1zs0
From Proteopedia
(New page: 200px<br /> <applet load="1zs0" size="450" color="white" frame="true" align="right" spinBox="true" caption="1zs0, resolution 1.56Å" /> '''Crystal structure o...) |
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| - | [[Image:1zs0.gif|left|200px]]<br /> | + | [[Image:1zs0.gif|left|200px]]<br /><applet load="1zs0" size="350" color="white" frame="true" align="right" spinBox="true" |
| - | <applet load="1zs0" size=" | + | |
caption="1zs0, resolution 1.56Å" /> | caption="1zs0, resolution 1.56Å" /> | ||
'''Crystal structure of the complex between MMP-8 and a phosphonate inhibitor (S-enantiomer)'''<br /> | '''Crystal structure of the complex between MMP-8 and a phosphonate inhibitor (S-enantiomer)'''<br /> | ||
==Overview== | ==Overview== | ||
| - | Potent and selective inhibitors of matrix metalloproteinases (MMPs), a | + | Potent and selective inhibitors of matrix metalloproteinases (MMPs), a family of zinc proteases that can degrade all the components of the extracellular matrix, could be useful for treatment of diseases such as cancer and arthritis. The most potent MMP inhibitors are based on hydroxamate as zinc-binding group (ZBG). alpha-Arylsulfonylamino phosphonates incorporate a particularly favorable combination of phosphonate as ZBG and arylsulfonylamino backbone so that their affinity exceptionally attains the nanomolar strength frequently observed for hydroxamate analogues. The detailed mode of binding of [1-(4'-methoxybiphenyl-4-sulfonylamino)-2-methylpropyl]phosphonate has been clarified by the crystal structures of the complexes that the R- and S-enantiomers respectively form with MMP-8. The reasons for the preferential MMP-8 inhibition by the R-phosphonate are underlined and the differences in the mode of binding of analogous alpha-arylsulfonylamino hydroxamates and carboxylates are discussed. |
==About this Structure== | ==About this Structure== | ||
| - | 1ZS0 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 CA, ZN, EIN and MES as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Neutrophil_collagenase Neutrophil collagenase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.24.34 3.4.24.34] Full crystallographic information is available from [http:// | + | 1ZS0 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=CA:'>CA</scene>, <scene name='pdbligand=ZN:'>ZN</scene>, <scene name='pdbligand=EIN:'>EIN</scene> and <scene name='pdbligand=MES:'>MES</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Neutrophil_collagenase Neutrophil collagenase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.24.34 3.4.24.34] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1ZS0 OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Tortorella, P.]] | [[Category: Tortorella, P.]] | ||
[[Category: Tschesche, H.]] | [[Category: Tschesche, H.]] | ||
| - | [[Category: Tucker, P | + | [[Category: Tucker, P A.]] |
[[Category: CA]] | [[Category: CA]] | ||
[[Category: EIN]] | [[Category: EIN]] | ||
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[[Category: sulphonamide junction]] | [[Category: sulphonamide junction]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 16:18:32 2008'' |
Revision as of 14:18, 21 February 2008
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Crystal structure of the complex between MMP-8 and a phosphonate inhibitor (S-enantiomer)
Overview
Potent and selective inhibitors of matrix metalloproteinases (MMPs), a family of zinc proteases that can degrade all the components of the extracellular matrix, could be useful for treatment of diseases such as cancer and arthritis. The most potent MMP inhibitors are based on hydroxamate as zinc-binding group (ZBG). alpha-Arylsulfonylamino phosphonates incorporate a particularly favorable combination of phosphonate as ZBG and arylsulfonylamino backbone so that their affinity exceptionally attains the nanomolar strength frequently observed for hydroxamate analogues. The detailed mode of binding of [1-(4'-methoxybiphenyl-4-sulfonylamino)-2-methylpropyl]phosphonate has been clarified by the crystal structures of the complexes that the R- and S-enantiomers respectively form with MMP-8. The reasons for the preferential MMP-8 inhibition by the R-phosphonate are underlined and the differences in the mode of binding of analogous alpha-arylsulfonylamino hydroxamates and carboxylates are discussed.
About this Structure
1ZS0 is a Single protein structure of sequence from Homo sapiens with , , and as ligands. Active as Neutrophil collagenase, with EC number 3.4.24.34 Full crystallographic information is available from OCA.
Reference
Structural insight into the stereoselective inhibition of MMP-8 by enantiomeric sulfonamide phosphonates., Pochetti G, Gavuzzo E, Campestre C, Agamennone M, Tortorella P, Consalvi V, Gallina C, Hiller O, Tschesche H, Tucker PA, Mazza F, J Med Chem. 2006 Feb 9;49(3):923-31. PMID:16451058
Page seeded by OCA on Thu Feb 21 16:18:32 2008
Categories: Homo sapiens | Neutrophil collagenase | Single protein | Agamennone, M. | Campestre, C. | Consalvi, V. | Gallina, C. | Gavuzzo, E. | Hiller, O. | Mazza, F. | Pochetti, G. | Tortorella, P. | Tschesche, H. | Tucker, P A. | CA | EIN | MES | ZN | Phosphonic inhibitor | Stereoselective inhibition | Sulphonamide junction
