ldtB Resolved · high auto-curated

H37Rv Rv2518c · MTBC0 mtbc0_002681 · 408 aa · 2856999–2858225 (-) · RefSeq NP_217034.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)L,D-transpeptidase LdtB
MTBC0 PGAP re-annotationL%2CD-transpeptidase LdtMt2
Revised (this work)L%2CD-transpeptidase LdtMt2. Pfam: Big_10 (PF17964.8), YkuD (PF03734.20).

Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.

Curated reference (UniProt)

UniProt I6Y9J2 SwissProt · reviewed · Evidence at protein level
UniProt nameL,D-transpeptidase 2
EC (curated) EC 2.3.2.-
Curated functionGenerates 3->3 cross-links in peptidoglycan, catalyzing the cleavage of the mDap(3)-D-Ala(4) bond of a tetrapeptide donor stem and the formation of a bond between the carbonyl of mDap(3) of the donor stem and the side chain of mDap(3) of the acceptor stem. Is specific for donor substrates containing a stem tetrapeptide since it cannot use pentapeptide stems.

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category S Function unknown
Preferred namelppS
eggNOG descriptionErfK YbiS YcfS YnhG family protein
Orthologous groupCOG1376
Gene Ontology (38) GO:0000270, GO:0003674, GO:0003824, GO:0004180, GO:0004185, GO:0005575, GO:0005618, GO:0005623, GO:0006022, GO:0006508, GO:0006807, GO:0008150 +26 more

Orthology-based transfer (eggNOG 5.0.2, diamond). EC/KO/GO/CAZy are computed annotations, not manual curation; cross-check against the primary literature before treating a specific reaction as established.

Conservation & selection (intra-MTBC, 145 209 strains)

pN/pS 0.066 · strong purifying
Polymorphic sites (≥ 0.1% of strains) 5 synonymous, 1 missense, 0 nonsense, 0 frameshift

pN/pS from segregating SNPs (singletons removed) normalised by possible sites. Low pN/pS = purifying selection (a strong signal that a "hypothetical" is a real, constrained gene). A high pN/pS is ambiguous: relaxed constraint or positive selection (drug resistance, antigenic variation) inflate it; e.g. rpoB/katG/pncA score high here for resistance, not loss of function. A clonal disruption (one allele over a clade) suggests lineage pseudogenisation; a convergent one (many independent alleles) is typical of resistance loss-of-function.

Domains (Pfam, hmmscan --cut_ga)

PfamAccessioni-EvalueResiduesDescription
Big_10PF17964.8 2.8e-5971–232 Bacterial Ig domain
YkuDPF03734.20 4.5e-19256–377 L,D-transpeptidase catalytic domain

Functional interaction network (STRING v12, guilt-by-association)

Closest characterised functional partner: glfT2 (galactofuranosyl transferase GlfT), medium confidence from genomic context alone (score 522 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv3015c hyp hypothetical protein 611 611 ctx cooccurence:609
Rv3330 dacB1 penicillin-binding protein DacB 699 587 database:500
Rv2911 dacB2 penicillin-binding protein DacB2 655 580 database:500
Rv2413c hyp hypothetical protein 569 569 ctx cooccurence:569
Rv3808c glfT2 galactofuranosyl transferase GlfT 521 522 ctx cooccurence:520
Rv2673 aftC alpha-(1->3)-arabinofuranosyltransferase 514 515 ctx cooccurence:513
Rv3682 ponA2 bifunctional penicillin-insensitive transglycosylase/penicillin-sensitive transpeptidase 834 507 database:500 textmining:677
Rv0050 ponA1 bifunctional penicillin-insensitive transglycosylase/penicillin-sensitive transpeptidase 835 502 database:500 textmining:683
Rv0813c hyp hypothetical protein 495 495 ctx cooccurence:492
Rv1312 hyp hypothetical protein 493 493 ctx cooccurence:493
Rv3915 cwlM peptidoglycan hydrolase 507 476 ctx cooccurence:455
Rv0948c chorismate mutase 453 454 ctx cooccurence:452
Rv2239c hyp hypothetical protein 433 434 ctx cooccurence:430
Rv0225 hyp hypothetical protein 420 420 ctx cooccurence:420
Rv1022 lpqU lipoprotein LpqU 419 419 ctx cooccurence:418

STRING combines evidence channels (neighborhood, fusion, cooccurrence, coexpression, experimental, database, text-mining) into a 0–1000 score. The ctx badge marks edges carried by the genomic-context channels (conserved neighborhood, fusion, phylogenetic co-occurrence), which are independent of orthology and structure and the strongest signal for an unknown gene. The no text-mining column recomputes the score from data alone, so a link that does not depend on the literature is visible. Association is a function hypothesis, not proof: corroborate with the operon context and the primary literature before assigning a function.

Evidence

  • Legacy H37Rv annotation: L,D-transpeptidase LdtB
  • MTBC0 PGAP product: L%2CD-transpeptidase LdtMt2
  • Pfam (hmmscan --cut_ga): Big_10 PF17964.8 (E=3e-59), YkuD PF03734.20 (E=5e-19)
  • (auto-curated by rules from PGAP + Pfam + Foldseek; not hand-reviewed)

Sources

  • Ancestral sequence & coordinates: Harrison LB et al. (2024), An imputed ancestral reference genome for the MTBC, doi:10.1101/2023.09.07.556366
  • Product annotation: NCBI PGAP on MTBC0; legacy from H37Rv NC_000962.3 (RefSeq NP_217034.1)
  • Domains: Pfam-A via hmmscan --cut_ga — Big_10 (PF17964.8), YkuD (PF03734.20)
  • Sequence-level signal: ESM Atlas (EvolutionaryScale × BioHub) — exploratory
  • Controlled vocabulary: eggNOG-mapper 2.1.12 (Cantalapiedra et al. 2021, doi:10.1093/molbev/msab293), eggNOG 5.0 DB (Huerta-Cepas et al. 2019) — OG COG1376
  • Curated reference: UniProt I6Y9J2 (SwissProt, reviewed; Evidence at protein level)
  • Intra-MTBC selection: pN/pS and disruption from SPDI variants of 145 209 MTBC strains (this work, local collection vs H37Rv NC_000962.3)
  • Interaction network: STRING v12.0 (Szklarczyk et al. 2023, doi:10.1093/nar/gkac1000), taxon 83332, CC-BY 4.0 — 27 functional partner(s); context anchor glfT2
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_002681|Rv2518c|ldtB
MPKVGIAAQAGRTRVRRAWLTALMMTAVMIGAVACGSGRGPAPIKVIADKGTPFADLLVPKLTASVTDGAVGVTVDAPVSVTAADGVLAAVTMVNDNGRPVAGRLSPDGLRWSTTEQLGYNRRYTLNATALGLGGAATRQLTFQTSSPAHLTMPYVMPGDGEVVGVGEPVAIRFDENIADRGAAEKAIKITTNPPVEGAFYWLNNREVRWRPEHFWKPGTAVDVAVNTYGVDLGEGMFGEDNVQTHFTIGDEVIATADDNTKILTVRVNGEVVKSMPTSMGKDSTPTANGIYIVGSRYKHIIMDSSTYGVPVNSPNGYRTDVDWATQISYSGVFVHSAPWSVGAQGHTNTSHGCLNVSPSNAQWFYDHVKRGDIVEVVNTVGGTLPGIDGLGDWNIPWDQWRAGNAKA