Low-molecular-mass PBP peptidoglycan hydrolysis

A reusable bacterial module for two distinct hydrolytic reactions performed by low-molecular-mass penicillin-binding proteins during peptidoglycan maturation. D,D-carboxypeptidases trim terminal D-alanine from uncrosslinked pentapeptide stems, whereas D,D-endopeptidases cleave D-Ala-mDAP 4-3 crosslinks between stems. Individual enzymes may catalyze one or both reactions; neither reaction represents protein proteolysis or crosslink formation.

MODULE:low_molecular_mass_pbp_peptidoglycan_hydrolysisCOMPLETECONCRETEBiological Processmodules/low_molecular_mass_pbp_peptidoglycan_hydrolysis.yaml
peptidoglycan metabolic processGO:0000270
PMID:27716106
In vivo functional and molecular characterization of the Penicillin-Binding Protein 4 (DacB) of Pseudomonas aeruginosa.
Pseudomonas aeruginosa DacB/PBP4 catalyzes both reactions, with D,D-endopeptidase activity predominant.
LMM-PBP4 of Pseudomonas aeruginosa is a bifunctional enzyme presenting both D,D-carboxypeptidase and D,D-endopeptidase activities; the D,D-endopeptidase function is predominant.
PMID:2046551
Penicillin-binding protein 4 of Escherichia coli: molecular cloning of the dacB gene, controlled overexpression, and alterations in murein composition.
Escherichia coli PBP4 is a D,D-carboxypeptidase and D,D-endopeptidase and is not a transpeptidase.
PBP4 is not involved in transpeptidation but exclusively catalyses a DD-carboxypeptidase and DD-endopeptidase reaction.
PMID:25495032
Catalytic spectrum of the penicillin-binding protein 4 of Pseudomonas aeruginosa, a nexus for the induction of β-lactam antibiotic resistance.
Purified Pseudomonas aeruginosa PBP4 hydrolyses both pentapeptide stems and 4,3-crosslinks, but not 3,3-crosslinks.
PBP4 also has 4,3-endopeptidase activity but not 3,3-endopeptidase activity.
PMID:7925376
Penicillin-binding protein 7/8 of Escherichia coli is a DD-endopeptidase.
Escherichia coli PBP7 is a periplasmic D,D-endopeptidase acting on crosslinks in intact sacculi.
Murein meso-diaminopimelate-D-alanine DD-endopeptidase activity was demonstrated for both PBP7 and PBP8, which specifically hydrolyse the DD-diaminopimelate-alanine bonds in high-molecular-mass murein sacculi
PMID:8063800
Specific interaction of penicillin-binding proteins 3 and 7/8 with soluble lytic transglycosylase in Escherichia coli.
Escherichia coli PBP7/8 binds and stimulates the lytic transglycosylase Slt70, suggesting that PBP7 acts within a multi-enzyme hydrolase complex.
PBP7/8 was found not only to stabilize but also to stimulate the enzymatic activity of Slt70 by a protein-protein interaction.

