1zs0

From Proteopedia

---

Revision as of 18:33, 12 November 2007

proteopedia linkproteopedia link

spinqualitylabelsall models 1zs0, resolution 1.56Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image

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 CA, ZN, EIN and MES 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 Mon Nov 12 20:39:59 2007