Molecular dynamics study of the active site of Methylamine Dehydrogenase

GUSTAVO PIERDOMINICI-SOTTILE; JULIÁN ECHAVE; JULIANA PALMA

JOURNAL OF PHYSICAL CHEMISTRY B

ACS Publications

Año: 2006 vol. 110 p. 11592 - 11599

1089-5647

We have obtained AMBER94 force field parameters for the TTQ cofactor of the enzyme Methylamine Dehydrogenase (MADH). This enzyme catalyzes the oxidation of methylamine to produce formaldehyde and ammonia. In the rate-determinant step of the catalized reaction a proton is transferred from the methyl group of the substrate to residue Asp76. We used the new parameters to perform molecular dynamics simulations of MADH in order to characterize the dynamics of the active site prior to the proton transfer step. We found that only one of the oxygen atoms of Asp76 can act as acceptor of the proton. The other oxygen interacts with Thr122 via a strong hydrogen bond. In contrast, because of the rotation the methyl group of the substrate, the three methyl hydrogen atoms are alternatively in position to be transferred. The distance that the proton has to travel presents a broad distribution with a peak at 1.0Å and reaches values as short as 0.8 Å. The fluctuations of the distance between the donor and the acceptor of the proton have their main frequency components below 50cm-1. No significant frequency components appear above 250cm-1.