1zs0
Crystal structure of the complex between MMP-8 and a phosphonate inhibitor (S-enantiomer)
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| , resolution 1.56Å | |||||||
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| Ligands: | , , and | ||||||
| Gene: | MMP8, CLG1 (Homo sapiens) | ||||||
| Activity: | Neutrophil collagenase, with EC number 3.4.24.34 | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
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
1ZS0 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
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