activity links DsbA1 oxidation to quinone reduction; interpretation retains the heterologous partially purified preparation limit.
In vitro reconstitution of the pathway confirms that both PaDsbB1 and PaDsbB2 shuttle electrons from PaDsbA1 to membrane-bound quinones.
PMID:11844773
Mutations in the thiol-disulfide oxidoreductases BdbC and BdbD can suppress cytochrome c deficiency of CcdA-defective Bacillus subtilis cells.
Bacillus BdbC and BdbD are an inferred cognate pair, with lower direct-reconstitution confidence than the E. coli and PA14 pairs.
This gene organization and the fact that BdbD and BdbC are apparent orthologs of E. coli DsbA and DsbB, respectively, indicate that BdbC and BdbD function as a pair.
PMID:34948248
Interplay between DsbA1, DsbA2 and C8J_1298 Periplasmic Oxidoreductases of Campylobacter jejuni and Their Impact on Bacterial Physiology and Pathogenesis.
Native loss of DsbB perturbs both DsbA paralogs, with reduced A1 and markedly diminished A2; the readouts are not identical.
in contrast to CjDsbA1, which in cells lacking its redox partner, was mainly present in a reduced form, the lack of CjDsbB led to almost undetectable levels of CjDsbA2.
Variant set: Alternative DsbB-family relays by experimentally grounded or qualified inferred protein implementation [Realizer] (One Or More)
KT2440 DsbB1 or DsbB2Reactiondsbb_oxidative_folding_component_implementation

Annotons

KT2440 DsbB1 or DsbB2
dsbb_oxidative_folding_component
Participant: Family: Pseudomonas-type DsbB proteins
Family:
Pseudomonas-type DsbB proteinsPANTHER:PTHR36570:SF3
Representative Members: dsbB1 (PSEPK)UniProtKB:P59345 dsbB2 (PSEPK)UniProtKB:P59344
Representative-backed role; family membership alone does not establish activity, donor compatibility or all-member inheritance.

Function

quinone-coupled DsbA oxidationGO:0016672
Substrates: reduced DsbA-family partner quinone
Products: oxidized DsbA-family partner quinol

Processes

protein foldingGO:0006457

Locations

plasma membraneGO:0005886

Curated ortholog inference for the two KT2440 paralogs; PA14 experiments do not constitute native KT2440 assays or prove their interchangeability under every condition.

file:PSEPK/dsbB1/dsbB1-uniprot.txt
Inferred to reoxidize reduced DsbA through a membrane quinone-linked electron-transfer relay; native KT2440 partner preferences and paralog redundancy are unresolved.
Belongs to the DsbB family.
file:PSEPK/dsbB2/dsbB2-uniprot.txt
Inferred to reoxidize reduced DsbA through a membrane quinone-linked electron-transfer relay; native KT2440 partner preferences and paralog redundancy are unresolved.
Belongs to the DsbB family.
E. coli DsbBReactionecoli_dsbb_oxidative_folding_component_implementation

Annotons

E. coli DsbB
ecoli_dsbb_oxidative_folding_component
Participant: Family: Enterobacterial-type DsbB
Family:
Enterobacterial-type DsbBPANTHER:PTHR36570:SF2
Representative Members: dsbB (ECOLI)UniProtKB:P0A6M2
Representative-backed role; family membership alone does not establish activity, donor compatibility or all-member inheritance.

Function

quinone-coupled DsbA oxidationGO:0016672
Substrates: reduced DsbA-family partner quinone
Products: oxidized DsbA-family partner quinol

Processes

protein foldingGO:0006457

Locations

plasma membraneGO:0005886

Direct quinone-coupled DsbA oxidation and native respiratory-chain dependence. Oxygen is not an asserted DsbB substrate.

PMID:12853466
Mechanism of the electron transfer catalyst DsbB from Escherichia coli.
E. coli DsbB directly catalyzes quinone-coupled oxidation of reduced DsbA.
The membrane protein DsbB from Escherichia coli is essential for disulfide bond formation and catalyses the oxidation of the periplasmic dithiol oxidase DsbA by ubiquinone.
PMID:9342327
Respiratory chain is required to maintain oxidized states of the DsbA-DsbB disulfide bond formation system in aerobically growing Escherichia coli cells.
Native respiratory-chain perturbations support electron transfer downstream of DsbB during maintenance of oxidized DsbA.
These results suggest that the respiratory electron transfer chain participates in the oxidation of DsbA, by acting primarily on DsbB.
PA14 dsbB1Reactionpa14_dsbb1_implementation

Annotons

PA14 dsbB1
pa14_dsbb1
Participant: Family: PA14 DsbB paralog
Family:
PA14 DsbB paralogPANTHER:PTHR36570:SF2
Representative Members: dsbB1 (PSEAB)UniProtKB:Q02TM7
Representative-backed role; family membership alone does not establish activity, donor compatibility or all-member inheritance.

