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

Acetyl-CoA synthase (ACS identical with ACS/CODH identical with CODH/ACS) from Moorella thermoacetica catalyzes the synthesis of acetyl-CoA from CO, CoA, and a methyl group of a corrinoid-iron-sulfur protein (CoFeSP). A time lag prior to the onset of acetyl-CoA production, varying from 4 to 20 min, was observed in assay solutions lacking the low-potential electron-transfer agent methyl viologen (MV). No lag was observed when MV was included in the assay. The length of the lag depended on the concentrations of CO and ACS, with shorter lags found for higher [ACS] and sub-saturating [CO]. Lag length also depended on CoFeSP. Rate profiles of acetyl-CoA synthesis, including the lag phase, were numerically simulated assuming an autocatalytic mechanism. A similar reaction profile was monitored by UV-vis spectrophotometry, allowing the redox status of the CoFeSP to be evaluated during this process. At early stages in the lag phase, Co(2+)FeSP reduced to Co(+)FeSP, and this was rapidly methylated to afford CH(3)-Co(3+)FeSP. During steady-state synthesis of acetyl-CoA, CoFeSP was predominately in the CH(3)-Co(3+)FeSP state. As the synthesis rate declined and eventually ceased, the Co(+)FeSP state predominated. Three activation reductive reactions may be involved, including reduction of the A- and C-clusters within ACS and the reduction of the cobamide of CoFeSP. The B-, C-, and D-clusters in the beta subunit appear to be electronically isolated from the A-cluster in the connected alpha subunit, consistent with the ~70 A distance separating these clusters, suggesting the need for an in vivo reductant that activates ACS and/or CoFeSP.
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PMID:Autocatalytic activation of acetyl-CoA synthase. 1501 40

Enterobactin (Ent), a prototypic bacterial siderophore, is modified by both the C-glucosyltransferase IroB and the macrolactone hydrolase IroE in pathogenic bacteria that contain the iroA cluster. To investigate the possible effects of glucosylation and macrolactone hydrolysis on the physical properties of Ent, the membrane affinities and iron acquisition rates of Ent and Ent-derived siderophores were measured. The data obtained indicate that Ent has a high membrane affinity (K(x) = 1.5 x 10(4)) similar to that of ferric acinetoferrin, an amphiphile containing two eight-carbon hydrophobic chains. Glucosylation and macrolactone hydrolysis decrease the membrane affinity of Ent by 5-25-fold. Furthermore, in the presence of phospholipid vesicles, the iron acquisition rate is significantly increased by glucosylation and macrolactone hydrolysis, due to the resultant decrease in membrane sequestration of the siderophore. These results suggest that IroB and IroE enhance the ability of Ent-producing pathogens to acquire iron in membrane-rich microenvironments.
ACS Chem Biol 2006 Feb 17
PMID:Enzymatic tailoring of enterobactin alters membrane partitioning and iron acquisition. 1716 37

Soon after a sperm meets an egg, the single fertilized cell splits into two cells, then four, and then eight. Cell division is responsible for producing each of the trillions of cells present in every human body. During adulthood, division supplies replacements for cells lost to age, injury, and disease, but it can also form the basis for illnesses such as cancer. Despite the importance of mitosis in development and medicine, researchers have much to learn about the molecular mechanisms that regulate it. Cell biologist Rebecca Heald of the University of California, Berkeley, is striving to iron out these details. Heald's work concentrates on the mitotic spindle, a structure that is essential for correctly distributing copied chromosomes to daughter cells. Using techniques that blend biology and chemistry, she and her colleagues are identifying molecules and proteins that play major roles in directing this dynamic cell process.
ACS Chem Biol 2006 Oct 24
PMID:Divide and conquer: investigating the mechanisms behind mitosis. 1716 47

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.
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PMID:Nickel-dependent oligomerization of the alpha subunit of acetyl-coenzyme a synthase/carbon monoxide dehydrogenase. 1788 77

Hemoproteins carry out diverse functions utilizing a wide range of chemical reactivity while employing the same heme prosthetic group. It is clear from high-resolution crystal structures and biochemical studies that protein-bound hemes are not planar and adopt diverse conformations. The crystal structure of an H-NOX domain from Thermoanaerobacter tengcongensis (Tt H-NOX) contains the most distorted heme reported to date. In this study, Tt H-NOX was engineered to adopt a flatter heme by mutating proline 115, a conserved residue in the H-NOX family, to alanine. Decreasing heme distortion in Tt H-NOX increases affinity for oxygen and decreases the reduction potential of the heme iron. Additionally, flattening the heme is associated with significant shifts in the N-terminus of the protein. These results show a clear link between the heme conformation and Tt H-NOX structure and demonstrate that heme distortion is an important determinant for maintaining biochemical properties in H-NOX proteins.
ACS Chem Biol 2008 Nov 21
PMID:Probing the function of heme distortion in the H-NOX family. 1903 89

