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Publication Abstract from PubMed

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.,Bertini I, Calderone V, Fragai M, Jaiswal R, Luchinat C, Melikian M, Mylonas E, Svergun DI J Am Chem Soc. 2008 May 9;. PMID:18465858^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.