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PDBsum entry 2oq5
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References listed in PDB file
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Key reference
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Title
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Crystal structure of the catalytic domain of desc1, A new member of the type ii transmembrane serine proteinase family.
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Authors
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O.J.Kyrieleis,
R.Huber,
E.Ong,
R.Oehler,
M.Hunter,
E.L.Madison,
U.Jacob.
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Ref.
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Febs J, 2007,
274,
2148-2160.
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PubMed id
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Abstract
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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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