966C

CRYSTAL STRUCTURE OF FIBROBLAST COLLAGENASE-1 COMPLEXED TO A DIPHENYL-ETHER SULPHONE BASED HYDROXAMIC ACID

Summary for 966C

• Entry DOI: 10.2210/pdb966c/pdb
• Descriptor: MMP-1, ZINC ION, CALCIUM ION, ... (5 entities in total)
• Functional Keywords: matrix metalloprotease
• Biological source: Homo sapiens (human)
• Cellular location: Secreted, extracellular space, extracellular matrix : P03956
• Total number of polymer chains: 1
• Total formula weight: 18261.66

Authors

Lovejoy, B.,Welch, A.,Carr, S.,Luong, C.,Broka, C.,Hendricks, R.T.,Campbell, J.,Walker, K.,Martin, R.,Van Wart, H.,Browner, M.F. (deposition date: 1998-08-07, release date: 1999-08-07, Last modification date: 2024-02-14)

Primary citation

Lovejoy, B.,Welch, A.R.,Carr, S.,Luong, C.,Broka, C.,Hendricks, R.T.,Campbell, J.A.,Walker, K.A.,Martin, R.,Van Wart, H.,Browner, M.F.
Crystal structures of MMP-1 and -13 reveal the structural basis for selectivity of collagenase inhibitors.
Nat.Struct.Biol., 6:217-221, 1999

PubMed Abstract: The X-ray crystal structures of the catalytic domain of human collagenase-3 (MMP-13) and collagenase-1 (MMP-1) with bound inhibitors provides a basis for understanding the selectivity profile of a novel series of matrix metalloprotease (MMP) inhibitors. Differences in the relative size and shape of the MMP S1' pockets suggest that this pocket is a critical determinant of MMP inhibitor selectivity. The collagenase-3 S1' pocket is long and open, easily accommodating large P1' groups, such as diphenylether. In contrast, the collagenase-1 S1' pocket must undergo a conformational change to accommodate comparable P1' groups. The selectivity of the diphenylether series of inhibitors for collagenase-3 is largely determined by their affinity for the preformed S1' pocket of collagenase-3, as compared to the induced fit in collagenase-1.

PubMed: 10074939
DOI: 10.1038/6657

Experimental method

X-RAY DIFFRACTION (1.9 Å)