Structural Basis for Matrix Metalloproteinase 1-Catalyzed Collagenolysis

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• 作者：Ivano Bertini ; Marco Fragai ; Claudio Luchinat ; Maxime Melikian ; Mirco Toccafondi ; Janelle L. Lauer ; Gregg B. Fields
• 刊名：The Journal of the American Chemical Society
• 出版年：2012
• 出版时间：February 1, 2012
• 年：2012
• 卷：134
• 期：4
• 页码：2100-2110
• 全文大小：528K
• 年卷期：v.134,no.4(February 1, 2012)
• ISSN：1520-5126

文摘

The proteolysis of collagen triple-helical structure (collagenolysis) is a poorly understood yet critical physiological process. Presently, matrix metalloproteinase 1 (MMP-1) and collagen triple-helical peptide models have been utilized to characterize the events and calculate the energetics of collagenolysis via NMR spectroscopic analysis of 12 enzyme鈥搒ubstrate complexes. The triple-helix is bound initially by the MMP-1 hemopexin-like (HPX) domain via a four amino acid stretch (analogous to type I collagen residues 782鈥?85). The triple-helix is then presented to the MMP-1 catalytic (CAT) domain in a distinct orientation. The HPX and CAT domains are rotated with respect to one another compared with the X-ray 鈥渃losed鈥?conformation of MMP-1. Back-rotation of the CAT and HPX domains to the X-ray closed conformation releases one chain out of the triple-helix, and this chain is properly positioned in the CAT domain active site for subsequent hydrolysis. The aforementioned steps provide a detailed, experimentally derived, and energetically favorable collagenolytic mechanism, as well as significant insight into the roles of distinct domains in extracellular protease function.