Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:6.2.1.1 (ACS)
 78,556 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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 betabeta interface with a water channel also located at that interface. Purified mutant proteins were assayed for Ni/Fe content and examined by electron paramagnetic resonance spectroscopy. Analyses indicate that same metal clusters found in wild-type (WT) ACS/CODH (i.e., the A-, B-, C-, and probably D-clusters) are properly assembled in the mutant enzymes. Stopped-flow kinetics revealed that these centers in the mutants are rapidly reducible by dithionite but are only slowly reducible by CO, suggesting an impaired ability of CO to migrate through the tunnel to the C-cluster. Relative to the WT enzyme, mutant proteins exhibited little CODH or ACS activity (using CO2 as a substrate). Some ACS activity was observed when CO was a substrate, but not the cooperative CO inhibition effect characteristic of WT ACS/CODH. These results suggest that CO and CO2 enter and exit the enzyme at the water channel along the betabeta subunit interface. They also suggest two pathways for CO during synthesis of acetylcoenzyme A, including one in which CO enters the enzyme and migrates through the tunnel before binding at the A-cluster, and another in which CO binds the A-cluster directly from the solvent.
 ...
PMID:Function of the tunnel in acetylcoenzyme A synthase/carbon monoxide dehydrogenase. 1650 6

After activation with NiCl2, the recombinant alpha subunit of the Ni-containing alpha2beta2 acetyl-CoA synthase/carbon monoxide dehydrogenase (ACS/CODH) catalyzes the synthesis of acetyl-CoA from CO, CoA, and a methyl group donated from the corrinoid-iron-sulfur protein (CoFeSP). The alpha subunit has two conformations (open and closed), and contains a novel [Fe4S4]-[Nip Nid] active site in which the proximal Nip ion is labile. Prior to Ni activation, recombinant apo-alpha contain only an Fe4S4 cluster. Ni-activated alpha subunits exhibit catalytic, spectroscopic and heterogeneity properties typical of alpha subunits contained in ACS/CODH. Evidence presented here indicates that apo-alpha is a monomer whereas Ni-treated alpha oligomerizes, forming dimers and higher molecular weight species including tetramers. No oligomerization occurred when apo-alpha was treated with Cu(II), Zn(II), or Co(II) ions, but oligomerization occurred when apo-alpha was treated with Pt(II) and Pd(II) ions. The dimer accepted only 0.5 methyl group/alpha and exhibited, upon treatment with CO and under reducing conditions, the NiFeC EPR signal quantifying to 0.4 spin/alpha. Dimers appear to consist of two types of alpha subunits, including one responsible for catalytic activity and one that provides a structural scaffold. Higher molecular weight species may be similarly constituted. It is concluded that Ni binding to the A-cluster induces a conformational change in the alpha subunit, possibly to the open conformation, that promotes oligomerization. These interrelated events demonstrate previously unrealized connections between (a) the conformation of the alpha subunit; (b) the metal which occupies the proximal/distal sites of the A-cluster; and (c) catalytic activity.
 ...
PMID:Nickel-dependent oligomerization of the alpha subunit of acetyl-coenzyme a synthase/carbon monoxide dehydrogenase. 1788 77

A fascinating feature of some bifunctional enzymes is the presence of an internal channel or tunnel to connect the multiple active sites. A channel can allow for a reaction intermediate generated at one active site to be used as a substrate at a second active site, without the need for the intermediate to leave the safety of the protein matrix. One such bifunctional enzyme is carbon monoxide dehydrogenase/acetyl-CoA synthase from Moorella thermoacetica (mtCODH/ACS). A key player in the global carbon cycle, CODH/ACS uses a Ni-Fe-S center called the C-cluster to reduce carbon dioxide to carbon monoxide and uses a second Ni-Fe-S center, called the A-cluster, to assemble acetyl-CoA from a methyl group, coenzyme A, and C-cluster-generated CO. mtCODH/ACS has been proposed to contain one of the longest enzyme channels (138 A long) to allow for intermolecular CO transport. Here, we report a 2.5 A resolution structure of xenon-pressurized mtCODH/ACS and examine the nature of gaseous cavities within this enzyme. We find that the cavity calculation program CAVENV accurately predicts the channels connecting the C- and A-clusters, with 17 of 19 xenon binding sites within the predicted regions. Using this X-ray data, we analyze the amino acid composition surrounding the 19 Xe sites and consider how the protein fold is utilized to carve out such an impressive interior passageway. Finally, structural comparisons of Xe-pressurized mtCODH/ACS with related enzyme structures allow us to study channel design principles, as well as consider the conformational flexibility of an enzyme that contains a cavity through its center.
 ...
PMID:Xenon in and at the end of the tunnel of bifunctional carbon monoxide dehydrogenase/acetyl-CoA synthase. 1829 27

