1UEA

MMP-3/TIMP-1 COMPLEX

1UEA の概要

• エントリーDOI: 10.2210/pdb1uea/pdb
• 分子名称: MATRIX METALLOPROTEINASE-3, TISSUE INHIBITOR OF METALLOPROTEINASE-1, ZINC ION, ... (5 entities in total)
• 機能のキーワード: proteinase, zinc-endopeptidase, proteinase inhibitor, complex, mmps (matrix metallo proteinases) timps (tissue inhibitor of metallo proteinases), metzincins, complex (metalloprotease-inhibitor), complex (metalloprotease-inhibitor) complex, complex (metalloprotease/inhibitor)
• 由来する生物種: Homo sapiens (human); 詳細
• 細胞内の位置: Secreted, extracellular space, extracellular matrix (Probable): P08254; Secreted: P01033
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 80816.33

構造登録者

Bode, W.,Maskos, K.,Gomis-Rueth, F.-X.,Nagase, H. (登録日: 1997-06-06, 公開日: 1998-10-14, 最終更新日: 2024-10-09)

主引用文献

Gomis-Ruth, F.X.,Maskos, K.,Betz, M.,Bergner, A.,Huber, R.,Suzuki, K.,Yoshida, N.,Nagase, H.,Brew, K.,Bourenkov, G.P.,Bartunik, H.,Bode, W.
Mechanism of inhibition of the human matrix metalloproteinase stromelysin-1 by TIMP-1.
Nature, 389:77-81, 1997

PubMed Abstract: Matrix metalloproteinases (MMPs) are zinc endopeptidases that are required for the degradation of extracellular matrix components during normal embryo development, morphogenesis and tissue remodelling. Their proteolytic activities are precisely regulated by endogenous tissue inhibitors of metalloproteinases (TIMPs). Disruption of this balance results in diseases such as arthritis, atherosclerosis, tumour growth and metastasis. Here we report the crystal structure of an MMP-TIMP complex formed between the catalytic domain of human stromelysin-1 (MMP-3) and human TIMP-1. TIMP-1, a 184-residue protein, has the shape of an elongated, contiguous wedge. With its long edge, consisting of five different chain regions, it occupies the entire length of the active-site cleft of MMP-3. The central disulphide-linked segments Cys 1-Thr 2-Cys 3-Val 4 and Ser 68-Val 69 bind to either side of the catalytic zinc. Cys 1 bidentally coordinates this zinc, and the Thr-2 side chain extends into the large specificity pocket of MMP-3. This unusual architecture of the interface between MMP-3 and TIMP-1 suggests new possibilities for designing TIMP variants and synthetic MMP inhibitors with potential therapeutic applications.

PubMed: 9288970
DOI: 10.1038/37995

実験手法

X-RAY DIFFRACTION (2.8 Å)