{PDOC52029}
{PS52029; LD_TPASE}
{BEGIN}
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* L,D-transpeptidase (L,D-TPase) catalytic domain profile *
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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  beta-sheets  disposed in a clam-shell like manner with
alpha-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.

-Sequences known to belong to this class detected by the profile: ALL.
-Other sequence(s) detected in Swiss-Prot: NONE.
-Last update: June 2023 / First entry.

[ 1] 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.
     "Specificity of L,D-transpeptidases from gram-positive bacteria
     producing  different peptidoglycan chemotypes."
     J. Biol. Chem. 282:13151-13159(2007).
     PubMed=17311917; DOI=10.1074/jbc.M610911200
[ 2] Brammer Basta L.A., Ghosh A., Pan Y., Jakoncic J., Lloyd E.P.,
     Townsend C.A., Lamichhane G., Bianchet M.A.
     "Loss of a Functionally and Structurally Distinct ld-Transpeptidase,
     LdtMt5,  Compromises Cell Wall Integrity in Mycobacterium
     tuberculosis."
     J. Biol. Chem. 290:25670-25685(2015).
     PubMed=26304120; DOI=10.1074/jbc.M115.660753
[ 3] 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.
     "The Cell Shape-determining Csd6 Protein from Helicobacter pylori
     Constitutes a  New Family of L,D-Carboxypeptidase."
     J. Biol. Chem. 290:25103-25117(2015).
     PubMed=26306031; DOI=10.1074/jbc.M115.658781
[ 4] 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.
     "Structural insight into YcbB-mediated beta-lactam resistance in
     Escherichia coli."
     Nat. Commun. 10:1849-1849(2019).
     PubMed=31015395; DOI=10.1038/s41467-019-09507-0
[ 5] 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.
     "Peptidoglycan binding by a pocket on the accessory NTF2-domain of
     Pgp2 directs  helical cell shape of Campylobacter jejuni."
     J. Biol. Chem. 296:100528-100528(2021).
     PubMed=33711341; DOI=10.1016/j.jbc.2021.100528
[ 6] Toth M., Stewart N.K., Smith C.A., Lee M., Vakulenko S.B.
     "The l,d-Transpeptidase Ldt(Ab) from Acinetobacter baumannii Is Poorly
     Inhibited  by Carbapenems and Has a Unique Structural Architecture."
     ACS. Infect. Dis. 8:1948-1961(2022).
     PubMed=35973205; DOI=10.1021/acsinfecdis.2c00321

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