Modulation of the NO trans effect in heme proteins: implications for the activation of soluble Guanylate Cyclase.

M. A. MARTÍ, D. A. SCHERLIS, F. A. DOCTOROVICH, P. ORDEJÓN, D. A. ESTRIN.

JOURNAL OF BIOLOGICAL INORGANIC CHEMISTRY

Año: 2003 vol. 5 p. 595 - 600

0949-8257

The binding of NO to the iron heme inguanylate cyclase and other heme proteins induces thecleavage of the proximal histidine bonded to the metal.In this study we assess by means of density functionaltheory (DFT) electronic structure calculations the roleof H-bonding to histidine in the modulation of this effect.We have considered in the first place a model of theisolated active site coordinated with imidazole and imidazolateto mimic the effects of a very strong H-bond.We have also investigated four selected ferrous hemeproteins with different proximal histidine environments:the O2 sensing FixL, horseradish peroxidase C, and the aand b subunits of human hemoglobin. Our results indicatethat polarization and charge transfer effects associatedwith H-bonding to the proximal histidine play afundamental role in the modulation of the NO transeffect in heme proteins. We also find computational evidencesuggesting that protein structural constraints mayaffect significantly the cleavage of the Fe-His bond