3KEJ

Crystal Structure of Human MMP-13 complexed with a (pyridin-4-yl)-2H-tetrazole compound

3KEJ の概要

• エントリーDOI: 10.2210/pdb3kej/pdb
• 関連するPDBエントリー: 3KEC 3KEK
• 分子名称: Collagenase 3, ZINC ION, CALCIUM ION, ... (5 entities in total)
• 機能のキーワード: s1' inhibitor, selective mmp-13 inhibitor, s1' specificity pocket, no contact to zn, collagen degradation, disease mutation, disulfide bond, extracellular matrix, glycoprotein, hydrolase, metal-binding, 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 (Probable): P45452
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 38926.84

構造登録者

Shieh, H.-S.,Collins, B.,Schnute, M.E. (登録日: 2009-10-26, 公開日: 2010-11-10, 最終更新日: 2024-02-21)

主引用文献

Schnute, M.E.,O'Brien, P.M.,Nahra, J.,Morris, M.,Howard Roark, W.,Hanau, C.E.,Ruminski, P.G.,Scholten, J.A.,Fletcher, T.R.,Hamper, B.C.,Carroll, J.N.,Patt, W.C.,Shieh, H.S.,Collins, B.,Pavlovsky, A.G.,Palmquist, K.E.,Aston, K.W.,Hitchcock, J.,Rogers, M.D.,McDonald, J.,Johnson, A.R.,Munie, G.E.,Wittwer, A.J.,Man, C.F.,Settle, S.L.,Nemirovskiy, O.,Vickery, L.E.,Agawal, A.,Dyer, R.D.,Sunyer, T.
Discovery of (pyridin-4-yl)-2H-tetrazole as a novel scaffold to identify highly selective matrix metalloproteinase-13 inhibitors for the treatment of osteoarthritis.
Bioorg.Med.Chem.Lett., 20:576-580, 2010

PubMed Abstract: Potent, highly selective and orally-bioavailable MMP-13 inhibitors have been identified based upon a (pyridin-4-yl)-2H-tetrazole scaffold. Co-crystal structure analysis revealed that the inhibitors bind at the S(1)(') active site pocket and are not ligands for the catalytic zinc atom. Compound 29b demonstrated reduction of cartilage degradation biomarker (TIINE) levels associated with cartilage protection in a preclinical rat osteoarthritis model.

PubMed: 20005097
DOI: 10.1016/j.bmcl.2009.11.081

実験手法

X-RAY DIFFRACTION (2.3 Å)