Computational Analysis of the Metal Selectivity of Matrix Metalloproteinase 8

Matrix metalloproteinase (MMP) is a class of metalloenzyme that cleaves peptide bonds in extracellular matrices. Their functions are important in both health and disease of animals. Here using quantum mechanics simulations of the MMP8 protein, the coordination chemistry of different metal cofactors is examined. Comparisons found that Jhan-Teller effects in Cu(II) destabilize the wild-type MMP8 but a histidine to glutamine mutation at residue number 197 can potentially allow the MMP8 protein to utilize Cu(II) in reactions. Simulations also demonstrates the requirement of a conformational change in the ligand before enzymatic cleavage. The insights provided in here will assist future protein engineering efforts utilizing the MMP8 protein.