Environment effects on chemical reactivity of Heme Proteins

D. A. SCHERLIS, M. A. MARTÍ, P. ORDEJON, D. A. ESTRIN

INTERNATIONAL JOURNAL OF QUANTUM CHEMISTRY

Año: 2002 vol. 90 p. 1505 - 1514

0020-7608

Heme proteins are involved in a variety of physiological processes,such as O2 transport, electron transfer, sensing of O2 or CO, and catalysis of redoxreactions. Despite the differences in biologic function, all these proteins have ironprotoporphyrin IX (heme b) as the active site. The amino acids surrounding the activesite are responsible for the specific reactivity of each protein. We analyzed theenvironment effects on binding of small ligands such as O2 and NO to several hemeproteins using density functional theory (DFT) calculations of model systems includingselected amino acid residues, and also DFT calculations of the active site coupled to anelectrostatic representation of the rest of the protein. Specifically, we considered thefollowing problems: (1) the mechanisms underlying inactivation by nitric oxide ofcytochrome P450; (2) O2 affinity of human and Ascaris hemoglobin and the role ofoxygen hydrogen bonding to the distal amino acids; (3) the influence of the amino acidresidues surrounding the proximal histidine in the FeOhistidine bond cleavage uponbinding of NO in FixL, horseradish peroxidase, and human hemoglobin.