2aig
From Proteopedia
(New page: 200px<br /><applet load="2aig" size="450" color="white" frame="true" align="right" spinBox="true" caption="2aig, resolution 2.6Å" /> '''ADAMALYSIN II WITH PE...) |
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| - | [[Image:2aig.jpg|left|200px]]<br /><applet load="2aig" size=" | + | [[Image:2aig.jpg|left|200px]]<br /><applet load="2aig" size="350" color="white" frame="true" align="right" spinBox="true" |
caption="2aig, resolution 2.6Å" /> | caption="2aig, resolution 2.6Å" /> | ||
'''ADAMALYSIN II WITH PEPTIDOMIMETIC INHIBITOR POL647'''<br /> | '''ADAMALYSIN II WITH PEPTIDOMIMETIC INHIBITOR POL647'''<br /> | ||
==Overview== | ==Overview== | ||
| - | Crotalus adamanteus snake venom adamalysin II is the structural prototype | + | Crotalus adamanteus snake venom adamalysin II is the structural prototype of the adamalysin or ADAM family comprising proteolytic domains of snake venom metalloproteinases, multimodular mammalian reproductive tract proteins, and tumor necrosis factor alpha convertase, TACE, involved in the release of the inflammatory cytokine, TNFalpha. The structure of adamalysin II in noncovalent complex with two small-molecule right-hand side peptidomimetic inhibitors (Pol 647 and Pol 656) has been solved using X-ray diffraction data up to 2.6 and 2.8 A resolution. The inhibitors bind to the S'-side of the proteinase, inserting between two protein segments, establishing a mixed parallel-antiparallel three-stranded beta-sheet and coordinate the central zinc ion in a bidentate manner via their two C-terminal oxygen atoms. The proteinase-inhibitor complexes are described in detail and are compared with other known structures. An adamalysin-based model of the active site of TACE reveals that these small molecules would probably fit into the active site cleft of this latter metalloproteinase, providing a starting model for the rational design of TACE inhibitors. |
==About this Structure== | ==About this Structure== | ||
| - | 2AIG is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Crotalus_adamanteus Crotalus adamanteus] with ZN, CA and SO4 as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Adamalysin Adamalysin], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.24.46 3.4.24.46] Full crystallographic information is available from [http:// | + | 2AIG is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Crotalus_adamanteus Crotalus adamanteus] with <scene name='pdbligand=ZN:'>ZN</scene>, <scene name='pdbligand=CA:'>CA</scene> and <scene name='pdbligand=SO4:'>SO4</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Adamalysin Adamalysin], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.24.46 3.4.24.46] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2AIG OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Crotalus adamanteus]] | [[Category: Crotalus adamanteus]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
| - | [[Category: Gomis-Rueth, F | + | [[Category: Gomis-Rueth, F X.]] |
| - | [[Category: Kress, L | + | [[Category: Kress, L F.]] |
| - | [[Category: Meyer, E | + | [[Category: Meyer, E F.]] |
[[Category: Politi, V.]] | [[Category: Politi, V.]] | ||
[[Category: CA]] | [[Category: CA]] | ||
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[[Category: zinc protease]] | [[Category: zinc protease]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 16:27:45 2008'' |
Revision as of 14:27, 21 February 2008
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ADAMALYSIN II WITH PEPTIDOMIMETIC INHIBITOR POL647
Overview
Crotalus adamanteus snake venom adamalysin II is the structural prototype of the adamalysin or ADAM family comprising proteolytic domains of snake venom metalloproteinases, multimodular mammalian reproductive tract proteins, and tumor necrosis factor alpha convertase, TACE, involved in the release of the inflammatory cytokine, TNFalpha. The structure of adamalysin II in noncovalent complex with two small-molecule right-hand side peptidomimetic inhibitors (Pol 647 and Pol 656) has been solved using X-ray diffraction data up to 2.6 and 2.8 A resolution. The inhibitors bind to the S'-side of the proteinase, inserting between two protein segments, establishing a mixed parallel-antiparallel three-stranded beta-sheet and coordinate the central zinc ion in a bidentate manner via their two C-terminal oxygen atoms. The proteinase-inhibitor complexes are described in detail and are compared with other known structures. An adamalysin-based model of the active site of TACE reveals that these small molecules would probably fit into the active site cleft of this latter metalloproteinase, providing a starting model for the rational design of TACE inhibitors.
About this Structure
2AIG is a Single protein structure of sequence from Crotalus adamanteus with , and as ligands. Active as Adamalysin, with EC number 3.4.24.46 Full crystallographic information is available from OCA.
Reference
Structures of adamalysin II with peptidic inhibitors. Implications for the design of tumor necrosis factor alpha convertase inhibitors., Gomis-Ruth FX, Meyer EF, Kress LF, Politi V, Protein Sci. 1998 Feb;7(2):283-92. PMID:9521103
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