The parts have equal order because stem trimming and crosslink hydrolysis are parallel remodeling reactions, not a compulsory linear sequence. DacB/PBP4 is intentionally represented in both parts because direct experiments on the Escherichia coli and Pseudomonas aeruginosa enzymes establish both activities. PbpG/PBP7 is represented only in the endopeptidase variant. GO:0009002 is not used as a proxy for crosslink hydrolysis because it names D,D-carboxypeptidase activity; GO:0061785 is used for the distinct peptidoglycan endopeptidase reaction. Scope: the module is species-neutral across Bacteria; exemplars are E. coli K-12 (the experimentally defining PBP4 and PBP7), P. aeruginosa PAO1 (direct PBP4 enzymology) and P. putida KT2440 (orthologs grounded by PANTHER subfamily). Family groundings: PANTHER:PTHR30023:SF0 (the only subfamily of the S13 PBP4 family) and PANTHER:PTHR21581:SF26 (the PBP7 endopeptidase subfamily of the heterogeneous S11 family); both families have reviews under interpro/panther/. The PTHR30023 review leaves GO:0061785 UNRESOLVED at family level, because endopeptidase activity is shown only for the Gram-negative PBP4 enzymes and the family also contains Dictyostelium PscA, which has no peptidoglycan substrate; the resulting FAMILY_FUNCTION_UNREVIEWED warning on the DacB endopeptidase annoton is expected and is satisfied at member level by the three reviewed PBP4 exemplars. For the same reason (PscA's substrate is unknown and no PANTHER subfamily isolates the bacterial clade) the review leaves GO:0009002 UNRESOLVED at family level, giving the matching expected warning on the DacB carboxypeptidase annoton; the GO:0009002 activity of the three exemplars rests on their own gene reviews. Stem trimming is modelled as a variant set (selection ONE_OR_MORE) so that further carboxypeptidase families can be added as variants. The S11 DacA/PBP5-type D,D-carboxypeptidases are the principal stem trimmers in E. coli but are not yet modelled here; the KT2440 dacA review is being curated with the peptidoglycan polymerization module and E. coli dacA has no review yet. No module deep-research report was generated (no provider credentials available). Follow-up: the gene reviews record the InterPro2GO mapping of IPR000667, IPR001967 and IPR018044 to GO:0006508 proteolysis as source defects; a matching removal row in projects/INTERPRO/interpro2go.sssom.yaml still needs the README's sole-source and rule-cover checks and is left for a separate change.

6Nodes
2Parts
2Variant Sets
3Variants
3Annotons
0Connections

Derived QC

Recommended-field compliance

100.0% recommended fields populated

All recommended fields populated.

Module deep research

✗ none found

No MODULE:low_molecular_mass_pbp_peptidoglycan_hydrolysis 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

8 gene-function check(s) reflected in core functions · 0 conflict(s) · 2 evidence or coverage gap(s) (11 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
dacb_dd_carboxypeptidase dacB / PBP4 (Escherichia coli K-12)
UniProtKB:P24228
Family Representative 		serine-type D,D-carboxypeptidase activity
GO:0009002 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
dacb_dd_carboxypeptidase dacB / PBP4 (Pseudomonas aeruginosa PAO1)
UniProtKB:Q9HZG1
Family Representative 		serine-type D,D-carboxypeptidase activity
GO:0009002 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
dacb_dd_carboxypeptidase dacB / PBP4 (Pseudomonas putida KT2440)
UniProtKB:Q88L37
Family Representative 		serine-type D,D-carboxypeptidase activity
GO:0009002 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
dacb_dd_endopeptidase dacB / PBP4 (Escherichia coli K-12)
UniProtKB:P24228
Family Representative 		peptidoglycan D,D-endopeptidase activity
GO:0061785 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
dacb_dd_endopeptidase dacB / PBP4 (Pseudomonas aeruginosa PAO1)
UniProtKB:Q9HZG1
Family Representative 		peptidoglycan D,D-endopeptidase activity
GO:0061785 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
dacb_dd_endopeptidase dacB / PBP4 (Pseudomonas putida KT2440)
UniProtKB:Q88L37
Family Representative 		peptidoglycan D,D-endopeptidase activity
GO:0061785 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
pbpg_dd_endopeptidase pbpG / PBP7 (Escherichia coli K-12)
UniProtKB:P0AFI5
Family Representative 		peptidoglycan D,D-endopeptidase activity
GO:0061785 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
pbpg_dd_endopeptidase pbpG / PBP7 (Pseudomonas putida KT2440)
UniProtKB:Q88GD0
Family Representative 		peptidoglycan D,D-endopeptidase activity
GO:0061785 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
dacb_dd_carboxypeptidase DacB/PBP4 peptidase S13 family
PANTHER:PTHR30023:SF0
Family 		serine-type D,D-carboxypeptidase activity
GO:0009002 		Family Function Unreviewed
Family review leaves GO:0009002 UNRESOLVED. D-Ala-D-Ala carboxypeptidase activity on peptidoglycan stems is a bacterial claim. It is shown experimentally for E. coli PBP4 and P. aeruginosa PBP4, and the catalytic SXXK, SXN and KTG motifs are conserved in the bacterial members, but the substrate of Dictyostelium PscA is unknown (its organism has no peptidoglycan, and the carboxypeptidase activity reported for it names no substrate). PANTHER has a single subfamily (SF0) that contains PscA, so no subfamily isolates the bacterial clade and the term cannot be scoped FAMILY_WIDE or SUBFAMILY_ONLY. Resolving it needs the substrate specificity of PscA, or a clade split that separates the eukaryotic branch.
dacb_dd_endopeptidase DacB/PBP4 peptidase S13 family
PANTHER:PTHR30023:SF0
Family 		peptidoglycan D,D-endopeptidase activity
GO:0061785 		Family Function Unreviewed
Family review leaves GO:0061785 UNRESOLVED. D,D-endopeptidase (4,3-crosslink) activity is experimentally established for the Gram-negative PBP4 enzymes of E. coli and P. aeruginosa, and the KT2440 ortholog inherits it by close orthology. It cannot be family-wide because Dictyostelium PscA has no peptidoglycan substrate, and endopeptidase assays are missing for the Bacillus and actinobacterial members; PANTHER has no subfamily that isolates the Gram-negative PBP4 clade. Resolving the scope needs endopeptidase assays on B. subtilis DacC and mycobacterial DacB, or a finer clade split (NCBIfam TIGR00666 covers PscA as well and does not separate it).
pbpg_dd_endopeptidase PbpG/PBP7 peptidase S11 family
PANTHER:PTHR21581:SF26
Family 		peptidoglycan D,D-endopeptidase activity
GO:0061785 		Family Supported
Family review supports GO:0061785 for PANTHER:PTHR21581:SF26. D,D-endopeptidase cleavage of 4-3 crosslinks is demonstrated for E. coli PBP7, the type member of SF26; the other subfamilies are carboxypeptidases or, for TRAPPC12, not peptidases.

