{PDOC52045}
{PS52045; NEPROSIN_PEP_CD}
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* Neprosin prolyl endopeptidase (PEP) catalytic domain profile *
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Proteases are  a  class  of  enzymes that catalyze proteolysis, a process that
breaks down peptide bonds of protein into smaller polypeptides or amino acids.
Proteases are  involved in various biological processes, ranging from specific
proteolysis in the living organism to unspecific proteolysis of food proteins.
For instance,   proteases   play  important  roles  in  protein  localization,
modulation of protein-protein interactions, molecular signal transduction, and
generation of  cell  information.  Proteases have been reported to be secreted
into the  pitcher  fluids  of  Nepenthes, which is a genus in the Nepenthaceae
tropical carnivorous  pitcher  plant  family  with  over  170 species that are
studied to  understand  the  physiology and mechanisms of botanical carnivory.
Among them,  Neprosin  is  a  prolyl  endoprotease (PEP), which preferentially
cleaves C-terminal   to  proline  residues  under  highly  acidic  conditions.
Neprosin is produced and secreted as a zymogen, which is activated only in its
strongly acidic  natural  environment,  the  pitcher  plant  digestive  fluid.
Autolytic maturation yields the neprosin catalytic domain and the excised pro-
domain (PD).  Although  Neprosin-like  sequences  are  widely  found  in  (and
restricted to)  plants,  apart  from  their  involvement  in  the nutrition of
Nepenthes, their  function  in  plants  is poorly documented. New functions of
Neprosin-like proteins  in  plants during seed development have been suggested
[1,2,3,4].

The Neprosin  PEP  catalytic  domain  is an antiparallel beta-sandwich, with a
seven-stranded strongly-curled  front  sheet and an eight-stranded back sheet,
which provides  a  scaffold  for  the former (see <PDB:7ZU8>). Both sheets are
interconnected by  nine cross-over loops. There are two disulfide bonds (C1-C2
and C3-C34)  on either side of the sandwich. The Neprosin PEP catalytic domain
possess an  extended  active-site  cleft  traversing  the  concave face of the
sheet, which  is  oblique to the direction of the front-sheet beta-strands. It
features a  pair  of catalytic glutamates that are analogous to the aspartates
of the otherwise unrelated pepsin-type acidic endopeptidases [3].

The Neprosin PEP catalytic domain constitutes the peptidase family G3 of the G
clan.

The profile we developed covers the entire Neprosin PEP catalytic domain.

-Sequences known to belong to this class detected by the profile: ALL.
-Other sequence(s) detected in Swiss-Prot: NONE.
-Last update: June 2024 / First entry.

[ 1] Schraeder C.U., Lee L., Rey M., Sarpe V., Man P., Sharma S.,
     Zabrouskov V., Larsen B., Schriemer D.C.
     "Neprosin, a Selective Prolyl Endoprotease for Bottom-up Proteomics
     and Histone  Mapping."
     Mol. Cell. Proteomics. 16:1162-1171(2017).
     PubMed=28404794; DOI=10.1074/mcp.M116.066803
[ 2] Ting T.-Y., Baharin A., Ramzi A.B., Ng C.-L., Goh H.-H.
     "Neprosin belongs to a new family of glutamic peptidase based on in
     silico  evidence."
     Plant. Physiol. Biochem. 183:23-35(2022).
     PubMed=35537348; DOI=10.1016/j.plaphy.2022.04.027
[ 3] Del Amo-Maestro L., Mendes S.R., Rodriguez-Banqueri A.,
     Garzon-Flores L., Girbal M., Rodriguez-Lagunas M.J., Guevara T.,
     Franch A., Perez-Cano F.J., Eckhard U., Gomis-Rueth F.X.
     "Molecular and in vivo studies of a glutamate-class
     prolyl-endopeptidase for  coeliac disease therapy."
     Nat. Commun. 13:4446-4446(2022).
     PubMed=35915115; DOI=10.1038/s41467-022-32215-1
[ 4] Verges V., Bellenger L., Pichon O., Giglioli-Guivarc'h N.,
     Dutilleul C., Ducos E.
     "The Arabidopsis DUF239 gene family encodes Neprosin-like proteins
     that are widely  expressed in seed endosperm."
     Plant. Genome 16:E20290-E20290(2023).
     PubMed=36461675; DOI=10.1002/tpg2.20290

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