1zvx: Difference between revisions

Revision as of 18:08, 3 May 2008

Crystal structure of the complex between MMP-8 and a phosphonate inhibitor (R-enantiomer)

OverviewOverview

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 StructureAbout this Structure

1ZVX is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.

ReferenceReference

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 Sat May 3 18:08:36 2008

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OCA

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 [[Image:1zvx.gif|left|200px]]
- {{Structure
+<!--
-|PDB= 1zvx |SIZE=350|CAPTION= <scene name='initialview01'>1zvx</scene>, resolution 1.87&Aring;
+The line below this paragraph, containing "STRUCTURE_1zvx", creates the "Structure Box" on the page.
-|SITE=
+You may change the PDB parameter (which sets the PDB file loaded into the applet)
-|LIGAND= <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=FIN:(1R)-1-{[(4&#39;-METHOXY-1,1&#39;-BIPHENYL-4-YL)SULFONYL]AMINO}-2-METHYLPROPYLPHOSPHONIC+ACID'>FIN</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene>
+or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
-|ACTIVITY= <span class='plainlinks'>[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] </span>
+or leave the SCENE parameter empty for the default display.
-|GENE= MMP8, CLG1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])
+-->
-|DOMAIN=
+{{STRUCTURE_1zvx|  PDB=1zvx  |  SCENE=  }}
-|RELATEDENTRY=[[1zs0|1ZS0]]
-|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1zvx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1zvx OCA], [http://www.ebi.ac.uk/pdbsum/1zvx PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1zvx RCSB]</span>
-}}
 '''Crystal structure of the complex between MMP-8 and a phosphonate inhibitor (R-enantiomer)'''
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 [[Category: Tschesche, H.]]
 [[Category: Tucker, P A.]]
-[[Category: hydrolase]]
+[[Category: Hydrolase]]
-[[Category: phosphonic inhibitor]]
+[[Category: Phosphonic inhibitor]]
-[[Category: stereoselective inhibition]]
+[[Category: Stereoselective inhibition]]
-[[Category: sulfonamide junction]]
+[[Category: Sulfonamide junction]]
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May  3 18:08:36 2008''
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 01:42:19 2008''