1ZS0

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

1ZS0 の概要

• エントリーDOI: 10.2210/pdb1zs0/pdb
• 分子名称: Neutrophil collagenase, CALCIUM ION, ZINC ION, ... (6 entities in total)
• 機能のキーワード: phosphonic inhibitor, sulphonamide junction, stereoselective inhibition, hydrolase
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Cytoplasmic granule: P22894
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 18917.35

構造登録者

Pochetti, G.,Gavuzzo, E.,Campestre, C.,Agamennone, M.,Tortorella, P.,Consalvi, V.,Gallina, C.,Hiller, O.,Tschesche, H.,Tucker, P.A.,Mazza, F. (登録日: 2005-05-23, 公開日: 2006-05-02, 最終更新日: 2023-08-23)

主引用文献

Pochetti, G.,Gavuzzo, E.,Campestre, C.,Agamennone, M.,Tortorella, P.,Consalvi, V.,Gallina, C.,Hiller, O.,Tschesche, H.,Tucker, P.A.,Mazza, F.
Structural insight into the stereoselective inhibition of MMP-8 by enantiomeric sulfonamide phosphonates.
J.Med.Chem., 49:923-931, 2006

PubMed Abstract: 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.

PubMed: 16451058
DOI: 10.1021/jm050787+

実験手法

X-RAY DIFFRACTION (1.56 Å)