title: Structural basis for matrix metalloproteinase 1-catalyzed collagenolysis.
abstract: 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-substrate 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 782-785). 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 "closed" 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.
authors.affiliation: Magnetic Resonance Center (CERM), University of Florence, Via L. Sacconi 6, 50019 Sesto Fiorentino, Italy. bertini@cerm.unifi.it
authors.forename: Ivano
authors.initials: I
authors.lastname: Bertini
authors.forename: Marco
authors.initials: M
authors.lastname: Fragai
authors.forename: Claudio
authors.initials: C
authors.lastname: Luchinat
authors.forename: Maxime
authors.initials: M
authors.lastname: Melikian
authors.forename: Mirco
authors.initials: M
authors.lastname: Toccafondi
authors.forename: Janelle L
authors.initials: JL
authors.lastname: Lauer
authors.forename: Gregg B
authors.initials: GB
authors.lastname: Fields
mesh_terms: D055162:Biocatalysis; D003094:Collagen / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism*; D020781:Matrix Metalloproteinase 1 / Q000737:chemistry / Q000378:metabolism*; D008958:Models, Molecular; D019906:Nuclear Magnetic Resonance, Biomolecular; D011487:Protein Conformation
chemical_list: D003094:Collagen; D020781:Matrix Metalloproteinase 1