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PROSITE documentation PDOC52029L,D-transpeptidase (L,D-TPase) catalytic domain profile
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PURL: https://purl.expasy.org/prosite/documentation/PDOC52029
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.
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PROSITE method (with tools and information) covered by this documentation:
| 1 | Authors | Magnet S. Arbeloa A. Mainardi J.-L. Hugonnet J.-E. Fourgeaud M. Dubost L. Marie A. Delfosse V. Mayer C. Rice L.B. Arthur M. |
| Title | Specificity of L,D-transpeptidases from gram-positive bacteria producing different peptidoglycan chemotypes. | |
| Source | J. Biol. Chem. 282:13151-13159(2007). | |
| PubMed ID | 17311917 | |
| DOI | 10.1074/jbc.M610911200 |
| 2 | Authors | Brammer Basta L.A. Ghosh A. Pan Y. Jakoncic J. Lloyd E.P. Townsend C.A. Lamichhane G. Bianchet M.A. |
| Title | Loss of a Functionally and Structurally Distinct ld-Transpeptidase, LdtMt5, Compromises Cell Wall Integrity in Mycobacterium tuberculosis. | |
| Source | J. Biol. Chem. 290:25670-25685(2015). | |
| PubMed ID | 26304120 | |
| DOI | 10.1074/jbc.M115.660753 |
| 3 | Authors | Kim 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. |
| Title | The Cell Shape-determining Csd6 Protein from Helicobacter pylori Constitutes a New Family of L,D-Carboxypeptidase. | |
| Source | J. Biol. Chem. 290:25103-25117(2015). | |
| PubMed ID | 26306031 | |
| DOI | 10.1074/jbc.M115.658781 |
| 4 | Authors | Caveney N.A. Caballero G. Voedts H. Niciforovic A. Worrall L.J. Vuckovic M. Fonvielle M. Hugonnet J.-E. Arthur M. Strynadka N.C.J. |
| Title | Structural insight into YcbB-mediated beta-lactam resistance in Escherichia coli. | |
| Source | Nat. Commun. 10:1849-1849(2019). | |
| PubMed ID | 31015395 | |
| DOI | 10.1038/s41467-019-09507-0 |
| 5 | Authors | Lin 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. |
| Title | Peptidoglycan binding by a pocket on the accessory NTF2-domain of Pgp2 directs helical cell shape of Campylobacter jejuni. | |
| Source | J. Biol. Chem. 296:100528-100528(2021). | |
| PubMed ID | 33711341 | |
| DOI | 10.1016/j.jbc.2021.100528 |
| 6 | Authors | Toth M. Stewart N.K. Smith C.A. Lee M. Vakulenko S.B. |
| Title | The l,d-Transpeptidase Ldt(Ab) from Acinetobacter baumannii Is Poorly Inhibited by Carbapenems and Has a Unique Structural Architecture. | |
| Source | ACS. Infect. Dis. 8:1948-1961(2022). | |
| PubMed ID | 35973205 | |
| DOI | 10.1021/acsinfecdis.2c00321 |
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