Function

quinone-coupled DsbA oxidationGO:0016672
Substrates: reduced DsbA-family partner quinone
Products: oxidized DsbA-family partner quinol

Processes

protein foldingGO:0006457

Locations

plasma membraneGO:0005886

Native PA14 DsbA1 recycling is supported for either B1 or B2. Pre-enzyme controls, AMS confirmation and substrate-dependent initial velocities support inferred quinone-coupled catalysis. Heterologous partially purified preparations and exogenous decylubiquinone do not establish homogeneous isolated enzyme, a direct quinone-redox readout or a native quinone species.

PMID:24327342
Dissecting the machinery that introduces disulfide bonds in Pseudomonas aeruginosa.
PA14 DsbB1 and DsbB2 each reoxidize DsbA1; native deletion and biochemical evidence support alternative donors to the same recycling step.
We found that PaDsbA1, the primary donor of disulfide bonds to secreted proteins, is maintained oxidized in vivo by both PaDsbB1 and PaDsbB2.
PMID:24327342
Dissecting the machinery that introduces disulfide bonds in Pseudomonas aeruginosa.
Reconstituted PA14 activity links DsbA1 oxidation to quinone reduction; interpretation retains the heterologous partially purified preparation limit.
In vitro reconstitution of the pathway confirms that both PaDsbB1 and PaDsbB2 shuttle electrons from PaDsbA1 to membrane-bound quinones.
PA14 dsbB2Reactionpa14_dsbb2_implementation

Annotons

PA14 dsbB2
pa14_dsbb2
Participant: Family: PA14 DsbB paralog
Family:
PA14 DsbB paralogPANTHER:PTHR36570:SF3
Representative Members: dsbB2 (PSEAB)UniProtKB:Q02EA7
Representative-backed role; family membership alone does not establish activity, donor compatibility or all-member inheritance.

Function

quinone-coupled DsbA oxidationGO:0016672
Substrates: reduced DsbA-family partner quinone
Products: oxidized DsbA-family partner quinol

Processes

protein foldingGO:0006457

Locations

plasma membraneGO:0005886

Native PA14 DsbA1 recycling is supported for either B1 or B2. Pre-enzyme controls, AMS confirmation and substrate-dependent initial velocities support inferred quinone-coupled catalysis. Heterologous partially purified preparations and exogenous decylubiquinone do not establish homogeneous isolated enzyme, a direct quinone-redox readout or a native quinone species.

PMID:24327342
Dissecting the machinery that introduces disulfide bonds in Pseudomonas aeruginosa.
PA14 DsbB1 and DsbB2 each reoxidize DsbA1; native deletion and biochemical evidence support alternative donors to the same recycling step.
We found that PaDsbA1, the primary donor of disulfide bonds to secreted proteins, is maintained oxidized in vivo by both PaDsbB1 and PaDsbB2.
PMID:24327342
Dissecting the machinery that introduces disulfide bonds in Pseudomonas aeruginosa.
Reconstituted PA14 activity links DsbA1 oxidation to quinone reduction; interpretation retains the heterologous partially purified preparation limit.
In vitro reconstitution of the pathway confirms that both PaDsbB1 and PaDsbB2 shuttle electrons from PaDsbA1 to membrane-bound quinones.
Bacillus BdbCReactionbacillus_bdbc_implementation

Annotons

Bacillus BdbC
bacillus_bdbc
Participant: Family: BdbC-like membrane disulfide relay
Family:
BdbC-like membrane disulfide relayPANTHER:PTHR43469:SF1
Representative Members: bdbC (BACSU)UniProtKB:O32217
Representative-backed role; family membership alone does not establish activity, donor compatibility or all-member inheritance.

Function

protein thiol-disulfide oxidoreductase activityGO:0015035
Substrates: reduced DsbA-family partner
Products: oxidized DsbA-family partner

Processes

protein foldingGO:0006457

Locations

plasma membraneGO:0005886

Inferred BdbD-recycling relay from gene organization, cysteine/topology correspondence and genetics; purified BdbC quinone kinetics and native acceptor identity are unestablished.

