title: Redox, haem and CO in enzymatic catalysis and regulation.
abstract: The present paper describes general principles of redox catalysis and redox regulation in two diverse systems. The first is microbial metabolism of CO by the Wood-Ljungdahl pathway, which involves the conversion of CO or H2/CO2 into acetyl-CoA, which then serves as a source of ATP and cell carbon. The focus is on two enzymes that make and utilize CO, CODH (carbon monoxide dehydrogenase) and ACS (acetyl-CoA synthase). In this pathway, CODH converts CO2 into CO and ACS generates acetyl-CoA in a reaction involving Ni·CO, methyl-Ni and acetyl-Ni as catalytic intermediates. A 70 Å (1 Å=0.1 nm) channel guides CO, generated at the active site of CODH, to a CO 'cage' near the ACS active site to sequester this reactive species and assure its rapid availability to participate in a kinetically coupled reaction with an unstable Ni(I) state that was recently trapped by photolytic, rapid kinetic and spectroscopic studies. The present paper also describes studies of two haem-regulated systems that involve a principle of metabolic regulation interlinking redox, haem and CO. Recent studies with HO2 (haem oxygenase-2), a K+ ion channel (the BK channel) and a nuclear receptor (Rev-Erb) demonstrate that this mode of regulation involves a thiol-disulfide redox switch that regulates haem binding and that gas signalling molecules (CO and NO) modulate the effect of haem.
authors.affiliation: Department of Biological Chemistry, University of Michigan, Ann Arbor, MI 48109, U.S.A. sragsdal@umich.edu
authors.forename: Stephen W
authors.initials: SW
authors.lastname: Ragsdale
authors.forename: Li
authors.initials: L
authors.lastname: Yi
authors.forename: Güneş
authors.initials: G
authors.lastname: Bender
authors.forename: Nirupama
authors.initials: N
authors.lastname: Gupta
authors.forename: Yan
authors.initials: Y
authors.lastname: Kung
authors.forename: Lifen
authors.initials: L
authors.lastname: Yan
authors.forename: Troy A
authors.initials: TA
authors.lastname: Stich
authors.forename: Tzanko
authors.initials: T
authors.lastname: Doukov
authors.forename: Lars
authors.initials: L
authors.lastname: Leichert
authors.forename: Paul M
authors.initials: PM
authors.lastname: Jenkins
authors.forename: Christopher M
authors.initials: CM
authors.lastname: Bianchetti
authors.forename: Simon J
authors.initials: SJ
authors.lastname: George
authors.forename: Stephen P
authors.initials: SP
authors.lastname: Cramer
authors.forename: R David
authors.initials: RD
authors.lastname: Britt
authors.forename: Ursula
authors.initials: U
authors.lastname: Jakob
authors.forename: Jeffrey R
authors.initials: JR
authors.lastname: Martens
authors.forename: George N
authors.initials: GN
authors.lastname: Phillips
authors.forename: Catherine L
authors.initials: CL
authors.lastname: Drennan
mesh_terms: D000106:Acetate-CoA Ligase / Q000378:metabolism*; D000445:Aldehyde Oxidoreductases / Q000378:metabolism*; D000818:Animals; D055162:Biocatalysis; D002248:Carbon Monoxide / Q000378:metabolism*; D006418:Heme / Q000378:metabolism*; D006801:Humans; D009097:Multienzyme Complexes / Q000378:metabolism*; D010084:Oxidation-Reduction
chemical_list: D009097:Multienzyme Complexes; D006418:Heme; D002248:Carbon Monoxide; D000445:Aldehyde Oxidoreductases; C019823:carbon monoxide dehydrogenase; D000106:Acetate-CoA Ligase