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.