2usn
From Proteopedia
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| - | [[Image:2usn.jpg|left|200px]]<br /><applet load="2usn" size=" | + | [[Image:2usn.jpg|left|200px]]<br /><applet load="2usn" size="350" color="white" frame="true" align="right" spinBox="true" |
caption="2usn, resolution 2.2Å" /> | caption="2usn, resolution 2.2Å" /> | ||
'''CRYSTAL STRUCTURE OF THE CATALYTIC DOMAIN OF HUMAN FIBROBLAST STROMELYSIN-1 INHIBITED WITH THIADIAZOLE INHIBITOR PNU-141803'''<br /> | '''CRYSTAL STRUCTURE OF THE CATALYTIC DOMAIN OF HUMAN FIBROBLAST STROMELYSIN-1 INHIBITED WITH THIADIAZOLE INHIBITOR PNU-141803'''<br /> | ||
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==About this Structure== | ==About this Structure== | ||
| - | 2USN 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 ZN, CA and IN8 as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Stromelysin_1 Stromelysin 1], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.24.17 3.4.24.17] Known structural/functional Sites: <scene name='pdbsite=INH:Site Inh Is The Binding Site For The Amide-Thiadiazole I ...'>INH</scene>, <scene name='pdbsite=ZN1:Zn1 Are The Ligands Of Catalytic (Zn 257) Zn Ion'>ZN1</scene> and <scene name='pdbsite=ZN2:Zn2 Are The Ligands Of Structural (Zn 258) Zn Ion'>ZN2</scene>. Full crystallographic information is available from [http:// | + | 2USN 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=ZN:'>ZN</scene>, <scene name='pdbligand=CA:'>CA</scene> and <scene name='pdbligand=IN8:'>IN8</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Stromelysin_1 Stromelysin 1], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.24.17 3.4.24.17] Known structural/functional Sites: <scene name='pdbsite=INH:Site+Inh+Is+The+Binding+Site+For+The+Amide-Thiadiazole+I+...'>INH</scene>, <scene name='pdbsite=ZN1:Zn1+Are+The+Ligands+Of+Catalytic+(Zn+257)+Zn+Ion'>ZN1</scene> and <scene name='pdbsite=ZN2:Zn2+Are+The+Ligands+Of+Structural+(Zn+258)+Zn+Ion'>ZN2</scene>. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2USN OCA]. |
==Reference== | ==Reference== | ||
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[[Category: metalloprotease]] | [[Category: metalloprotease]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Feb 3 10:47:01 2008'' |
Revision as of 08:47, 3 February 2008
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CRYSTAL STRUCTURE OF THE CATALYTIC DOMAIN OF HUMAN FIBROBLAST STROMELYSIN-1 INHIBITED WITH THIADIAZOLE INHIBITOR PNU-141803
Contents |
Overview
The binding of two 5-substituted-1,3,4-thiadiazole-2-thione inhibitors to, the matrix metalloproteinase stromelysin (MMP-3) have been characterized, by protein crystallography. Both inhibitors coordinate to the catalytic, zinc cation via an exocyclic sulfur and lay in an unusual position across, the unprimed (P1-P3) side of the proteinase active site. Nitrogen atoms in, the thiadiazole moiety make specific hydrogen bond interactions with, enzyme structural elements that are conserved across all enzymes in the, matrix metalloproteinase class. Strong hydrophobic interactions between, the inhibitors and the side chain of tyrosine-155 appear to be responsible, for the very high selectivity of these inhibitors for stromelysin. In, these enzyme/inhibitor complexes, the S1' enzyme subsite is unoccupied. A, conformational rearrangement of the catalytic domain occurs that reveals, an inherent flexibility of the substrate binding region leading to, speculation about a possible mechanism for modulation of stromelysin, activity and selectivity.
Disease
Known diseases associated with this structure: Coronary heart disease, susceptibility to OMIM:[185250]
About this Structure
2USN is a Single protein structure of sequence from Homo sapiens with , and as ligands. Active as Stromelysin 1, with EC number 3.4.24.17 Known structural/functional Sites: , and . Full crystallographic information is available from OCA.
Reference
Structural characterizations of nonpeptidic thiadiazole inhibitors of matrix metalloproteinases reveal the basis for stromelysin selectivity., Finzel BC, Baldwin ET, Bryant GL Jr, Hess GF, Wilks JW, Trepod CM, Mott JE, Marshall VP, Petzold GL, Poorman RA, O'Sullivan TJ, Schostarez HJ, Mitchell MA, Protein Sci. 1998 Oct;7(10):2118-26. PMID:9792098
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