PMID:11844773
Mutations in the thiol-disulfide oxidoreductases BdbC and BdbD can suppress cytochrome c deficiency of CcdA-defective Bacillus subtilis cells.
Bacillus BdbC and BdbD are an inferred cognate pair, with lower direct-reconstitution confidence than the E. coli and PA14 pairs.
This gene organization and the fact that BdbD and BdbC are apparent orthologs of E. coli DsbA and DsbB, respectively, indicate that BdbC and BdbD function as a pair.
PMID:11844773
Supports extracytoplasmic oxidative protein folding as the inferred BdbD-reoxidizing membrane relay. DsbB-family architecture and genetic substrate-folding evidence support the role, while the physiological quinone and coupled BdbC reaction remain unverified.
BdbC contains five cysteine residues, and four of them, Cys 34 , Cys 37 , Cys 95 , and Cys 101 , correspond in position to the four essential cysteines (Cys 41 , Cys 44 , Cys 104 , and Cys 130 ) in DsbB, which also has four transmembrane regions (Fig. 3 ) ( 2 ).
C. jejuni 81116 DsbBReactioncampylobacter_dsbb_implementation

Annotons

C. jejuni 81116 DsbB
campylobacter_dsbb
Participant: Family: 81116 DsbB with archived IPR003752/IPR023380/PF02600 classification
Family:
81116 DsbB with archived IPR003752/IPR023380/PF02600 classification Official UniSave v50 classification provides DsbB-domain/family support. No current PANTHER placement is established, so the family term is deliberately omitted.
Representative Members: dsbB (CAMJ8)UniProtKB:A8FLS4
Representative-backed role; family membership alone does not establish activity, donor compatibility or all-member inheritance.
file:genes/CAMJ8/dsbB/dsbB-source-analysis/archived-identity-and-assay-scope.md
Official archived identity and three-way full sequence match; current UniProt retrieval is empty.
Its 260-residue sequence matches ENA CP000814.1 translation ABV52411.1 and UniParc UPI00015D00EB exactly.

Function

protein thiol-disulfide oxidoreductase activityGO:0015035
Substrates: reduced DsbA-family partner
Products: oxidized DsbA-family partner

Processes

protein foldingGO:0006457

Locations

plasma membraneGO:0005886

Archived A8FLS4 is the exact 81116 sequence. Native A1 redox and A2 abundance effects support recycling; partially purified endpoint assays omitted a no-DsbB control. Native quinone and isolated coupled kinetics are unresolved.

PMID:34948248
Interplay between DsbA1, DsbA2 and C8J_1298 Periplasmic Oxidoreductases of Campylobacter jejuni and Their Impact on Bacterial Physiology and Pathogenesis.
Native loss of DsbB perturbs both DsbA paralogs, with reduced A1 and markedly diminished A2; the readouts are not identical.
in contrast to CjDsbA1, which in cells lacking its redox partner, was mainly present in a reduced form, the lack of CjDsbB led to almost undetectable levels of CjDsbA2.
PMID:34948248
Interplay between DsbA1, DsbA2 and C8J_1298 Periplasmic Oxidoreductases of Campylobacter jejuni and Their Impact on Bacterial Physiology and Pathogenesis.
The biochemical DsbB-dependent interpretation has a material control limitation; preserve this rather than claiming a fully controlled kinetic reconstitution.
we decided to exclude the experimental variant without the CjDsbB protein in our analysis
PMID:34948248
Reoxidizes the periplasmic DsbA1 and DsbA2 catalysts in the 81116 oxidative-folding system. Native redox-state evidence and tagged, partially purified-protein assays support this role; the native quinone and isolated coupled reaction kinetics remain undetermined.
The in vitro test indicated that CjDsbB oxidized both CjDsbA1 and CjDsbA2.
Part: disulfide introduction into exported substrate proteins
DsbA-family substrate oxidationReactiondsba_substrate_oxidation

Oxidized DsbA-family catalyst introduces a substrate disulfide and becomes reduced. Its own redox state is carried by cycle connections rather than treating the catalyst as its own substrate.

