2USN

CRYSTAL STRUCTURE OF THE CATALYTIC DOMAIN OF HUMAN FIBROBLAST STROMELYSIN-1 INHIBITED WITH THIADIAZOLE INHIBITOR PNU-141803

2USN の概要

• エントリーDOI: 10.2210/pdb2usn/pdb
• 分子名称: STROMELYSIN-1, ZINC ION, CALCIUM ION, ... (5 entities in total)
• 機能のキーワード: hydrolase, metalloprotease, fibroblast, collagen degradation
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Secreted, extracellular space, extracellular matrix : P08254
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 19326.65

構造登録者

Finzel, B.C.,Bryant Junior, G.L.,Baldwin, E.T. (登録日: 1998-06-09, 公開日: 1998-12-23, 最終更新日: 2024-05-22)

主引用文献

Finzel, B.C.,Baldwin, E.T.,Bryant Jr., G.L.,Hess, G.F.,Wilks, J.W.,Trepod, C.M.,Mott, J.E.,Marshall, V.P.,Petzold, G.L.,Poorman, R.A.,O'Sullivan, T.J.,Schostarez, H.J.,Mitchell, M.A.
Structural characterizations of nonpeptidic thiadiazole inhibitors of matrix metalloproteinases reveal the basis for stromelysin selectivity.
Protein Sci., 7:2118-2126, 1998

PubMed Abstract: The binding of two 5-substituted-1,3,4-thiadiazole-2-thione inhibitors to the matrix metalloproteinase stromelysin (MMP-3) have been characterized by protein crystallography. Both inhibitors coordinate to the catalytic zinc cation via an exocyclic sulfur and lay in an unusual position across the unprimed (P1-P3) side of the proteinase active site. Nitrogen atoms in the thiadiazole moiety make specific hydrogen bond interactions with enzyme structural elements that are conserved across all enzymes in the matrix metalloproteinase class. Strong hydrophobic interactions between the inhibitors and the side chain of tyrosine-155 appear to be responsible for the very high selectivity of these inhibitors for stromelysin. In these enzyme/inhibitor complexes, the S1' enzyme subsite is unoccupied. A conformational rearrangement of the catalytic domain occurs that reveals an inherent flexibility of the substrate binding region leading to speculation about a possible mechanism for modulation of stromelysin activity and selectivity.

PubMed: 9792098

実験手法

X-RAY DIFFRACTION (2.2 Å)