'''Crystal structure of DESC1, a new member of the type II transmembrane serine proteinases family'''
===Crystal structure of DESC1, a new member of the type II transmembrane serine proteinases family===
==Overview==
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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.
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==About this Structure==
==About this Structure==
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[[Category: Tumor marker]]
[[Category: Tumor marker]]
[[Category: Type ii trans-membrane serine proteinase]]
[[Category: Type ii trans-membrane serine proteinase]]
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Revision as of 05:41, 28 July 2008
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Crystal structure of DESC1, a new member of the type II transmembrane serine proteinases familyCrystal structure of DESC1, a new member of the type II transmembrane serine proteinases family
2OQ5 is a Single protein structure of sequence from Homo sapiens. 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 Apr;274(8):2148-60. Epub 2007 Mar 27. PMID:17388811
