Title: Redox, haem and CO in enzymatic catalysis and regulation.

Authors: Ragsdale, Stephen W; Yi, Li; Bender, Güneş; Gupta, Nirupama; Kung, Yan; Yan, Lifen; Stich, Troy A; Doukov, Tzanko; Leichert, Lars; Jenkins, Paul M; Bianchetti, Christopher M; George, Simon J; Cramer, Stephen P; Britt, R David; Jakob, Ursula; Martens, Jeffrey R; Phillips Jr, George N; Drennan, Catherine L

Published In Biochem Soc Trans, (2012 Jun 01)

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.

PubMed ID: 22616859

MeSH Terms: No MeSH terms associated with this publication