3N2V

Crystal structure of the catalytic domain of human MMP12 complexed with the inhibitor N-hydroxy-2-(N-hydroxyethyl)biphenyl-4-ylsulfonamido)acetamide

3N2V の概要

• エントリーDOI: 10.2210/pdb3n2v/pdb
• 関連するPDBエントリー: 3F15 3F16 3F17 3N2U
• 分子名称: Macrophage metalloelastase, ZINC ION, CALCIUM ION, ... (5 entities in total)
• 機能のキーワード: matrix metalloproteinase, mmp12, elastase, complex (elastase-inhibitor), metallo elastase, extracellular matrix, glycoprotein, hydrolase, metal-inding, metalloprotease, protease, secreted, zymogen, hydrolase-hydrolase inhibitor complex, hydrolase/hydrolase inhibitor
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Secreted, extracellular space, extracellular matrix : P39900
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 18085.92

構造登録者

Calderone, V. (登録日: 2010-05-19, 公開日: 2010-11-10, 最終更新日: 2023-09-06)

主引用文献

Attolino, E.,Calderone, V.,Dragoni, E.,Fragai, M.,Richichi, B.,Luchinat, C.,Nativi, C.
Structure-based approach to nanomolar, water soluble matrix metalloproteinases inhibitors (MMPIs).
Eur.J.Med.Chem., 45:5919-5925, 2010

PubMed Abstract: N-arylsulfonyl-based MMPs inhibitors (MMPIs) are among the most prominent inhibitors possessing nanomolar affinity. However, their poor bioavailability remains critical for the drug development of this family of molecules. The structural analysis of the complex of NNGH (the most representative member of the family) with MMP-12 provided us with the basis to effectively design simple NNGH analogues with enhanced solubility in water. Following this approach, the sec-butyl residue, not directly involved in the binding with MMP, has been replaced with hydrophilic residues thus yielding new potent inhibitors soluble in water.

PubMed: 20965620
DOI: 10.1016/j.ejmech.2010.09.057

実験手法

X-RAY DIFFRACTION (1.55 Å)