1cxv
STRUCTURE OF RECOMBINANT MOUSE COLLAGENASE-3 (MMP-13)
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OverviewOverview
The matrix metalloproteinases are crucial in the physiological and, pathological degradation of the mammalian extracellular matrix, including, breast tumours, and osteoarthritic cartilage. These enzymes are classified, according to their matrix substrate specificity. Collagenase-3 (MMP-13) is, a member of this family and preferentially cleaves type II collagen, cartilage, fibronectin and aggrecan. Collagenase-3 is normally expressed, in hypertrophic chondrocytes, periosteal cells, and osteoblasts during, bone development. The structure of the catalytic domain of recombinant, mouse collagenase-3, complexed to the hydroxamate inhibitor (RS-113456), is reported at 2.0 A resolution. Molecular replacement and weak phasing, information from a single derivative determined the structure. Neither, molecular replacement nor derivative methods had a sufficient radius of, convergence to yield a refinable structure. The structure illuminates the, atomic zinc ion interactions with functional groups in the active site, emphasizing zinc ligation and the very voluminous hydrophobic P1' group, for the inhibitor potency. The structure provides insight into the, specificity of this enzyme, facilitating design of specific inhibitors to, target various diseases.
About this StructureAbout this Structure
1CXV is a Single protein structure of sequence from Mus musculus with ZN, CA and CBP as ligands. Full crystallographic information is available from OCA.
ReferenceReference
Structure of recombinant mouse collagenase-3 (MMP-13)., Botos I, Meyer E, Swanson SM, Lemaitre V, Eeckhout Y, Meyer EF, J Mol Biol. 1999 Oct 1;292(4):837-44. PMID:10525409
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