Gene-review completeness (5/5 grounded genes reviewed)

5 complete review(s) · 2 with deep research · 0 missing review · 3 reviewed but lacking deep research

Gene Review Complete Deep research
dacB P24228 ✓ ✓ ✗
dacB Q88L37 ✓ ✓ ✓
PA3047 Q9HZG1 ✓ ✓ ✗
pbpG P0AFI5 ✓ ✓ ✗
pbpG Q88GD0 ✓ ✓ ✓

Details

Context
bacteriaNCBITaxon:2
Low-molecular-mass PBP peptidoglycan hydrolysisBiological Processlow_molecular_mass_pbp_peptidoglycan_hydrolysis
peptidoglycan metabolic processGO:0000270
Context
bacteriaNCBITaxon:2
Part 1: pentapeptide stem trimming
Peptidoglycan pentapeptide stem trimmingReactionpentapeptide_stem_trimming
Variant set: Low-molecular-mass PBP D,D-carboxypeptidases by enzyme family (One Or More)
Bifunctional DacB/PBP4 variantReactiondacb_carboxypeptidase_variant

Annotons

DacB/PBP4 D,D-carboxypeptidase activity
dacb_dd_carboxypeptidase
Participant: Family: DacB/PBP4 peptidase S13 family
Family:
DacB/PBP4 peptidase S13 familyPANTHER:PTHR30023:SF0
Representative Members: dacB / PBP4 (Escherichia coli K-12)UniProtKB:P24228 dacB / PBP4 (Pseudomonas aeruginosa PAO1)UniProtKB:Q9HZG1 dacB / PBP4 (Pseudomonas putida KT2440)UniProtKB:Q88L37

Function

serine-type D,D-carboxypeptidase activityGO:0009002
Substrates: peptidoglycan pentapeptide stem water
Products: peptidoglycan tetrapeptide stem D-alanine

Processes

peptidoglycan metabolic processGO:0000270

Removes terminal D-alanine from an uncrosslinked pentapeptide stem.

Part 1: 4-3 peptidoglycan crosslink hydrolysis