1cgf
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CRYSTAL STRUCTURES OF RECOMBINANT 19-KDA HUMAN FIBROBLAST COLLAGENASE COMPLEXED TO ITSELF
OverviewOverview
Collagenase is a member of the matrix metalloproteinase (MMP) family of, enzymes. Aberrant regulation of this family has been implicated in, pathologies such as arthritis and metastasis. Two crystal forms of the, catalytic (19-kDa) domain of human fibroblast collagenase have been, determined using collagenase complexed with a peptide-based inhibitor, (CPLX) as a starting model [Lovejoy et al. (1994) Science 263, 375]. The, first crystal form (CF1) contains one molecule in the asymmetric unit and, has been determined at 1.9-A resolution with an R factor of 19.8%. The, second crystal form (CF2) contains two molecules (A and B) in the, asymmetric unit and has been determined at 2.1-A resolution with an R, factor of 19.7%. The catalytic domain of collagenase is spherical with an, active site cleft that contains a ligated catalytic zinc ion. Collagenase, shares some structural homology with the bacterial zinc proteinase, thermolysin [Matthews et al. (1972) Nature, New Biol. 238, 37], and the, crayfish digestive peptidase, astacin [Bode et al. (1992) Nature 358, 164]. The amino terminus (Leu 102 to Gly 105) of CF1 and CF2 molecules A, and B differs from the conformation found in CPLX by bending away from the, molecule and interacting with the active site cleft of symmetry-related, molecules. In this alternative conformation, both the mainchain nitrogen, and carbonyl oxygen of Leu 102 ligate the symmetry-related catalytic zinc., Although there are structural differences in the active site clefts of, CF1, CF2, and CPLX, a number of complex-stabilizing interactions are, conserved. The structure of collagenase will be useful for developing, compounds that selectively inhibit individual members of the closely, related matrix metalloproteinase family.
DiseaseDisease
Known diseases associated with this structure: COPD, rate of decline of lung function in OMIM:[120353]
About this StructureAbout this Structure
1CGF is a Single protein structure of sequence from Homo sapiens with and as ligands. Active as Interstitial collagenase, with EC number 3.4.24.7 Full crystallographic information is available from OCA.
ReferenceReference
Crystal structures of recombinant 19-kDa human fibroblast collagenase complexed to itself., Lovejoy B, Hassell AM, Luther MA, Weigl D, Jordan SR, Biochemistry. 1994 Jul 12;33(27):8207-17. PMID:8031754
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