title: Reversible heme-dependent regulation of human cystathionine β-synthase by a flavoprotein oxidoreductase.
abstract: Human CBS is a PLP-dependent enzyme that clears homocysteine, gates the flow of sulfur into glutathione, and contributes to the biogenesis of H(2)S. The presence of a heme cofactor in CBS is enigmatic, and its conversion from the ferric- to ferrous-CO state inhibits enzyme activity. The low heme redox potential (-350 mV) has raised questions about the feasibility of the ferrous-CO state forming under physiological conditions. Herein, we provide the first evidence of reversible inhibition of CBS by CO in the presence of a human flavoprotein and NADPH. These data provide a mechanism for cross talk between two gas-signaling systems, CO and H(2)S, via heme-mediated allosteric regulation of CBS.
authors.affiliation: Department of Biological Chemistry, University of Michigan Medical Center, Ann Arbor, Michigan 48109-0600, United States.
authors.forename: Omer
authors.initials: O
authors.lastname: Kabil
authors.forename: Colin L
authors.initials: CL
authors.lastname: Weeks
authors.forename: Sebastián
authors.initials: S
authors.lastname: Carballal
authors.forename: Carmen
authors.initials: C
authors.lastname: Gherasim
authors.forename: Beatriz
authors.initials: B
authors.lastname: Alvarez
authors.forename: Thomas G
authors.initials: TG
authors.lastname: Spiro
authors.forename: Ruma
authors.initials: R
authors.lastname: Banerjee
mesh_terms: D000494:Allosteric Regulation; D002248:Carbon Monoxide / Q000378:metabolism*; D003541:Cystathionine beta-Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D005290:Ferric Compounds / Q000378:metabolism; D005296:Ferrous Compounds / Q000378:metabolism; D005420:Flavoproteins; D006418:Heme / Q000378:metabolism*; D006801:Humans; D006862:Hydrogen Sulfide / Q000378:metabolism*; D010084:Oxidation-Reduction; D010088:Oxidoreductases / Q000378:metabolism*
chemical_list: D005290:Ferric Compounds; D005296:Ferrous Compounds; D005420:Flavoproteins; D006418:Heme; D002248:Carbon Monoxide; D010088:Oxidoreductases; D003541:Cystathionine beta-Synthase; D006862:Hydrogen Sulfide