Acetyl Coenzyme A synthase ACS

ACS are present in methanogens, acetogens and carboxydotrophic microorganisms where they catalyze the synthesis and/or the decarbonylation of acetylCoA according to the following reaction, where CoFeS correspond to a correnoid/cobalt containing iron-sulfur protein [158, 165]. 

For Lindahl et al. [177] Ni(I)-CO is not a catalyticaUy competent intermediate there is no example of Ni(I) that supports methylation and forms Ni(III)-CH3. Lindahl et al. did not observe reduction of either the B or C-cluster of CODH during methylation, so instead of invoking CODH/ACS inter-electron transfer, they proposed a D-site , possibly a pair of cysteine thiolates, to provide the two electrons required for the oxidative methylation [177]. 

A major breakthrough in the field was the publication of the three-dimensional structure of M. thermoacetica CODH/ACS by Drennan et al. [156]. As it is often the case with crystal structures, the active site was surprising in more than one 

The crystallographic restrlts, that support the existence of a gating mechanism for CO diffusion from the C-cluster, where it is synthesized, to the A-cluster, can be used to re-interpret several previously reported hypotheses. For instance, lindahl et al. proposed that the C and A-clusters, known to be magnetically isolated, were nevertheless coupled through conformational changes [184]. This can now be understood in terms of C-duster-synthesized CO accessibility to the A-duster. The proposed reductase (CO synthesis) and synthase (acetyl-CoA synthesis) modes for CODH/ACS were based on the observation that when the CO2 reduction was carried out in the absence of substrates for acetyl-CoA synthesis, CO production from CO2 and reductant had lower k j and higher than when those substrates 

Many microorganisms are capable of using hydrogen as a source of reducing power or protons as final acceptors according to the following reaction. 

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Carbon Monoxide Dehydrogenase (COdH) and Acetyl Coenzyme A Synthase (ACS)... 

Fig.4 A Active site of acetyl coenzyme A synthase (ACS). B Active site of Ni-superoxide dismutase (Ni SOD)...

Acetyl coenzyme A synthase of C. thermoaceticum has a (aP)2 dimer-of-dimers structure with subunit molecular masses 78 kDa (a) and 71 kDa (P). Analysis indicated 12 Fe, 14 S, 2 Ni, 1 Zn per ap dimer. CO dehydrogenase activity resides in the P subunit (AcsA). This subunit has 46% identity (75% homology) with the R. rubrum C00S protein and appears to contain cluster C. Cluster A is located at least partially in the a subunit (AcsA) ACS of Methanosarcina barkeri comprises five subunits a, 84-93 kDa P, 63 kDa y, 53 kDa 8, 51 kDa , 20 kDa [141], The CODH activity is associated with the a subunit. 

Carbon Monoxide Dehydrogenase/acetyl Coenzyme A Synthase (CODH/ACS) 7... 

CARBON MONOXIDE DEHYDROGENASE/ ACETYL COENZYME A SYNTHASE (CODH/ACS)... 

Carbon monoxide dehydrogenase/acetyl coenzyme A synthase (CODH/ACS) describes two different classes of enzymes carbon monoxide dehydrogenase (CODH) isolated from Rhodospirillum rubrum or Carboxydothermus hydrogenoformans reversibly oxidizes CO to CO2 according to equation (2), and the bifunctional CODH/ACS enzyme from Moorella thermoacetica catalyzes the reversible reduction of CO2 to CO (CODH) and acetyl coenzyme assembly/disassembly (ACS) (equation 3). ... 

Fig. 3 Structure of the carbon monoxide dehydrogenase/acetyl coenzyme A synthase (CODH/ACS) hetero-tetramer. A Polypeptide fold of the CODH dimer (center) and of ACS in the closed (left) and open subunit conformation (right). Metal sites and inorganic sul-furs are shown as spheres an extensive hydrophobic tunnel network is highlighted in dark grey. B Zoomed depiction of the CODH active site. Dashed lines indicate putative H-bonds...

The bacterial metalloenzyme acetyl coenzyme A synthase/CO dehydrogenase (ACS/CODH) catalyzes two very important biological processes, namely the reduction of atmospheric CO2 to CO and the synthesis of acetyl coerrzyme A from CO, a methyl from a methylated corrinoid iron-sulfur protein, and the thiol coenzyme A [166-168]. This bifunctional errzyme is the key to the Wood-Ljiungahl pathway of anaerobic CO2 fixation (Scheme 1.18) and a major component of the global carbon cycle. Reactions catalyzed by CODH and ACS are shown in Eqs. (1.4) and (1.5) below. 

Figure 3. The acetyl coenzyme-A pathway as employed by the acetogens which produces both biochemical components and some energy in the form of adenosine triphosphate (ATP) (22). The acetogens are assumed here to have been the first microbes. Note that hydrothermal formic acid can feed into the Eastern branch (36) of the cycle via tetrahydrofolate (H4polate) in prokaryotes, ahead of carbon dioxide, by disproportionation to CO2 and H2. Carbon monoxide dehydrogenase/acetyl coenzyme-A synthase (CODH/ACS) is the bifunctional enzyme wherein one nickel is involved in the reduction of CO2 (in the Western branch ) and another nickel is involved in synthesizing the...

Fig. 11. Active sites and reactions of the bifunctional CODH/ACS. For synthesis of acetyl-CoA, two electrons are transferred from external electron donors to Cluster B of the CODH subunit. Electrons are relayed to Cluster C which reduces CO2 to CO. The CO is proposed to be channeled to Cluster A of the ACS subunit to form a metal-CO adduct that combines with the methyl group of the CFeSP and CoA to form acetyl-CoA. For utilization of acetyl-CoA, these reactions are reversed. The abbreviations are CODH, CO dehydrogenase ACS, acetyl-CoA synthase CFeSP, the corrinoid iron-sulfur protein CoA, Coenzyme A.

Fig. 7. Enzyme-coupled assay in which the hydrolase-catalyzed reaction releases acetic acid. The latter is converted by acetyl-CoA synthetase (ACS) into acetyl-CoA in the presence of (ATP) and coenzyme A (CoA). Citrate synthase (CS) catalyzes the reaction between acetyl-CoA and oxaloacetate to give citrate. The oxaloacetate required for this reaction is formed from L-malate and NAD in the presence of L-malate dehydrogenase (l-MDH). Initial rates of acetic acid formation can thus be determined by the increase in adsorption at 340 nm due to the increase in NADH concentration. Use of optically pure (Ry- or (5)-acetates allows the determination of the apparent enantioselectivity i app i81)-...

The nickel enzymes covered in this article can be divided into two groups redox enzymes and hydrolases. The five Ni redox enzymes are hydrogenase, CO dehydrogenase (CODH), acetyl-CoA synthase (ACS), methyl-Coenzyme M reductase (MCR), and superoxide dismutase (SOD). Glyoxalase-I and urease are Ni hydrolases. Ni proteins that are not enzymes are not covered, because they have been recently reviewed. These include regulatory proteins (NikR) and chaperonins and metal uptake proteins (CooJ, CooE, UreE, and ABC transporters). A recent crystal structure of NikR, shown in Figure l(i), is a notable recent achievement in this area. ... 

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