1D2B

THE MMP-INHIBITORY, N-TERMINAL DOMAIN OF HUMAN TISSUE INHIBITOR OF METALLOPROTEINASES-1 (N-TIMP-1), SOLUTION NMR, 29 STRUCTURES

1D2B の概要

• エントリーDOI: 10.2210/pdb1d2b/pdb
• NMR情報: BMRB: 5154
• 分子名称: Metalloproteinase inhibitor 1 (1 entity in total)
• 機能のキーワード: ob-fold, beta barrel, protease inhibitor, mmp inhibitor, hydrolase inhibitor
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Secreted: P01033
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 14269.31

構造登録者

Wu, B.,Arumugam, S.,Semenchenko, V.,Brew, K.,Van Doren, S.R. (登録日: 1999-09-22, 公開日: 1999-12-22, 最終更新日: 2024-11-20)

主引用文献

Wu, B.,Arumugam, S.,Gao, G.,Lee, G.I.,Semenchenko, V.,Huang, W.,Brew, K.,Van Doren, S.R.
NMR structure of tissue inhibitor of metalloproteinases-1 implicates localized induced fit in recognition of matrix metalloproteinases.
J.Mol.Biol., 295:257-268, 2000

PubMed Abstract: A high quality solution structure of the matrix metalloproteinase inhibitory N-terminal domain of recombinant human tissue inhibitor of metalloproteinases-1 (N-TIMP-1) has been determined. For the rigidly packed residues, the average RMSD to the mean structure is 0. 57 A for the backbone atoms and 1.00 A for all heavy atoms. Comparison of the solution structure of free N-TIMP-1 with the crystal structure of TIMP-1 bound to the catalytic domain of MMP-3 ( Gomis-R]uth et al., 1997 ) shows that the structural core of the beta barrel flanked by helices is nearly unchanged by the association with MMP-3, evident from a backbone RMSD of 1.15 A. However, clear differences in the conformation of the MMP-binding ridge of free and MMP-bound TIMP-1 suggest induced fit throughout the ridge. The MMP-dependent conformational changes in the ridge include a dramatic bending of AB loop residues Glu28 through Leu34, moderate hinge bending of the CD-loop about residues Ala65 and Cys70, and modest bending of the Cys1 through Pro6 segment. A large number of interresidue Nuclear Overhauser enhancements (NOEs) augmented by stereospecific assignments, torsion restraints, and dipolar couplings (an average of 18 non-trivial restraints per residue) engender confidence in these structural inferences. A tight cluster of three lysine residues and one arginine residue atop beta-strands A and B, and identical among TIMP sequences, form the heart of a highly conserved electropositive patch that may interact with anionic components of the extracellular matrix.

PubMed: 10623524
DOI: 10.1006/jmbi.1999.3362

実験手法

SOLUTION NMR