Family I37

Family

Summary Holotypes Alignment Tree Genomes Structure Literature

Summary for family I37

NameInhibitor family I37 (PCI family)
Family type peptidaseI37.001 - potato metallocarboxypeptidase inhibitor (Solanum tuberosum), MEROPS Accession MER0018230 (inhibitor unit: 1-39)
Content of familyPeptidase family I37 includes the potato carboxypeptidase inhibitor (PCI, I37.001), a metallocarboxypeptidase inhibitor.
History Identifier created: MEROPS 6.1 (10 January 2003)
An inhibitor of carboxypeptidase B (M14.003) was first isolated by Rancour & Ryan (1968).
Peptidases inhibitedPeptidases inhibited are metallocarboxypeptidases in family M14 (Marino-Buslje et al., 2000).
Mechanism of inhibitionThe four C-terminal residues of PCI bind into the active site pocket of carboxypeptidase A (M14.001). The C-terminal Gly is removed exposing Val38 as the new C-terminal residue. Gly remains bound to the S1" subsite with the carboxylate group of Val38 coordinating the Zn2+ of the active site until dissociation of the peptidase-inhibitor complex (Rees & Lipscomb, 1982). There is a secondary contact region involved in stabilising the peptidase-inhibitor complex. Mutation of Trp22, Phe23 and Trp28 to Ala results in 5-, 12- and 8-fold increases respectively in Ki (Arolas et al., 2004).
Molecular structurePCI is 39 residues in length. There are very few secondary structure elements present, with the inhibitor containing only one 310 helix turn and a very small beta-sheet (Rees & Lipscomb, 1982). Instead, the tertiary structure is maintained by three disulfide bonds which are in the unusual scaffold known as the "cysteine knot" or "T-knot" that is found in inhibitor family I7 and several growth factors including Epidermal growth factor and transforming growth factor alpha.
ClanIE
Distribution of family Bacteria -  
Archaea -  
Protozoa -  
Fungi -  
Plants details  
Animals -  
Viruses -  
Biological functionsPCI is one of a number of peptidase inhibitors that are synthesised by plants as a response to wounding by insects or other mechanical damage, following activation of the systemin signalling pathway (Ryan, 2000).
Pharmaceutical and biotech relevanceSitja-Arnau et al. (2005) demonstrated that PCI can prevent activation of the epidermal growth factor receptor signal transduction pathway through inhibition of epidermal growth factor and transforming growth factor-alpha, which suggests therapeutic potential in the treatment of carcinomas.
Statistics for family I37Sequences:14
Identifiers:1
Identifiers with PDB entries:1
Downloadable files Sequence library (FastA format)
Sequence alignment (FastA format)
Phylogenetic tree (Newick format)
Inhibitors and Homologues MEROPS ID Structure
potato metallocarboxypeptidase inhibitorI37.001Yes
family I37 unassigned peptidase inhibitor homologueshomologue-
family I37 unassigned peptidase inhibitorsunassigned-