PP_1451

Proposed New Ontology Terms

peptidoglycan-protein cross-link hydrolase activity

Definition: Catalysis of the hydrolysis of the amide bond that covalently links a protein, such as a Braun-lipoprotein-like outer-membrane lipoprotein, to a peptide stem of peptidoglycan.

Justification: GO:0018104 represents formation of a peptidoglycan-protein cross-link, but no molecular-function term identifies the reverse hydrolysis reaction. Generic carboxypeptidase activity does not specify the protein-peptidoglycan tether substrate.

Parent term: peptidoglycan endopeptidase activity

Existing Annotations Review

GO Term	Evidence	Action	Reason
GO:0000270 peptidoglycan metabolic process	IEA GO_REF:0000117	ACCEPT	Summary: PP_1451 is assigned to hydrolysis of a protein-peptidoglycan amide bond. Reason: Cleavage of the OprI tether directly remodels a peptidoglycan stem.
GO:0004180 carboxypeptidase activity	IEA GO_REF:0000117	KEEP AS NON CORE	Summary: E. coli LdtF/DpaA has a reported glycine-specific carboxypeptidase activity in addition to tether hydrolysis, and PAINT places this activity at the bacterial family node. Reason: PMID:33941679 directly reports terminal-glycine carboxypeptidase activity for LdtF, and PAINT independently places GO:0004180 at the PTHR36699 bacterial node from P0AA99. Retain this plausible inherited secondary activity, while treating tether hydrolysis as the predicted core role.
GO:0008360 regulation of cell shape	IEA GO_REF:0000104	MARK AS OVER ANNOTATED	Summary: Tether remodeling can affect envelope mechanics but does not establish direct regulation of cell shape. Reason: The supported direct role is hydrolysis of a peptidoglycan-protein cross-link.
GO:0016740 transferase activity	IEA GO_REF:0000002	REMOVE	Summary: The exact YafK/LdtPae3-related subfamily is assigned a hydrolytic rather than transfer reaction. Reason: A water-resolved acyl-enzyme cleaves the existing tether instead of transferring the peptidoglycan acyl group to an acceptor.
GO:0071555 cell wall organization	IEA GO_REF:0000104	ACCEPT	Summary: Releasing an outer-membrane lipoprotein from peptidoglycan remodels cell-envelope architecture. Reason: The reaction changes covalent connectivity between the outer membrane and sacculus.
GO:0009252 peptidoglycan biosynthetic process	IEA GO_REF:0000041	REMOVE	Summary: PP_1451 remodels an existing peptidoglycan-protein tether rather than synthesizing the glycan or stem. Reason: Hydrolysis of an existing tether is a remodeling reaction, not peptidoglycan biosynthesis.
GO:0030288 outer membrane-bounded periplasmic space	ISM file:PSEPK/PP_1451/PP_1451-uniprot.txt	NEW	Summary: PP_1451 is exported by a cleavable signal peptide to act on the peptidoglycan-lipoprotein tether. Reason: Its signal peptide and extracytoplasmic substrate support periplasmic localization.
GO:0004175 endopeptidase activity	IBD file:interpro/panther/PTHR36699/PTHR36699-paint.tsv	NEW	Summary: Broad family-level molecular function for the YafK/LdtF hydrolase subfamily. Reason: PAINT places GO:0004175 at a bacterial PTHR36699 ancestral node using experimentally characterized DpaA/P0AA99 as descendant evidence. The term is broader than the predicted tether chemistry but is the supported existing GO molecular function.
GO:0061785 peptidoglycan endopeptidase activity	ISS PMID:33941679 Cleavage of Braun's lipoprotein Lpp from the bacterial pepti...	NEW	Summary: The characterized LdtF/DpaA family activity is endopeptidase cleavage of a protein-peptidoglycan tether. Reason: GO:0061785 is the most specific available term for the demonstrated peptidoglycan-substrate endopeptidase activity; the proposed child would name the protein-tether specificity. Supporting Evidence: PMID:33941679 Here, using genetic and biochemical approaches, we show that LdtF (formerly yafK), a newly identified paralog of l,d-transpeptidases in E. coli, is a murein hydrolytic enzyme that catalyzes cleavage of Lpp from the PG sacculus.

Core Functions

Predicted periplasmic hydrolase that releases an OprI-like outer-membrane lipoprotein by cleaving its covalent amide bond to a peptidoglycan stem; GO:0061785 captures the established peptidoglycan-endopeptidase activity, while the proposed child would name the precise tether-hydrolysis chemistry.

Molecular Function:

peptidoglycan endopeptidase activity

Directly Involved In:

cell wall organization

Cellular Locations:

outer membrane-bounded periplasmic space

Supporting Evidence:

PMID:33941679
Here, using genetic and biochemical approaches, we show that LdtF (formerly yafK), a newly identified paralog of l,d-transpeptidases in E. coli, is a murein hydrolytic enzyme that catalyzes cleavage of Lpp from the PG sacculus.
PMID:33947763
We now show that LdtF hydrolyzes the Lpp-peptidoglycan linkage, detaching Lpp from peptidoglycan, and have renamed LdtF to peptidoglycan meso-diaminopimelic acid protein amidase A (DpaA).
PMID:37255442
The function of LdtPae3 was tentatively assigned to the release of OprI based on both the absence of detectable amide bond-forming activity (formation of 3→3 and tripeptide→ OprI bonds) and the close similarity between LdtPae3 and E. coli hydrolase YafK.

References

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Knowledge Gaps

What is not known — curated, literature-grounded statements of the open unknowns (the inverse of core functions).

Gap: PP_1451 tether-hydrolase activity and substrate specificity have not been tested directly in KT2440.

OPEN BIOLOGYCURATION

Significance: The assignment is supported by exact subfamily correspondence to tentatively assigned Pseudomonas LdtPae3 and experimentally characterized E. coli DpaA but remains inferred for KT2440.

Gap: The pathway-level report classified PP_1451 as an uncertain release candidate, while the PP_2320 gene-level report instead called PP_1451 a short LdtPae1-clade crosslinking candidate; both conclusions relied on short-range sequence comparisons that did not recover E. coli DpaA.

RESOLVED BIOLOGYCURATION

Significance: Exact PTHR36699:SF1 membership places PP_1451 with DpaA/P0AA99 and the PA14 LdtPae3 protein A0A0H2ZF55; this family and PAINT evidence is more discriminating than the report's k-mer and local-alignment metrics.

Gap: KT2440 may lack a dedicated 3-to-3 peptidoglycan-crosslinking L,D-transpeptidase if PP_2320 anchors OprI and PP_1451 releases the tether.

OPEN BIOLOGY

Significance: This is a testable genome-level consequence of assigning the organism's two YkuD-family proteins to tether writing and erasing rather than 3-to-3 crosslink formation.

Gene Description