Janus nanoparticles have been synthesized consisting of approximately 5 nm magnetite nanoparticles coated on one side with a pH-dependent and temperature-independent polymer (poly(acrylic acid), PAA), and functionalized on the other side by a second (tail) polymer that is either a pH-independent polymer (polystyrene sodium sulfonate, PSSNa) or a temperature-dependent polymer (poly(N-isopropyl acrylamide), PNIPAM). These Janus nanoparticles are dispersed stably as individual particles at high pH values and low temperatures, but can self-assemble at low pH values (PSSNa) or at high temperatures (>31 degrees C) (PNIPAM) to form stable dispersions of clusters of approximately 80-100 nm in hydrodynamic diameter. The Janus nanoparticle compositions were verified using FTIR and XPS, and their structures observed directly by TEM. Their clustering behavior is analyzed by dynamic light scattering and zeta potential measurements.
ACS Nano 2008 Sep 23
PMID:Reversible clustering of pH- and temperature-responsive Janus magnetic nanoparticles. 1920 18

In this study, we report a rapid sonochemical synthesis of monodisperse nonaggregated Fe(3)O(4)@SiO(2) magnetic nanoparticles (NPs). We found that coprecipitation of Fe(II) and Fe(III) in aqueous solutions under the effect of power ultrasound yields smaller Fe(3)O(4) NPs with a narrow size distribution (4-8 nm) compared to the silent reaction. Moreover, the coating of Fe(3)O(4) NPs with silica using an alkaline hydrolysis of tetraethyl orthosilicate in ethanol-water mixture is accelerated many-fold in the presence of a 20 kHz ultrasonic field. The thickness of the silica shell can be easily controlled in the range of several nanometers during sonication. Mossbauer spectra revealed that nonsuperparamagnetic behavior of obtained core-shell NPs is mostly related to the dipole-dipole interactions of magnetic cores and not to the particle size effect. Core-shell Fe(3)O(4)@SiO(2) NPs prepared with sonochemistry exhibit a higher magnetization value than that for NPs obtained under silent conditions owing to better control of the deposited silica quantities as well as to the high speed of sonochemical coating, which prevents the magnetite from oxidizing.
ACS Nano 2008 May
PMID:Sonochemical approach to the synthesis of Fe(3)O(4)@SiO(2) core-shell nanoparticles with tunable properties. 1920 81

Drug delivery, magnetic resonance and fluorescence imaging, magnetic manipulation, and cell targeting are simultaneously possible using a multifunctional mesoporous silica nanoparticle. Superparamagnetic iron oxide nanocrystals were encapsulated inside mesostructured silica spheres that were labeled with fluorescent dye molecules and coated with hydrophilic groups to prevent aggregation. Water-insoluble anticancer drugs were delivered into human cancer cells; surface conjugation with cancer-specific targeting agents increased the uptake into cancer cells relative to that in non-cancerous fibroblasts. The highly versatile multifunctional nanoparticles could potentially be used for simultaneous imaging and therapeutic applications.
ACS Nano 2008 May
PMID:Multifunctional inorganic nanoparticles for imaging, targeting, and drug delivery. 1920 85

Arrays of multiwalled carbon nanotubes doped with phosphorus (P) and nitrogen (N) are synthesized using a solution of ferrocene, triphenyl-phosphine, and benzylamine in conjunction with spray pyrolysis. We demonstrate that iron phosphide (Fe(3)P) nanoparticles act as catalysts during nanotube growth, leading to the formation of novel PN-doped multiwalled carbon nanotubes. The samples were examined by high resolution electron microscopy and microanalysis techniques, and their chemical stability was explored by means of thermogravimetric analysis in the presence of oxygen. The PN-doped structures reveal important morphology and chemical changes when compared to N-doped nanotubes. These types of heterodoped nanotubes are predicted to offer many new opportunities in the fabrication of fast-response chemical sensors.
ACS Nano 2008 Mar
PMID:Heterodoped nanotubes: theory, synthesis, and characterization of phosphorus-nitrogen doped multiwalled carbon nanotubes. 1920 68

We demonstrate the development and successful application of immunotargeted superparamagnetic iron oxide nanoparticles (ITSIONs), with in vivo magnetic resonance diagnostic and potential drug delivery capability for kidney disease. Further, the versatility of the conjugation chemistry presents an attractive route to the preparation of a range of biomolecule-nanoparticle conjugates. The ITSION contrast agent is a stable, biocompatible, targeted nanoparticle complex that combines a monodisperse iron oxide nanoparticle core with a functionalized phospholipid coating conjugated to antibodies that is capable of targeting normal cells expressing specific target antigens. The plasma half-life and R1 and R2 relaxivities suggest sufficient time for targeted binding while clearing from the system quick enough for detection of specific contrast enhancement. RT1 anti-MHC Class II antibodies were used to target the renal medulla of the rat, a section of the kidney in which MHC Class II, associated with inflammation, is specifically expressed. For in vivo resonance imaging, we compare phospholipid coated nanoparticles, nonspecific ITSIONs, and RT1 ITSIONs. Enhanced binding of the RT1 ITSIONS indicates specificity for the renal medulla and thus potential for disease detection or drug delivery.
ACS Nano 2008 Mar
PMID:Magnetic resonance imaging of major histocompatibility class II expression in the renal medulla using immunotargeted superparamagnetic iron oxide nanoparticles. 1920 73


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