A general method for isotopic labeling of the purine base moiety of nucleotides and RNA has been developed through biochemical pathway engineering in vitro. A synthetic scheme was designed and implemented utilizing recombinant enzymes from the pentose phosphate and de novo purine synthesis pathways, with regeneration of folate, aspartate, glutamine, ATP, and NADPH cofactors, in a single-pot reaction. Syntheses proceeded quickly and efficiently in comparison to chemical methods with isolated yields up to 66% for 13C-, 15N-enriched ATP and GTP. The scheme is robust and flexible, requiring only serine, NH4+, glucose, and CO2 as stoichiometric precursors in labeled form. Using this approach, U-13C- GTP, U-13C, 15N- GTP, 13C 2,8- ATP, and U-15N- GTP were synthesized on a millimole scale, and the utility of the isotope labeling is illustrated in NMR spectra of HIV-2 transactivation region RNA containing 13C 2,8-adenosine and 15N 1,3,7,9,2-guanosine. Pathway engineering in vitro permits complex synthetic cascades to be effected, expanding the applicability of enzymatic synthesis.
ACS Chem Biol 2008 Aug 15
PMID:Pathway engineered enzymatic de novo purine nucleotide synthesis. 1870 56

Peroxynitrite is formed by the very fast reaction of nitric oxide and superoxide radicals, a reaction that kinetically competes with other routes that chemically consume or physically sequester the reagents. It can behave either as an endogenous cytotoxin toward host tissues or a cytotoxic effector molecule against invading pathogens, depending on the cellular source and pathophysiological setting. Peroxynitrite is in itself very reactive against a few specific targets that range from efficient detoxification systems, such as peroxiredoxins, to reactions eventually leading to enhanced radical formation (e.g., nitrogen dioxide and carbonate radicals), such as the reaction with carbon dioxide. Thus, the chemical biology of peroxynitrite is dictated by the chemical kinetics of its formation and decay and by the diffusion across membranes of the species involved, including peroxynitrite itself. On the other hand, most durable traces of peroxynitrite passing (such as 3-nitrotyrosine) are derived from radicals formed from peroxynitrite by routes that represent extremely low-yield processes but that have potentially critical biological consequences. Here we have reviewed the chemical kinetics of peroxynitrite as a biochemical transient species in order to estimate its rates of formation and decay and then its steady-state concentration in different intra- or extracellular compartments, trying to provide a quantitative basis for its reactivity; additionally, we have considered diffusion across membranes to locate its possible effects. Finally, we have assessed the most successful attempts to intercept peroxynitrite by pharmacological intervention in their potential to increment the existing biological defenses that routinely deal with this cytotoxin.
ACS Chem Biol 2009 Mar 20
PMID:Chemical biology of peroxynitrite: kinetics, diffusion, and radicals. 1926 56

Tin oxide is a unique material of widespread technological applications, particularly in the field of environmental functional materials. New strategies of fractal assessment for tin dioxide thin films formed at different substrate temperatures are of fundamental importance in the development of microdevices, such as gas sensors for the detection of environmental pollutants. Here, tin dioxide thin films with interesting fractal features were successfully prepared by pulsed laser deposition techniques under different substrate temperatures. Fractal method has been first applied to the evaluation of this material. The measurements of carbon monoxide gas sensitivity confirmed that the gas sensing behavior is sensitively dependent on fractal dimensions, fractal densities, and average sizes of the fractal clusters. The random tunneling junction network mechanism was proposed to provide a rational explanation for this gas sensing behavior. The formation process of tin dioxide nanocrystals and fractal clusters could be reasonably described by a novel model.
ACS Nano 2010 Feb 23
PMID:Insight on fractal assessment strategies for tin dioxide thin films. 2008 67

The past several decades have seen a significant rise in atmospheric carbon dioxide levels resulting from the combustion of hydrocarbon fuels. A solar energy based technology to recycle carbon dioxide into readily transportable hydrocarbon fuel (i.e., a solar fuel) would help reduce atmospheric CO2 levels and partly fulfill energy demands within the present hydrocarbon based fuel infrastructure. We review the present status of carbon dioxide conversion techniques, with particular attention to a recently developed photocatalytic process to convert carbon dioxide and water vapor into hydrocarbon fuels using sunlight.
ACS Nano 2010 Mar 23
PMID:Toward solar fuels: photocatalytic conversion of carbon dioxide to hydrocarbons. 2014 Nov 75

