The proteolytic activity of matrix metalloproteinases toward extracellular matrix components (ECM), cytokines, chemokines, and membrane receptors is crucial for several homeostatic and pathological processes. Active MMPs are a family of single-chain enzymes (23 family members in the human genome), most of which constituted by a catalytic domain and by a hemopexin-like domain connected by a linker. The X-ray structures of MMP-1 and MMP-2 suggest a conserved and well-defined spatial relationship between the two domains. Here we present structural data for MMP-12, suitably stabilized against self-hydrolysis, both in solution (NMR and SAXS) and in the solid state (X-ray), showing that the hemopexin-like and the catalytic domains experience conformational freedom with respect to each other on a time scale shorter than 10−8 s. Hints on the probable conformations are also obtained. This experimental finding opens new perspectives for the often hypothesized active role of the hemopexin-like domain in the enzymatic activity of MMPs.

Evidence of reciprocal reorientation of the catalytic and hemopexin-like domains of full-length MMP-12 / I. Bertini; V. Calderone; M. Fragai; R. Jaiswal; C. Luchinat; M. Melikian; E. Mylonas; D. I. Svergun. - In: JOURNAL OF THE AMERICAN CHEMICAL SOCIETY. - ISSN 0002-7863. - STAMPA. - 130:(2008), pp. 7011-7021. [10.1021/ja710491y]

Evidence of reciprocal reorientation of the catalytic and hemopexin-like domains of full-length MMP-12

BERTINI, IVANO;CALDERONE, VITO;FRAGAI, MARCO;JAISWAL, RAHUL;LUCHINAT, CLAUDIO;MELIKIAN, MAXIME THIERRY OLIVIER;
2008

Abstract

The proteolytic activity of matrix metalloproteinases toward extracellular matrix components (ECM), cytokines, chemokines, and membrane receptors is crucial for several homeostatic and pathological processes. Active MMPs are a family of single-chain enzymes (23 family members in the human genome), most of which constituted by a catalytic domain and by a hemopexin-like domain connected by a linker. The X-ray structures of MMP-1 and MMP-2 suggest a conserved and well-defined spatial relationship between the two domains. Here we present structural data for MMP-12, suitably stabilized against self-hydrolysis, both in solution (NMR and SAXS) and in the solid state (X-ray), showing that the hemopexin-like and the catalytic domains experience conformational freedom with respect to each other on a time scale shorter than 10−8 s. Hints on the probable conformations are also obtained. This experimental finding opens new perspectives for the often hypothesized active role of the hemopexin-like domain in the enzymatic activity of MMPs.
2008
130
7011
7021
I. Bertini; V. Calderone; M. Fragai; R. Jaiswal; C. Luchinat; M. Melikian; E. Mylonas; D. I. Svergun
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Utilizza questo identificatore per citare o creare un link a questa risorsa: https://hdl.handle.net/2158/354218
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