3WV2

Crystal structure of the catalytic domain of MMP-13 complexed with N-(3-methoxybenzyl)-4-oxo-3,4-dihydroquinazoline-2-carboxamide

3WV2 の概要

• エントリーDOI: 10.2210/pdb3wv2/pdb
• 関連するPDBエントリー: 3WV1 3WV3
• 分子名称: Collagenase 3, ZINC ION, CALCIUM ION, ... (6 entities in total)
• 機能のキーワード: hydrolase, 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 (Probable): P45452
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 39557.33

構造登録者

Oki, H.,Tanaka, Y. (登録日: 2014-05-12, 公開日: 2014-09-24, 最終更新日: 2024-05-29)

主引用文献

Nara, H.,Sato, K.,Naito, T.,Mototani, H.,Oki, H.,Yamamoto, Y.,Kuno, H.,Santou, T.,Kanzaki, N.,Terauchi, J.,Uchikawa, O.,Kori, M.
Thieno[2,3-d]pyrimidine-2-carboxamides bearing a carboxybenzene group at 5-position: highly potent, selective, and orally available MMP-13 inhibitors interacting with the S1′′ binding site.
Bioorg.Med.Chem., 22:5487-5505, 2014

PubMed Abstract: On the basis of X-ray co-crystal structures of matrix metalloproteinase-13 (MMP-13) in complex with its inhibitors, our structure-based drug design (SBDD) strategy was directed to achieving high affinity through optimal protein-ligand interaction with the unique S1″ hydrophobic specificity pocket. This report details the optimization of lead compound 44 to highly potent and selective MMP-13 inhibitors based on fused pyrimidine scaffolds represented by the thienopyrimidin-4-one 26c. Furthermore, we have examined the release of collagen fragments from bovine nasal cartilage in response to a combination of IL-1 and oncostatin M.

PubMed: 25192810
DOI: 10.1016/j.bmc.2014.07.025

実験手法

X-RAY DIFFRACTION (2.3 Å)