Crystallographic evidence for a CO/CO(2) tunnel gating mechanism in the bifunctional carbon monoxide dehydrogenase/acetyl coenzyme A synthase from Moorella thermoacetica.
Acetyl coenzyme A synthase (ACS) acts in concert with carbon monoxide dehydrogenase (CODH) to catalyze the formation of acetyl-coenzyme A from CO(2)-derived CO and CH(3)(+) molecules. Recent crystal structures have shown that the three globular domains constituting the ACS subunit may be arranged in either a closed or an open conformation. A long hydrophobic tunnel network allows diffusion of CO between the CODH and the ACS active sites in the closed form, but it is blocked in the open form. On the other hand, the active site of ACS is only accessible for coenzyme A and the methyl donating protein in the open domain conformation. Although several metal compositions have been observed for this active site, present consensus is that it consists of a Ni-Ni-[Fe(4)S(4)] cluster. The observed conformational changes of ACS and the resulting different substrate accessibilities of the catalytic central nickel are reviewed here in the context of a putative CO(2)/CO tunnel gating mechanism.
Volbeda
Anne
A
Laboratoire de Cristallographie et de Cristallogenèse des Protéines, Institut de Biologie Structurale J.P. Ebel, 41 rue Jules Horowitz, 38027 Cédex 1, Grenoble, France.
Fontecilla-Camps
Juan C
JC
D000105:Acetyl Coenzyme A / Q000737:chemistry* / Q000378:metabolism; D000445:Aldehyde Oxidoreductases / Q000737:chemistry* / Q000378:metabolism; D001665:Binding Sites; D002245:Carbon Dioxide / Q000737:chemistry*; D002248:Carbon Monoxide / Q000737:chemistry*; D002384:Catalysis; D003013:Clostridium / Q000201:enzymology*; D018360:Crystallography, X-Ray; D057927:Hydrophobic and Hydrophilic Interactions; D007506:Iron-Sulfur Proteins / Q000737:chemistry / Q000378:metabolism; D009097:Multienzyme Complexes / Q000737:chemistry* / Q000378:metabolism; D009532:Nickel / Q000737:chemistry / Q000378:metabolism; D011487:Protein Conformation
D007506:Iron-Sulfur Proteins; D009097:Multienzyme Complexes; D002245:Carbon Dioxide; D000105:Acetyl Coenzyme A; D009532:Nickel; D002248:Carbon Monoxide; D000445:Aldehyde Oxidoreductases; C019823:carbon monoxide dehydrogenase