The Roles of Thiolate-Heme Proteins,Other Than the P450 Cytochromes,in the Regulation of Heme-Sensor Proteins

摘要

Cytochrome P450,nitric oxide synthase,and chloroperoxidase are typical thiolate-heme enzymes,in which heme iron coordinated with the cysteine thiolate activates molecular oxygen or hydrogen peroxide.A new group of thiolate-heme proteins is becoming recognized.In these proteins,termed heme-responsive/sensing proteins,or simply heme-sensor proteins,the thiolate-heme iron has a sensor function.All known heme-sensor proteins use a cysteine residue to bind heme.The first question is why cysteine is employed in this capacity.Ligation of heme with thiolate,the presence of re-dox-dependent ligand switches,fast heme dissociation rates from the heme-sensor proteins,and formation of 5-coordi-nated NO-Fe(II)heme complexes,appear to be common characteristics of heme-sensor proteins.The Cys-Pro(CP)motif may also be important for heme binding in some heme-sensor proteins.In this minireview,we summarize the inorganic and physicochemical characters of heme-sensor proteins,and include short comments on heme-regulated inhibitor(HRI),and neuronal PAS protein 2(NPAS2),under study in our laboratory over the last several years.Some gas-sensing heme-sensor proteins,with thiolate-heme complexes,will also be briefly discussed.