1GXD

proMMP-2/TIMP-2 complex

1GXD の概要

• エントリーDOI: 10.2210/pdb1gxd/pdb
• 関連するPDBエントリー: 1BR9 1CK7 1CXW 1EAK 1GEN 1J7M 1KS0 1RTG 2TMP
• 分子名称: 72 KDA TYPE IV COLLAGENASE, METALLOPROTEINASE INHIBITOR 2, SULFATE ION, ... (5 entities in total)
• 機能のキーワード: hydrolase, metalloprotease, zymogen, collagen degradation, extracellular matrix, gelatinase a, matrix metalloproteinase 2, proteinase inhibitor
• 由来する生物種: HOMO SAPIENS (HUMAN); 詳細
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 186090.81

構造登録者

Morgunova, E.,Tuuttila, A.,Bergmann, U.,Tryggvason, K. (登録日: 2002-04-02, 公開日: 2002-07-09, 最終更新日: 2024-10-23)

主引用文献

Morgunova, E.,Tuuttila, A.,Bergmann, U.,Tryggvason, K.
Structural Insight Into the Complex Formation of Latent Matrix Metalloproteinase 2 with Tissue Inhibitor of Metalloproteinase 2
Proc.Natl.Acad.Sci.USA, 99:7414-, 2002

PubMed Abstract: Matrix metalloproteinases (MMPs) are a family of multidomain enzymes involved in the physiological degradation of connective tissue, as well as in pathological states such as tumor invasion and arthritis. Apart from transcriptional regulation, MMPs are controlled by proenzyme activation and a class of specific tissue inhibitors of metalloproteinases (TIMPs) that bind to the catalytic site. TIMP-2 is a potent inhibitor of MMPs, but it has also been implicated in a unique cell surface activation mechanism of latent MMP-2/gelatinase A/type IV collagenase (proMMP-2), through its binding to the hemopexin domain of proMMP-2 on the one hand and to a membrane-type MMP activator on the other. The present crystal structure of the human proMMP-2/TIMP-2 complex reveals an interaction between the hemopexin domain of proMMP-2 and the C-terminal domain of TIMP-2, leaving the catalytic site of MMP-2 and the inhibitory site of TIMP-2 distant and spatially isolated. The interfacial contact of these two proteins is characterized by two distinct binding regions composed of alternating hydrophobic and hydrophilic interactions. This unique structure provides information for how specificity for noninhibitory MMP/TIMP complex formation is achieved.

PubMed: 12032297
DOI: 10.1073/PNAS.102185399

実験手法

X-RAY DIFFRACTION (3.1 Å)