PMID:1429594
In vitro catalysis of oxidative folding of disulfide-bonded proteins by the Escherichia coli dsbA (ppfA) gene product.
Purified E. coli DsbA directly promotes disulfide formation in protein substrates.
Purified DsbA markedly stimulated disulfide bond formation of E. coli alkaline phosphatase, either in vitro synthesized or purified and denatured, as well as of reduced bovine ribonuclease A.
PMID:19535335
Crystal structure and biophysical properties of Bacillus subtilis BdbD. An oxidizing thiol:disulfide oxidoreductase containing a novel metal site.
Purified soluble BdbD transfers its own disulfide to a cysteine-containing substrate peptide.
These experiments clearly demonstrate that oxidized sBdbD is able to transfer its disulfide bond to the apo-cytochrome c550 active site mimic peptide.
PMID:34948248
Catalyzes protein disulfide introduction during oxidative folding, as demonstrated for the sequence-identical 81116 DsbA1 protein; native client preferences are incompletely resolved.
We found that both CjDsbAs recognized RNaseA as their substrate and exhibited oxidase activity such as that of EcDsbA
Variant set: Alternative substrate oxidases by experimentally grounded or qualified inferred protein implementation [Realizer] (One Or More)
Canonical bacterial DsbAReactiondsba_disulfide_oxidoreductase_implementation

Annotons

Canonical bacterial DsbA
dsba_disulfide_oxidoreductase
Participant: Family: Canonical DsbA subfamily
Family:
Canonical DsbA subfamilyPANTHER:PTHR35891:SF2
Representative Members: dsbA (ECOLI)UniProtKB:P0AEG4 dsbA (PSEPK)UniProtKB:Q88RK2 dsbA (PSEAB)UniProtKB:Q02DM0
Representative-backed role; family membership alone does not establish activity, donor compatibility or all-member inheritance.

Function

protein thiol-disulfide oxidoreductase activityGO:0015035
Substrates: exported substrate protein with reduced cysteine residues
Products: exported substrate protein containing a disulfide bond

Processes

protein foldingGO:0006457

Locations

outer membrane-bounded periplasmic spaceGO:0030288

Direct substrate oxidation in E. coli; native PA14 A1 recycling; KT2440 assignment is an explicit ortholog inference. These are cognate systems, not arbitrary cross-species mixing.

PMID:1429594
In vitro catalysis of oxidative folding of disulfide-bonded proteins by the Escherichia coli dsbA (ppfA) gene product.
Purified E. coli DsbA directly promotes disulfide formation in protein substrates.
Purified DsbA markedly stimulated disulfide bond formation of E. coli alkaline phosphatase, either in vitro synthesized or purified and denatured, as well as of reduced bovine ribonuclease A.
PMID:24327342
Dissecting the machinery that introduces disulfide bonds in Pseudomonas aeruginosa.
PA14 DsbB1 and DsbB2 each reoxidize DsbA1; native deletion and biochemical evidence support alternative donors to the same recycling step.
We found that PaDsbA1, the primary donor of disulfide bonds to secreted proteins, is maintained oxidized in vivo by both PaDsbB1 and PaDsbB2.
file:PSEPK/dsbA/dsbA-uniprot.txt
Inferred to introduce disulfide bonds into exported proteins during periplasmic oxidative folding.
CDD; cd03019; DsbA_DsbA; 1.
Bacillus BdbDReactionbacillus_bdbd_implementation

Annotons

Bacillus BdbD
bacillus_bdbd
Participant: Family: Membrane-associated BdbD-like oxidoreductase
Family:
Membrane-associated BdbD-like oxidoreductasePANTHER:PTHR13887:SF14
Representative Members: bdbD (BACSU)UniProtKB:O32218
Representative-backed role; family membership alone does not establish activity, donor compatibility or all-member inheritance.

Function

protein thiol-disulfide oxidoreductase activityGO:0015035
Substrates: exported substrate protein with reduced cysteine residues
Products: exported substrate protein containing a disulfide bond

Processes

protein foldingGO:0006457

Locations

plasma membraneGO:0005886

Catalytic domain acts outside the cytoplasmic membrane. Soluble-domain peptide oxidation is distinct from native membrane localization. A CXXCH peptide assay does not make this a positive cytochrome-maturation step.

PMID:19535335
Crystal structure and biophysical properties of Bacillus subtilis BdbD. An oxidizing thiol:disulfide oxidoreductase containing a novel metal site.
Bacillus BdbD acts on the external side of the cytoplasmic membrane, so a Gram-negative outer-membrane-bounded periplasm term cannot be imposed on the entire module.
BdbD is a thiol:disulfide oxidoreductase (TDOR) from Bacillus subtilis that functions to introduce disulfide bonds in substrate proteins/peptides on the outside of the cytoplasmic membrane
PMID:19535335
Crystal structure and biophysical properties of Bacillus subtilis BdbD. An oxidizing thiol:disulfide oxidoreductase containing a novel metal site.
Purified soluble BdbD transfers its own disulfide to a cysteine-containing substrate peptide.
These experiments clearly demonstrate that oxidized sBdbD is able to transfer its disulfide bond to the apo-cytochrome c550 active site mimic peptide.
C. jejuni DsbA1 or DsbA2Reactioncampylobacter_dsba_implementation

