title: Essential Amino Acid Residues Controlling the Unique Regioselectivity of Heme Oxygenase in Pseudomonas aeruginosa.
abstract: Heme oxygenase (HO), an amphipathic microsomal protein, catalyzes the oxygen-dependent degradation of heme (iron-protoporphyrinIX) to alpha-biliverdin, CO, and free iron ion. Interestingly, all of HO regiospecifically oxidize the alpha-meso position of the heme to form alpha-biliverdin isomer while nonenzymatic heme degradation forms all four possible alpha-, beta-, gamma-, delta-biliverdin isomers at nearly identical yield. Recently, an interesting example has been found in HO (PigA) of the Gram-negative bacterium Pseudomonas aeruginosa, which does not produce alpha-biliverdin at all, but forms the mixture of beta- and gamma-biliverdins at a ratio of 3:7. While studying the mechanism of the unique regioselectivty of PigA, we found essential amino acid residues, Lys34, Lys132, and Phe189, controlling the unique regioselectivity of PigA. In this communication, we show that Lys34 and Lys132 are essential amino acid residues to hold the rotated heme in the active site of PigA via hydrogen-bonding interaction with the heme propionate and that Phe189 controls the product ratio of beta- and delta-biliverdins via steric interaction with heme substituents. These interactions place the beta- or delta-meso position of the heme at the oxidation site of PigA, leading to the unique regioselectivity.
authors.affiliation: Institute for Molecular Science and Center for Integrative Bioscience, Okazaki National Research Institutes, Myodaiji, Okazaki 444-8585, Japan. hiro@ims.ac.jp
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Fujii
authors.forename: Xuhong
authors.initials: X
authors.lastname: Zhang
authors.forename: Tadashi
authors.initials: T
authors.lastname: Yoshida
mesh_terms: D000409:Alanine / Q000737:chemistry / Q000378:metabolism; D001665:Binding Sites; D006419:Heme Oxygenase (Decyclizing) / Q000737:chemistry* / Q000378:metabolism*; D006860:Hydrogen Bonding; D008239:Lysine / Q000737:chemistry / Q000378:metabolism; D008958:Models, Molecular; D011550:Pseudomonas aeruginosa / Q000201:enzymology*; D013329:Structure-Activity Relationship
chemical_list: D006419:Heme Oxygenase (Decyclizing); D008239:Lysine; D000409:Alanine