| Autor: |
Lovejoy, Brett, Welch, Anthony R., Carr, Steven, Luong, Christine, Broka, Chris, Hendricks, R. Than, Campbell, Jeffery A., Walker, Keith A.M., Martin, Robert, Van Wart, Harold, Browner, Michelle F. |
| Předmět: |
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| Zdroj: |
Nature Structural Biology; Mar1999, Vol. 6 Issue 3, p217, 5p |
| Abstrakt: |
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. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
| Externí odkaz: |
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