An analysis of the conformational changes that accompany the activation and inhibition of gelatinase A

FEBS Letters

Price, Nicholas C.¹  Crabbe, Thomas²  Kelly, Sharon M.¹ 

[1] Department of Biological and Molecular Sciences, University of Stirling, Stirling FK9 4LA, UK;Discovery Projects, Celltech Therapeutics Ltd., Slough SL1 4EN, UK

关键词: Gelatinase A;    Activation;    TIMP-1;    Inhibition;    MMP;    matrix metalloproteinase;    APMA;    (4-aminophenylmercuric)acetate;    TIMP;    tissue inhibitor of metalloproteinases;    (Δ418-631)progelatinase A;    deletion mutant of progelatinase A lacking amino acids 418-631 (C-terminal domain);    proE375 → A;    active site mutant of progelatinase A;    McaPLGLDpaAR;    (7-methoxycoumarin-4-yl)acetyl-Pro-Leu-Gly-Leu-[3-(2;    4-dinitrophenyl)-l-2;    3-diaminopropionyl]-Ala-Arg-NH2;   

DOI  :  10.1016/0014-5793(96)00005-1

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

The latent precursors of the matrix metalloproteinases (MMPs) are converted by (4-aminophenylmercuric)acetate to active forms that lose their propeptide as a result of autolysis. C.D. and an active site mutant of progelatinase A (MMP2) were used to demonstrate that, although propeptide removal is accompanied by a decrease in the enzyme's β-sheet content, the initial activation is achieved with only minor modifications to the conformation. Mixing activated gelatinase A with the natural inhibitor, TIMP-1, resulted in conformational changes that were absent when a synthetic inhibitor was used. The relevance of these results to MMP activation and inhibition is discussed.

【 授权许可】

Unknown