2bo9

From Proteopedia

Revision as of 08:26, 3 February 2008

HUMAN CARBOXYPEPTIDASE A4 IN COMPLEX WITH HUMAN LATEXIN.

Overview

The only endogenous protein inhibitor known for metallocarboxypeptidases, (MCPs) is latexin, a 25-kDa protein discovered in the rat brain. Latexin, alias endogenous carboxypeptidase inhibitor, inhibits human CPA4 (hCPA4), whose expression is induced in prostate cancer cells after treatment with, histone deacetylase inhibitors. hCPA4 is a member of the A/B subfamily of, MCPs and displays the characteristic alpha/beta-hydrolase fold. Human, latexin consists of two topologically equivalent subdomains, reminiscent, of cystatins, consisting of an alpha-helix enveloped by a curved, beta-sheet. These subdomains are packed against each other through the, helices and linked by a connecting segment encompassing a third, alpha-helix. The enzyme is bound at the interface of these subdomains. The, complex occludes a large contact surface but makes rather few contacts, despite a nanomolar inhibition constant. This low specificity explains the, flexibility of latexin in inhibiting all vertebrate A/B MCPs tested, even, across species barriers. In contrast, modeling studies reveal why the N/E, subfamily of MCPs and invertebrate A/B MCPs are not inhibited. Major, differences in the loop segments shaping the border of the funnel-like, access to the protease active site impede complex formation with latexin., Several sequences ascribable to diverse tissues and organs have been, identified in vertebrate genomes as being highly similar to latexin. They, are proposed to constitute the latexin family of potential inhibitors., Because they are ubiquitous, latexins could represent for vertebrate A/B, MCPs the counterparts of tissue inhibitors of metalloproteases for matrix, metalloproteinases.

About this Structure

2BO9 is a Protein complex structure of sequences from Homo sapiens with , , , and as ligands. This structure superseeds the now removed PDB entry 2BK7. Known structural/functional Site: . Full crystallographic information is available from OCA.

Reference

Structure of human carboxypeptidase A4 with its endogenous protein inhibitor, latexin., Pallares I, Bonet R, Garcia-Castellanos R, Ventura S, Aviles FX, Vendrell J, Gomis-Ruth FX, Proc Natl Acad Sci U S A. 2005 Mar 15;102(11):3978-83. Epub 2005 Feb 28. PMID:15738388

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