3DPE

Crystal structure of the complex between MMP-8 and a non-zinc chelating inhibitor

3DPE の概要

• エントリーDOI: 10.2210/pdb3dpe/pdb
• 関連するPDBエントリー: 1UTT 1UTZ 1XUC 1XUD 1XUR 2OW9 2OZR 3DNG 3DPF
• 分子名称: Neutrophil collagenase, CALCIUM ION, ZINC ION, ... (5 entities in total)
• 機能のキーワード: hydrolase, selective inhibition, non-zinc chelating inhibitors, calcium, collagen degradation, extracellular matrix, glycoprotein, metal-binding, metalloprotease, polymorphism, protease, secreted, zinc, zymogen
• 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: 18862.30

構造登録者

Pochetti, G.,Montanari, R.,Mazza, F. (登録日: 2008-07-08, 公開日: 2009-03-03, 最終更新日: 2023-11-01)

主引用文献

Pochetti, G.,Montanari, R.,Gege, C.,Chevrier, C.,Taveras, A.G.,Mazza, F.
Extra Binding Region Induced by Non-Zinc Chelating Inhibitors into the S(1)' Subsite of Matrix Metalloproteinase 8 (MMP-8)
J.Med.Chem., 52:1040-1049, 2009

PubMed Abstract: The mode of binding and the activity of the first two non-zinc chelating, potent, and selective inhibitors of human neutrophil collagenase are reported. The crystal structures of the catalytic domain of MMP-8, respectively complexed with each inhibitor, reveals that both ligands are deeply inserted into the primary specificity subsite S(1)', where they induce a similar conformational change of the surrounding loop that is endowed with the main specificity determinants of MMPs. Accord to this rearrangement, both inhibitors remove the floor of the pocket formed by the Y227 side-chain, rendering available an extra binding region never explored before. The present data show that potent and more selective inhibitors can be obtained by developing ligands able to interact with the selectivity regions of the enzyme rather than with the catalytic zinc ion, which is the common feature of all MMP members.

PubMed: 19173605
DOI: 10.1021/jm801166j

実験手法

X-RAY DIFFRACTION (1.6 Å)