Density functional study on geometry and electronic structure of nitrile hydratase active site model

Abstract

AbstractNitrile Hydratase (R. Sp. 771, NHase, EC. 4.2.1.84, CAS registration no. 82391‐37‐5), the enzyme that plays an important role in the industrial production of acrylamide, is studied theoretically in this article. For the first time the electronic structure of the active site of nitrosylated form with a proper oxidation state of the cysteine ligands is calculated using the density functional theory (DFT) method with the Becke, Lee, Yang, and Paar (B3LYP)6‐31G* functional. The optimized geometries of six and five coordinated complexes are different, showing that the photodissociation of NO triggers a substantial relaxation of the NHase active site. The major structural change is a shift of the position of iron with respect to the four equatorial ligands, which resembles a heme doming observed in myoglobins. Calculated charge distribution supports the role of Fe as a possible Lewis acid in catalytic cycle. We found that the cysteine‐sulfinic residue (Cys112) is very strongly polarized in NHase. Sulfur atom Sγ Cys112 is predicted to be the most positively charged center. This result gives independent support to a very recent finding of the critical role of an oxidation in the position Cys112 for preserving catalytic activity of the enzyme (Endo, I.; Nojiri, M.; Tsujimura, M.; Nakasako, M.; Nagashima, S.; Yohda, M.; Odaka, M. J Inorgan Biochem 2001, 83, 247). © 2002 Wiley Periodicals, Inc. Int J Quantum Chem, 2002