ldtA Resolved · high auto-curated

H37Rv Rv0116c · MTBC0 mtbc0_000127 · 251 aa · 140433–141188 (-) · RefSeq NP_214630.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)L,D-transpeptidase LdtA
MTBC0 PGAP re-annotationL%2CD-transpeptidase LdtMt1
Revised (this work)L%2CD-transpeptidase LdtMt1. 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 O53638 SwissProt · reviewed · Evidence at protein level
UniProt nameL,D-transpeptidase 1
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. Is thought to play a role in adaptation to the nonreplicative state of M.tuberculosis.

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category S Function unknown
eggNOG descriptionErfK YbiS YcfS YnhG family protein
Orthologous groupCOG1376
Gene Ontology (50) GO:0000270, GO:0003674, GO:0003824, GO:0004180, GO:0004185, GO:0005575, GO:0005576, GO:0006022, GO:0006023, GO:0006024, GO:0006508, GO:0006807 +38 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 1.403 · diversifying/relaxed
Polymorphic sites (≥ 0.1% of strains) 2 synonymous, 8 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 6.6e-2140–112 Bacterial Ig domain
YkuDPF03734.20 4.7e-24128–249 L,D-transpeptidase catalytic domain

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

Closest characterised functional partner: oxyS (oxidative stress response regulatory protein OxyS), high confidence from genomic context alone (score 751 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv0117 oxyS oxidative stress response regulatory protein OxyS 750 751 ctx neighborhood:748
Rv3015c hyp hypothetical protein 627 627 ctx cooccurence:627
Rv0017c rodA cell division protein RodA 524 503 database:500
Rv2413c hyp hypothetical protein 408 409 ctx cooccurence:407
Rv1140 integral membrane protein 407 200
Rv2911 dacB2 penicillin-binding protein DacB2 466 195
Rv3778c aminotransferase 461 84 textmining:436
Rv0115 hddA D-alpha-D-heptose-7-phosphate kinase HddA 440 50 textmining:435
Rv3682 ponA2 bifunctional penicillin-insensitive transglycosylase/penicillin-sensitive transpeptidase 414 50 textmining:409
Rv1863c integral membrane protein 525 49 textmining:522
Rv0050 ponA1 bifunctional penicillin-insensitive transglycosylase/penicillin-sensitive transpeptidase 660 47 textmining:658
Rv2769c PE27 PE family protein PE27 511 41 textmining:511
Rv2768c PPE43 PPE family protein PPE43 511 41 textmining:511

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 LdtA
  • MTBC0 PGAP product: L%2CD-transpeptidase LdtMt1
  • Pfam (hmmscan --cut_ga): Big_10 PF17964.8 (E=7e-21), YkuD PF03734.20 (E=5e-24)
  • (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_214630.1)
  • 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 O53638 (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 — 13 functional partner(s); context anchor oxyS
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_000127|Rv0116c|ldtA
MRRVVRYLSVVVAITLMLTAESVSIATAAVPPLQPIPGVASVSPANGAVVGVAHPVVVTFTTPVTDRRAVERSIRISTPHNTTGHFEWVASNVVRWVPHRYWPPHTRVSVGVQELTEGFETGDALIGVASISAHTFTVSRNGEVLRTMPASLGKPSRPTPIGSFHAMSKERTVVMDSRTIGIPLNSSDGYLLTAHYAVRVTWSGVYVHSAPWSVNSQGYANVSHGCINLSPDNAAWYFDAVTVGDPIEVVG