Cytochrome P450 was the first hemoprotein found to have a thiolate anion as the axial ligand of the heme. Several other heme-thiolate proteins, including nitric oxide synthase, were later found in animals, plants, and microorganisms. Both cytochrome P450 and nitric oxide synthase, two major members of the heme-thiolate protein family, catalyze monooxygenase reactions, but the physiological functions of other heme-thiolate proteins are apparently highly diverse. Chloroperoxidase of a mold, Caldaryomyces fumago, catalyzes a haloperoxidase reaction. CooA of a bacterium, Rhodospirillum rubrum, and heme-regulated eIF2 alpha kinase of animals function as the sensors for carbon monoxide and nitric oxide, respectively, to elicit biological responses to these gases. The role of heme in the enzymatic activity of cystathionine beta-synthase is still unknown. It is likely that more heme-thiolate proteins with diversified functions will be found in various organisms in the future. (c) 2005 Elsevier Inc. All rights reserved.