Annotons

C. jejuni DsbA1 or DsbA2
campylobacter_dsba
Participant: Family: DsbL-related Campylobacter DsbA proteins
Family:
DsbL-related Campylobacter DsbA proteinsPANTHER:PTHR35891:SF3
Representative Members: B5Y32_04750 (CAMJU)UniProtKB:A0A1J6PBD5 F8Y55_09670 (CAMJU)UniProtKB:A0A1J6UFJ6
Representative-backed role; family membership alone does not establish activity, donor compatibility or all-member inheritance.

Function

protein thiol-disulfide oxidoreductase activityGO:0015035
Substrates: exported substrate protein with reduced cysteine residues
Products: exported substrate protein containing a disulfide bond

Locations

outer membrane-bounded periplasmic spaceGO:0030288

Both oxidize RNase A in vitro, with different native client preferences and different dsbB-mutant readouts. Current species-level records match complete 81116 translations; their taxon labels are not rewritten as strain-specific records.

PMID:34948248
Interplay between DsbA1, DsbA2 and C8J_1298 Periplasmic Oxidoreductases of Campylobacter jejuni and Their Impact on Bacterial Physiology and Pathogenesis.
The 81116 system contains two DsbL-related monomeric oxidases with a shared DsbB, broadening the module beyond the canonical DsbA subfamily.
The oxidative part of this network consists of two monomeric DsbAs (DsbA1 and DsbA2) related to EcDsbL, which cooperate with one DsbB.
PMID:34948248
Catalyzes protein disulfide introduction during oxidative folding, as demonstrated for the sequence-identical 81116 DsbA1 protein; native client preferences are incompletely resolved.
We found that both CjDsbAs recognized RNaseA as their substrate and exhibited oxidase activity such as that of EcDsbA
file:genes/CAMJU/B5Y32_04750/B5Y32_04750-source-analysis/81116-sequence-bridge.md
Catalyzes protein disulfide introduction during oxidative folding, as demonstrated for the sequence-identical 81116 DsbA1 protein; native client preferences are incompletely resolved.
The two live UniProt sequences match their respective full translations and list the same UniParc identifiers.
Part: PA14 DsbA2 biochemical comparison with unresolved native role (optional)
Optional PA14 DsbA2 comparatorMolecular Functionpa14_dsba2_context
PMID:24327342
Dissecting the machinery that introduces disulfide bonds in Pseudomonas aeruginosa.
A2 remains a biochemically characterized alternative with unknown native expression conditions, not an established interchangeable native route.
PaDsbA2 was not detected, despite repeated attempts in different culture media, which suggests that this protein is expressed only under specific conditions that remain to be determined.

Annotons

PA14 DsbA2 biochemical comparator
pa14_dsba2_comparator
Participant: Family: PA14 DsbA2 thioredoxin-like oxidoreductase
Family:
PA14 DsbA2 thioredoxin-like oxidoreductasePANTHER:PTHR13887:SF56
Representative Members: PA14_59960 (PSEAB)UniProtKB:A0A0H2ZG77
Representative-backed role; family membership alone does not establish activity, donor compatibility or all-member inheritance.

Function

protein thiol-disulfide oxidoreductase activityGO:0015035

Insulin reduction and reoxidation by either PA14 DsbB establish biochemical redox competence. Native expression and productive client oxidation remain unresolved; this optional comparator does not substitute for DsbA1 in supported native pathway capacity.

PMID:24327342
Catalyzes protein-disulfide exchange demonstrated with recombinant DsbA2 and insulin; native substrate and physiological direction remain unresolved.
PaDsbA2 is able to catalyze insulin reduction, although less efficiently than EcDsbA and PaDsbA1.
PMID:24327342
Catalyzes protein-disulfide exchange demonstrated with recombinant DsbA2 and insulin; native substrate and physiological direction remain unresolved.
PaDsbA2 can be reoxidized by PaDsbB1 and PaDsbB2
PMID:24327342
Dissecting the machinery that introduces disulfide bonds in Pseudomonas aeruginosa.
A2 remains a biochemically characterized alternative with unknown native expression conditions, not an established interchangeable native route.
PaDsbA2 was not detected, despite repeated attempts in different culture media, which suggests that this protein is expressed only under specific conditions that remain to be determined.