1eaw
From Proteopedia
(New page: 200px<br /> <applet load="1eaw" size="450" color="white" frame="true" align="right" spinBox="true" caption="1eaw, resolution 2.93Å" /> '''CRYSTAL STRUCTURE O...) |
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| - | [[Image:1eaw.gif|left|200px]]<br /> | + | [[Image:1eaw.gif|left|200px]]<br /><applet load="1eaw" size="350" color="white" frame="true" align="right" spinBox="true" |
| - | <applet load="1eaw" size=" | + | |
caption="1eaw, resolution 2.93Å" /> | caption="1eaw, resolution 2.93Å" /> | ||
'''CRYSTAL STRUCTURE OF THE MTSP1 (MATRIPTASE)-BPTI (APROTININ) COMPLEX'''<br /> | '''CRYSTAL STRUCTURE OF THE MTSP1 (MATRIPTASE)-BPTI (APROTININ) COMPLEX'''<br /> | ||
==Overview== | ==Overview== | ||
| - | The type II transmembrane multidomain serine proteinase MT-SP1/matriptase | + | The type II transmembrane multidomain serine proteinase MT-SP1/matriptase is highly expressed in many human cancer-derived cell lines and has been implicated in extracellular matrix re-modeling, tumor growth, and metastasis. We have expressed the catalytic domain of MT-SP1 and solved the crystal structures of complexes with benzamidine at 1.3 A and bovine pancreatic trypsin inhibitor at 2.9 A. MT-SP1 exhibits a trypsin-like serine proteinase fold, featuring a unique nine-residue 60-insertion loop that influences interactions with protein substrates. The structure discloses a trypsin-like S1 pocket, a small hydrophobic S2 subsite, and an open negatively charged S4 cavity that favors the binding of basic P3/P4 residues. A complementary charge pattern on the surface opposite the active site cleft suggests a distinct docking of the preceding low density lipoprotein receptor class A domain. The benzamidine crystals possess a freely accessible active site and are hence well suited for soaking small molecules, facilitating the improvement of inhibitors. The crystal structure of the MT-SP1 complex with bovine pancreatic trypsin inhibitor serves as a model for hepatocyte growth factor activator inhibitor 1, the physiological inhibitor of MT-SP1, and suggests determinants for the substrate specificity. |
==Disease== | ==Disease== | ||
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==About this Structure== | ==About this Structure== | ||
| - | 1EAW is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Bos_taurus Bos taurus] and [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http:// | + | 1EAW is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Bos_taurus Bos taurus] and [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1EAW OCA]. |
==Reference== | ==Reference== | ||
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[[Category: serine proteinase]] | [[Category: serine proteinase]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 12:25:48 2008'' |
Revision as of 10:25, 21 February 2008
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CRYSTAL STRUCTURE OF THE MTSP1 (MATRIPTASE)-BPTI (APROTININ) COMPLEX
Contents |
Overview
The type II transmembrane multidomain serine proteinase MT-SP1/matriptase is highly expressed in many human cancer-derived cell lines and has been implicated in extracellular matrix re-modeling, tumor growth, and metastasis. We have expressed the catalytic domain of MT-SP1 and solved the crystal structures of complexes with benzamidine at 1.3 A and bovine pancreatic trypsin inhibitor at 2.9 A. MT-SP1 exhibits a trypsin-like serine proteinase fold, featuring a unique nine-residue 60-insertion loop that influences interactions with protein substrates. The structure discloses a trypsin-like S1 pocket, a small hydrophobic S2 subsite, and an open negatively charged S4 cavity that favors the binding of basic P3/P4 residues. A complementary charge pattern on the surface opposite the active site cleft suggests a distinct docking of the preceding low density lipoprotein receptor class A domain. The benzamidine crystals possess a freely accessible active site and are hence well suited for soaking small molecules, facilitating the improvement of inhibitors. The crystal structure of the MT-SP1 complex with bovine pancreatic trypsin inhibitor serves as a model for hepatocyte growth factor activator inhibitor 1, the physiological inhibitor of MT-SP1, and suggests determinants for the substrate specificity.
Disease
Known disease associated with this structure: Ichthyosis with hypotrichosis OMIM:[606797]
About this Structure
1EAW is a Protein complex structure of sequences from Bos taurus and Homo sapiens. Full crystallographic information is available from OCA.
Reference
Catalytic domain structures of MT-SP1/matriptase, a matrix-degrading transmembrane serine proteinase., Friedrich R, Fuentes-Prior P, Ong E, Coombs G, Hunter M, Oehler R, Pierson D, Gonzalez R, Huber R, Bode W, Madison EL, J Biol Chem. 2002 Jan 18;277(3):2160-8. Epub 2001 Nov 5. PMID:11696548
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