2oq5
From Proteopedia
(New page: 200px<br /> <applet load="2oq5" size="450" color="white" frame="true" align="right" spinBox="true" caption="2oq5, resolution 1.61Å" /> '''Crystal structure o...) |
|||
| Line 1: | Line 1: | ||
| - | [[Image:2oq5.gif|left|200px]]<br /> | + | [[Image:2oq5.gif|left|200px]]<br /><applet load="2oq5" size="350" color="white" frame="true" align="right" spinBox="true" |
| - | <applet load="2oq5" size=" | + | |
caption="2oq5, resolution 1.61Å" /> | caption="2oq5, resolution 1.61Å" /> | ||
'''Crystal structure of DESC1, a new member of the type II transmembrane serine proteinases family'''<br /> | '''Crystal structure of DESC1, a new member of the type II transmembrane serine proteinases family'''<br /> | ||
==Overview== | ==Overview== | ||
| - | DESC1 was identified using gene-expression analysis between squamous cell | + | 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 Structure== | ==About this Structure== | ||
| - | 2OQ5 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with BEN as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http:// | + | 2OQ5 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=BEN:'>BEN</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2OQ5 OCA]. |
==Reference== | ==Reference== | ||
| - | 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 | + | 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:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=17388811 17388811] |
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
[[Category: Huber, R.]] | [[Category: Huber, R.]] | ||
| - | [[Category: Kyrieleis, O | + | [[Category: Kyrieleis, O J.P.]] |
| - | [[Category: Madison, E | + | [[Category: Madison, E L.]] |
[[Category: U., Jacob.]] | [[Category: U., Jacob.]] | ||
[[Category: BEN]] | [[Category: BEN]] | ||
| Line 23: | Line 22: | ||
[[Category: type ii trans-membrane serine proteinases]] | [[Category: type ii trans-membrane serine proteinases]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 18:21:17 2008'' |
Revision as of 16:21, 21 February 2008
|
Crystal structure of DESC1, a new member of the type II transmembrane serine proteinases family
Overview
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 Structure
2OQ5 is a Single protein structure of sequence from Homo sapiens with as ligand. Full crystallographic information is available from OCA.
Reference
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
Page seeded by OCA on Thu Feb 21 18:21:17 2008
