2oq5
Crystal structure of DESC1, a new member of the type II transmembrane serine proteinases family
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OverviewOverview
DESC1 was identified using gene-expression analysis between squamous cell, carcinoma of the head and neck and normal tissue. It belongs to the type, II transmembrane multidomain serine proteinases (TTSPs), an expanding, family of serine proteinases, whose members are differentially expressed, in several tissues. The biological role of these proteins is currently, under investigation, although in some cases their participation in, specific functions has been reported. This is the case for, enteropeptidase, hepsin, matriptase and corin. Some members, including, DESC1, are associated with cell differentiation and have been described as, tumor markers. TTSPs belong to the type II transmembrane proteins that, display, in addition to a C-terminal trypsin-like serine proteinase, domain, a differing set of stem domains, a transmembrane segment and a, short N-terminal cytoplasmic region. Based on sequence analysis, the TTSP, family is subdivided into four subfamilies: hepsin/transmembrane, proteinase, serine (TMPRSS); matriptase; corin; and the human airway, trypsin (HAT)/HAT-like/DESC subfamily. Members of the hepsin and, matriptase subfamilies are known structurally and here we present the, crystal structure of DESC1 as a first member of the HAT/HAT-like/DESC, subfamily in complex with benzamidine. The proteinase domain of DESC1, exhibits a trypsin-like serine proteinase fold with a thrombin-like S1, pocket, a urokinase-type plasminogen activator-type S2 pocket, to accept, small residues, and an open hydrophobic S3/S4 cavity to accept large, hydrophobic residues. The deduced substrate specificity for DESC1 differs, markedly from that of other structurally known TTSPs. Based on surface, analysis, we propose a rigid domain association for the N-terminal SEA, domain with the back site of the proteinase domain.
About this StructureAbout this Structure
2OQ5 is a Single protein structure of sequence from Homo sapiens with BEN as ligand. Full crystallographic information is available from OCA.
ReferenceReference
Crystal structure of the catalytic domain of DESC1, a new member of the type II transmembrane serine proteinase family., Kyrieleis OJ, Huber R, Ong E, Oehler R, Hunter M, Madison EL, Jacob U, FEBS J. 2007 Mar 27;. PMID:17388811
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