Crystal structures of MMP-1 and -13 reveal the structural basis for selectivity of collagenase inhibitors.

Article Details

Citation

Lovejoy B, Welch AR, Carr S, Luong C, Broka C, Hendricks RT, Campbell JA, Walker KA, Martin R, Van Wart H, Browner MF

Crystal structures of MMP-1 and -13 reveal the structural basis for selectivity of collagenase inhibitors.

Nat Struct Biol. 1999 Mar;6(3):217-21.

PubMed ID
10074939 [ View in 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.

DrugBank Data that Cites this Article

Polypeptides
NameUniProt ID
Collagenase 3P45452Details