The Roles of Thiolate-Heme Proteins, Other Than the P450 Cytochromes, in the Regulation of Heme-Sensor Proteins
Abstract
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 redox-dependent ligand switches, fast heme dissociation rates from the heme-sensor proteins, and formation of 5-coordinated 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.