Insight towards the conserved water mediated recognition of catalytic and structural Zn+2 ions in human Matrix Metalloproteinase-8 enzyme: A study by MD-simulation methods

Human matrix metalloproteinase-8 (hMMP-8) plays a important role in the progression of colorectal cancer, metastasis, multiple sclerosis and rheumetoid arthritis. Extensive MD-simulation of the PDB and solvated structures of hMMP-8 has revealed the presence of few conserved water molecules around the catalytic and structural zinc (Zn-C and Zn-S) ions. The coordination of two conserved water molecules (W and W-S) to ZnS and the H-bonding interaction of W-S to S-151 have indicated the plausible involvement of that metal ion in the catalytic process. Beside this the coupling of Zn-C and Zn-S metal ions (Zn-C - W-H (W-1)..... W-2.... H-162 - Zn-S) through two conserved hydrophilic centers (occupied by water molecules) may also provide some rational on the recognition of two zinc ions which were separated by similar to 13 angstrom in their X-ray structures. This unique recognition of both the Zn+2 ions in the enzyme through conserved water molecules may be implemented/exploited for the design of antiproteolytic agent using water mimic drug design protocol.