Pd/Au bimetallic alloys catalyze many important reactions ranging from the synthesis of vinyl acetate and hydrogen peroxide to the oxidation of carbon monoxide and trimerization of acetylene. It is known that the atomic-scale geometry of these alloys can dramatically affect both their reactivity and selectivity. However, there is a distinct lack of experimental characterization and quantification of ligand and ensemble effects in this system. Low-temperature, ultrahigh vacuum scanning tunneling microscopy is used to investigate the atomic-scale geometry of Pd/Au111 near-surface alloys and to spectroscopically probe their local electronic structure. The results reveal that the herringbone reconstruction of Au111 provides entry sites for the incorporation of Pd atoms in the Au surface and that the degree of mixing is dictated by the surface temperature. At catalytically relevant temperatures the distribution of low coverages of Pd in the alloy is random, except for a lack of nearest neighbor pairs in both the surface and subsurface sites. Scanning tunneling spectroscopy is used to examine the electronic structure of the individual Pd atoms in surface and subsurface sites. This work reveals that in both surface and subsurface locations, Pd atoms display a very similar electronic structure to the surrounding Au atoms. However, individual surface and subsurface Pd atoms are depleted of charge in a very narrow region at the band edge of the Au surface state. dI/dV images of the phenomena demonstrate the spatial extent of this electronic perturbation.
ACS Nano 2010 Mar 23
PMID:Atomic-scale geometry and electronic structure of catalytically important pd/au alloys. 2014 38

A powerful means of enhancing our understanding of the structures and functions of enzymes that contain nickel-sulfur bonds, such as Ni superoxide dismutase, acetyl-coenzyme A synthase/carbon monoxide dehydrogenase, [NiFe] hydrogenase, and methyl-CoM reductase, involves the investigation of model compounds with similar structural and/or electronic properties. In this study, we have characterized a trans-mu-1,2-disulfido-bridged dinickel(II) species, [{(tmc)Ni}(2)(S(2))](2+) (1, tmc = 1,4,8,11-tetramethyl-1,4,8,11-tetraazacyclotetradecane) by using electronic absorption, magnetic circular dichroism (MCD), and resonance Raman (rR) spectroscopic techniques, as well as density functional theory (DFT) and time-dependent DFT computational methods. Our computational results, validated on the basis of the experimental MCD data and previously reported (1)H NMR spectra, reveal that 1 is best described as containing two antiferromagnetically coupled high-spin Ni(II) centers. A normal coordinate analysis of the rR vibrational data was performed to quantify the core bond strengths, yielding force constants of k(Ni-S) = 2.69 mdyn/A and k(S-S) = 2.40 mdyn/A. These values provide a useful basis for a comparison of metal-S/O bonding in 1 and related Ni(2)(O(2)), Cu(2)(O(2)), and Cu(2)(S(2)) dimers. In both the disulfido and the peroxo species, the lower effective nuclear charge of Ni(II) as compared to Cu(II) results in a decreased covalency, and thus relatively weaker metal-S/O bonding interactions in the Ni(2) dimers than in the Cu(2) complexes.
 ...
PMID:Spectroscopic and computational studies of a trans-mu-1,2-disulfido-bridged dinickel species, [{(tmc)Ni}(2)(S(2))](OTf)(2): comparison of end-on disulfido and peroxo bonding in (Ni(II))(2) and (Cu(II))(2) species. 2019 95

Poly(propylene carbonate) (PPC), a polymer produced from CO2, has been melt-mixed with 30 wt % poly(methyl methacrylate) (PMMA) with the aim of enhancing the physical properties of PPC for practical use but keeping a relatively high CO2 fixing rate in the compound. The observation of a coarse phase structure with a large PMMA domain size and a large size distribution in the blend indicates the immiscibility between PPC and PMMA. The addition of a small amount of poly(vinyl acetate) (PVAc) not only shifts the glass transition temperatures (T(g)'s) of both PPC and PMMA markedly but also significantly increases the modulus and tensile strength of the blend. The prepared compound with 5 per hundred parts of resin PVAc shows a 26 times higher elastic modulus and an approximately 3.8 times higher tensile strength than pure PPC at room temperature. The morphological investigation indicates that the incorporation to PVAC not only induces the finer dispersion of PMMA in the PPC matrix but also results in the phase transformation from a sea-island to a co-continuous structure.
ACS Appl Mater Interfaces 2009 Aug
PMID:Compatibilization by homopolymer: significant improvements in the modulus and tensile strength of PPC/PMMA blends by the addition of a small amount of PVAc. 2035 79


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>