Function of the tunnel in acetylcoenzyme A synthase/carbon monoxide dehydrogenase

@article{Tan2006FunctionOT,
  title={Function of the tunnel in acetylcoenzyme A synthase/carbon monoxide dehydrogenase},
  author={Xiangshi Tan and Anne Volbeda and Juan C. Fontecilla-Camps and Paul A. Lindahl},
  journal={JBIC Journal of Biological Inorganic Chemistry},
  year={2006},
  volume={11},
  pages={371-378}
}
Acetylcoenzyme A synthase/carbon monoxide dehydrogenase (ACS/CODH) contains two Ni–Fe–S active-site clusters (called A and C) connected by a tunnel through which CO and CO2 migrate. Site-directed mutants A578C, L215F, and A219F were designed to block the tunnel at different points along the region between the two C-clusters. Two other mutant proteins F70W and N101Q were designed to block the region that connects the tunnel at the ββ interface with a water channel also located at that interface… 
CO Dehydrogenase/Acetyl‐CoA Synthase
TLDR
The bifunctional tetrameric enzyme carbon monoxide dehydrogenase (CODH)/acetyl-CoA synthase (ACS) undergoes a conformational change that blocks the tunnel near the active site, preventing the escape of the toxic CO from within the enzyme upon methyl binding to nickel.
Tunnel mutagenesis and Ni-dependent reduction and methylation of the α subunit of acetyl coenzyme A synthase/carbon monoxide dehydrogenase
Two isolated α subunit mutants (A110C and A222L) of the α2β2 acetyl coenzyme A synthase (ACS)/carbon monoxide dehydrogenase (CODH) from Moorella thermoacetica were designed to block the CO-migrating
Xenon in and at the end of the tunnel of bifunctional carbon monoxide dehydrogenase/acetyl-CoA synthase.
TLDR
A 2.5 A resolution structure of xenon-pressurized mtCODH/ACS is reported and the nature of gaseous cavities within this enzyme are examined to study channel design principles, as well as consider the conformational flexibility of an enzyme that contains a cavity through its center.
Metalloproteins/metalloenzymes for the synthesis of acetyl-CoA in the Wood-Ljungdahl pathway
This paper focuses on the group of metalloproteins/metalloenzymes in the acetyl-coenzyme A synthesis pathway of anaerobic microbes called Wood-Ljungdahl pathway, including formate dehydrogenase
A substrate channel in the nitrogenase MoFe protein
TLDR
Results are consistent with the water-filled channel functioning as a substrate channel in the MoFe protein, given that each of the amino acids that were substituted is remote from the active site.
The quest for a functional substrate access tunnel in FeFe hydrogenase.
TLDR
This work reviews the literature on gas channels in proteins and enzymes and reports on the use of site-directed mutagenesis and various kinetic methods, which proved useful for characterizing substrate access to the active site of NiFe hydrogenase, to test the putative "static" H2 channel of FeFe hydrogenases.
Carbamate transport in carbamoyl phosphate synthetase: a theoretical and experimental investigation.
TLDR
The transport of carbamate through the large subunit of carbamoyl phosphate synthetase (CPS) from Escherichia coli was investigated by molecular dynamics and site-directed mutagenesis, finding that the tunnel is composed of three continuous water pockets and two narrow connecting parts, near Ala-23 and Gly-575.
The binding and release of oxygen and hydrogen peroxide are directed by a hydrophobic tunnel in cholesterol oxidase.
TLDR
The steady-state kinetics of both wild-type and tunnel mutant enzymes are consistent with formation of a ternary complex of steroid and oxygen during catalysis, and kinetic cooperativity with respect to molecular oxygen is observed with the tunnel mutants, but not with the wild- type enzyme.
Redox potentials and protonation of the A-cluster from acetyl-CoA synthase. A density functional theory study.
TLDR
The mechanism of PCET reductive activation of the A-cluster has been proposed for the methylation catalytic step of acetyl-CoA synthase enzyme.
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References

SHOWING 1-10 OF 34 REFERENCES
The metalloclusters of carbon monoxide dehydrogenase/acetyl-CoA synthase: a story in pictures
TLDR
Recent studies have revealed Ni-Ni to be the active state, unveiled the source of the heterogeneity that had plagued studies of CODH/ACS for decades, and produced a metal-replacement strategy to generate highly active and nearly homogeneous enzyme.
Acetyl-coenzyme A synthase: the case for a Nip0-based mechanism of catalysis
  • P. Lindahl
  • Chemistry
    JBIC Journal of Biological Inorganic Chemistry
  • 2004
TLDR
In this review, evidence is presented that Nip achieves a zero-valent state at low potentials and during catalysis, and Ni-organometallic complexes in which the Ni exhibits analogous reactivity properties when reduced to the zero-Valent state are reinforced.
Genetic construction of truncated and chimeric metalloproteins derived from the alpha subunit of acetyl-CoA synthase from Clostridium thermoaceticum.
TLDR
The proposed chimeric proteins exhibited EPR signals that were not the simple sum of the signals from the separate proteins, suggesting magnetic interactions between clusters and the potential for using genetics to simplify the study of complex multicentered metalloenzymes.
The tunnel of acetyl-coenzyme a synthase/carbon monoxide dehydrogenase regulates delivery of CO to the active site.
TLDR
NiFeC EPR intensity of alpha developed in accordance with an apparent K(d) = 30 microM, suggesting that the state exhibiting this signal is not responsible for inhibiting catalysis or methyl group transfer and that it may be a catalytic intermediate.
Crystallographic evidence for a CO/CO2 tunnel gating mechanism in the bifunctional carbon monoxide dehydrogenase/acetyl coenzyme A synthase from Moorella thermoacetica
TLDR
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 CO2/CO tunnel gating mechanism.
A Ni-Fe-Cu Center in a Bifunctional Carbon Monoxide Dehydrogenase/ Acetyl-CoA Synthase
TLDR
A metallocofactor containing iron, sulfur, copper, and nickel has been discovered in the enzyme carbon monoxide dehydrogenase/acetyl-CoA (coenzyme A) synthase from Moorella thermoacetica and suggests a newly discovered role for copper in biology.
Acetyl coenzyme A synthase: new insights into one of Nature’s bioorganometallic catalysts
  • C. G. Riordan
  • Chemistry, Biology
    JBIC Journal of Biological Inorganic Chemistry
  • 2004
TLDR
The redox reactions promoted by COdH and ACS are reminiscent of the industrial water-gas shift and Monsanto acetic acid synthesis reactions, respectively, that may serve to connect the biological and organometallic communities while expanding the bioorganometallic paradigm beyond B12 chemistry.
Evidence of a Molecular Tunnel Connecting the Active Sites for CO2 Reduction and Acetyl-CoA Synthesis in Acetyl-CoA Synthase from Clostridium thermoaceticum
Autotrophic bacteria and archaea can grow on CO2 and H2 as their only source of carbon and energy.1 The central enzyme responsible for this process is acetyl-CoA synthase (ACS). ACS from Clostridium
Effect of Zn on acetyl coenzyme a synthase: evidence for a conformational change in the alpha subunit during catalysis.
TLDR
This is the first evidence that the structurally-characterized conformations of the alpha subunit change during catalysis, indicating a mechanistic role for this conformational change.
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