Understanding the dynamics and reactivity of metalloproteins using computer simulation techniques

DIEGO M. MORENO

Göttingen

Workshop; Workshop of the German-Argentine Univeristy Centre.; 2013

In the past years, computer simulation techniques have proved to be very useful to understand the dynamics and reactivity of biological systems at an atomistic level. Manganese Superoxide Dismutase (MnSOD) is an essential mitochondrial antioxidant enzyme that protects organisms against oxidative damage, dismutating superoxide radical into H2O2 and O2. The active site of the protein presents a Mn ion in a distorted trigonal?bipyramidal environment, coordinated by H26, H74, H163, D159 and one OH- ion or H2O molecule. The catalytic cycle of the enzyme is a ping-pong mechanism involving Mn3+/Mn2+. It is known that nitration of Y34 is responsible for enzyme inactivation. In this work by using computer simulation tools we suggest that Y34 nitration affect protein function by restricting ligand access to the active site. On the other hand, in order to understand the preference for the nitration of Y34, we have studied the mechanism of tyrosine nitration by peroxynitrite by means of hybrid quantum mechanics-molecular mechanics (QM-MM).