{PDOC52035}
{PS52035; PEPTIDASE_M14}
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* Peptidase family M14 domain profile *
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Carboxypeptidases (CPs)  hydrolyse peptide bonds in target proteins to release
C-terminal amino  acids.  These  enzymes  have  been classified into different
families according  to sequence similarity, mechanism and function. One of the
largest groups,  carrying a single catalytic Zn(2+) in the active site, is the
M14 family.  This  is  divided into four subfamilies known as M14A, M14B, M14C
and M14D.  In  general, M14A and M14B carboxypeptidases either function within
the secretory  pathway  or  are  themselves  secreted. The members of the M14A
subfamily are  produced  as  pro-enzymes  that  are  activated  following  the
cleavage of  N-terminal  segments.  The  M14B subfamily are produced as active
enzymes with  a  transthyretin-like  domain  at the C-terminus. The M14C group
consists of    bacterial   enzymes   related   to   gamma-D-glutamyl-(L)-meso-
diaminopimelate peptidase I and process components of the bacterial cell wall.
Like their M14A relatives, they also carry an N-terminal extension. Members of
the M14D  subfamily   are referred to as cytosolic carboxypeptidases (CCPs) to
reflect their cellular location [1,2,3].

The M14  family  metallocarboxypeptidase  domain  displays an alpha/beta/alpha
sandwich structure  with  a  central  mixed  parallel-antiparallel  beta sheet
flanked on  both sides by several helices (see <PDB:2C1C>). The active site is
located at  the basis of a deep groove and consists of a distorted tetrahedral
Zn(2+) coordination site (a pair of histidines, a glutamate, and a coordinated
water molecule)  surrounded by catalytic residues that stabilize intermediates
during hydrolysis.  A Glu residue polarizes the nucleophilic water and donates
a hydrogen to the leaving amine [1,2,3].

The profile we developed covers the entire peptidase family M14 domain.

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

[ 1] Otero A., Rodriguez de la Vega M., Tanco S., Lorenzo J., Aviles F.X.,
     Reverter D.
     "The novel structure of a cytosolic M14 metallocarboxypeptidase (CCP)
     from  Pseudomonas aeruginosa: a model for mammalian CCPs."
     FASEB. J. 26:3754-3764(2012).
     PubMed=22645247; DOI=10.1096/fj.12-209601
[ 2] Rimsa V., Eadsforth T.C., Joosten R.P., Hunter W.N.
     "High-resolution structure of the M14-type cytosolic carboxypeptidase
     from  Burkholderia cenocepacia refined exploiting PDB_REDO
     strategies."
     Acta Crystallogr. D. Biol. Crystallogr. 70:279-289(2014).
     PubMed=24531462; DOI=10.1107/S1399004713026801
[ 3] Feld G.K., El-Etr S., Corzett M.H., Hunter M.S., Belhocine K.,
     Monack D.M., Frank M., Segelke B.W., Rasley A.
     "Structure and function of REP34 implicates carboxypeptidase activity
     in  Francisella tularensis host cell invasion."
     J. Biol. Chem. 289:30668-30679(2014).
     PubMed=25231992; DOI=10.1074/jbc.M114.599381

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