PROSITE documentation PDOC52029
L,D-transpeptidase (L,D-TPase) catalytic domain profile


Virtually all bacteria possess a peptidoglycan (PG) layer that encapsulates the cytoplasmic membrane and provides shape and rigidity to the cell. Considered as a vital bacterial "organelle", the PG is essential for cellular growth and viability. Mature PG comprises aminosugar strands with alternating N-acetylmuramic acid and N-acetylglucosamine units and peptide moieties that are cross-linked to one another. The final step of PG biosynthesis in bacteria involves cross-linking of peptide side chains. This step is catalyzed by L,D- and D,D-transpeptidases that generate 3->3 and 4->3 transpeptide linkages, respectively. Unlike D,D-transpeptidases that utilize a catalytic serine and pentapeptide substrates, L,D-transpeptidases require a catalytic cysteine residue and utilize tetrapeptide substrates. Members of the L,D-transpeptidase family can also display L,D-carboxypeptidase and L,D-endopeptidase activities [1,2,3,4,5,6].

The ~120-amino acid L,D-transpeptidase (L,D-TPase) catalytic domain consists of two curved, mixed β-sheets disposed in a clam-shell like manner with α-helices situated in the cleft between. The HX(15-18)[S/T]XGCh[N/R] motif (h represents a hydrophobic residue) is conserved among proteins containing an L,D-TPase catalytic domain and provides the two catalytic residues (His and Cys) which delineate the donor and acceptor regions of the active site [2,3,4,5,6].

Some proteins known to contain a L,D-TPase catalytic domain are listed below:

  • Mycobacterium L,D-transpeptidases 1-5.
  • Acinetobacter baumannii L,D-Transpeptidase AB.
  • Bacillus subtilis L,D-transpeptidase YkuD.
  • Escherichia coli L,D-transpeptidase YcbB.
  • Helicobacter pylori cell shape-determining L,D-carboxypeptidase Csd6.
  • Campylobacter jejuni LD-carboxypeptidase Pgp2.

The profile we developed covers the entire L,D-TPase domain.

Last update:

June 2023 / First entry.


Technical section

PROSITE method (with tools and information) covered by this documentation:

LD_TPASE, PS52029; L,D-transpeptidase (L,D-TPase) catalytic domain profile  (MATRIX)


1AuthorsMagnet S. Arbeloa A. Mainardi J.-L. Hugonnet J.-E. Fourgeaud M. Dubost L. Marie A. Delfosse V. Mayer C. Rice L.B. Arthur M.
TitleSpecificity of L,D-transpeptidases from gram-positive bacteria producing different peptidoglycan chemotypes.
SourceJ. Biol. Chem. 282:13151-13159(2007).
PubMed ID17311917

2AuthorsBrammer Basta L.A. Ghosh A. Pan Y. Jakoncic J. Lloyd E.P. Townsend C.A. Lamichhane G. Bianchet M.A.
TitleLoss of a Functionally and Structurally Distinct ld-Transpeptidase, LdtMt5, Compromises Cell Wall Integrity in Mycobacterium tuberculosis.
SourceJ. Biol. Chem. 290:25670-25685(2015).
PubMed ID26304120

3AuthorsKim H.S. Im H.N. An D.R. Yoon J.Y. Jang J.Y. Mobashery S. Hesek D. Lee M. Yoo J. Cui M. Choi S. Kim C. Lee N.K. Kim S.-J. Kim J.Y. Bang G. Han B.W. Lee B.I. Yoon H.J. Suh S.W.
TitleThe Cell Shape-determining Csd6 Protein from Helicobacter pylori Constitutes a New Family of L,D-Carboxypeptidase.
SourceJ. Biol. Chem. 290:25103-25117(2015).
PubMed ID26306031

4AuthorsCaveney N.A. Caballero G. Voedts H. Niciforovic A. Worrall L.J. Vuckovic M. Fonvielle M. Hugonnet J.-E. Arthur M. Strynadka N.C.J.
TitleStructural insight into YcbB-mediated beta-lactam resistance in Escherichia coli.
SourceNat. Commun. 10:1849-1849(2019).
PubMed ID31015395

5AuthorsLin C.S. Chan A.C.K. Vermeulen J. Brockerman J. Soni A.S. Tanner M.E. Gaynor E.C. McIntosh L.P. Simorre J.-P. Murphy M.E.P.
TitlePeptidoglycan binding by a pocket on the accessory NTF2-domain of Pgp2 directs helical cell shape of Campylobacter jejuni.
SourceJ. Biol. Chem. 296:100528-100528(2021).
PubMed ID33711341

6AuthorsToth M. Stewart N.K. Smith C.A. Lee M. Vakulenko S.B.
TitleThe l,d-Transpeptidase Ldt(Ab) from Acinetobacter baumannii Is Poorly Inhibited by Carbapenems and Has a Unique Structural Architecture.
SourceACS. Infect. Dis. 8:1948-1961(2022).
PubMed ID35973205

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