Exploration of the zinc finger motif in controlling activity of matrix metalloproteinases.

ABSTRACT: Discovering ways to control the activity of matrix metalloproteinases (MMPs), zinc-dependent enzymes capable of degrading extracellular matrix proteins, is an important field of cancer research. We report here a novel strategy for assembling MMP inhibitors on the basis of oligopeptide ligands by exploring the pattern known as the zinc finger motif. Advanced molecular modeling tools were used to characterize the structural binding motifs of experimentally tested MMP inhibitors, as well as those of newly proposed peptidomimetics, in their zinc-containing active sites. The results of simulations based on the quantum mechanics/molecular mechanics (QM/MM) approach and Car-Parrinello molecular dynamics with QM/MM potentials demonstrate that, upon binding of Regasepin1, a known MMP-9 inhibitor, t

SUBMITTER: Khrenova MG 

PROVIDER: S-EPMC4254000 | biostudies-literature | 2014 Nov

REPOSITORIES: biostudies-literature