Ab initio SCF energy calculations of the rotational orientation of each of the exocyclic groups of 6-O-methyl-β-d-tagatofuranose (original) (raw)
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The hydrolyses of .alpha.-D-ribose and -glucose 1-phosphates
The Journal of Organic Chemistry, 1969
aD -Ribofuranose 1-phosphate is several hundred times as reactive as a-&glucopyranose 1-phosphate in both the acid-catalyzed hydrolysis and the hydrolysis of the undissociated phosphate. The activation energy for the acid hydrolysis is 6 kcal mol-' lower for the ribose phosphate. Hydrolysis of the ribose phosphate monoanion makes no contribution to the overall reaction. The catalytic efficiencies of the mineral acids for the hydrolysis of glucose 1-phosphate are HC1> HClO, N HBO,, and the positive salt effects of sodium chloride are considerably greater than those of sodium perchlorate.
Carbohydrate Research, 2014
We present an extensive computational study of a complex conformational isomerism of two gas phase pentoses of biological and potential astrobiological importance, D-ribose and 2-deoxy-D-ribose. Both cyclic (a-and b-pyranoses, aand b-furanoses) and open-chain isomers have been probed using second order Møller-Plesset perturbation theory (MP2), M06-2X density functional, and multi-level G4 methods. This study revealed a multitude of existing minima structures. Numerous furanose conformers found are described with the Altona and Sundaralingam pseudorotation parameters. In agreement with the recent gas-phase microwave (MW) investigation of Cocinero et al., the calculated free ribose isomers of lowest energy are the two b-pyranoses with the 1 C 4 and 4 C 1 ring chair conformations. Both b-pyranoses lie within 0.9 kJ/mol in terms of DG(298 K) (G4), thus challenge the computational methods used to predict the ribose global minimum. The calculated most favoured ribofuranose is the a-anomer having the twist 2 T 1 ring conformation, put 10.4 kJ/mol higher in DG than the global minimum. By contrast with D-ribose, the lowest energy 2-deoxy-D-ribose is the a-pyranose, with the most stable 2-deoxy-D-furanose (the aanomer) being only 6.2 kJ/mol higher in free energy. For both pentoses, the most favoured open-chain isomers are significantly higher in energy than the low-lying cyclic forms. A good overall agreement is observed between the M06-2X and MP2 results in terms of both the existing low-energy minima structures and intramolecular H-bonding geometrical parameters. The natural orbital analysis confirms the occuring of the endo-and exo-anomeric effects and maximization of intramolecular H-bonding in the lowest-lying pyranoses and furanoses of both sugars.
Journal of Molecular Biology, 1995
Kinetic and crystallographic studies have characterized the effect of Research & Biotechnology 2-deoxy-glucose 6-phosphate on the catalytic and structural properties of The National Hellenic glycogen phosphorylase b. Previous work on the binding of glucose 6-phosphate, a potent physiological inhibitor of the enzyme, to T state Research Foundation, 48 Vas Constantinou Ave, Athens phosphorylase b in the crystal showed that the inhibitor binds at the 11635, Greece allosteric site and induces substantial conformational changes that affect the subunit-subunit interface. The hydrogen-bond from the O-2 hydroxyl of 2 Laboratory of Molecular glucose 6-phosphate to the main-chain oxygen of Val40' represents the only Biophysics, University of hydrogen bond from the sugar to the other subunit, and this interaction Oxford, Rex Richards appears important for promoting a more ''tensed'' structure than native T Building, South Parks Road state phosphorylase b. 2-Deoxy-glucose 6-phosphate acts competitively Oxford, OX1 3QU, UK with both the activator AMP and the substrate glucose 1-phosphate, with K i values of 0.53 mM and 1.23 mM, respectively. The binding of 3 School of Biology & 2-deoxy-glucose 6-phosphate to T state glycogen phosphorylase b in the Biochemistry, University of crystal, has been investigated and the complex phosphorylase b: Bath, Claverton Down 2-deoxy-glucose 6-phosphate has been refined to give a crystallographic R Bath, BA2 7AY, UK
Ab initio molecular orbital calculations on furanose sugars: a study with the 6–31G basis set
Carbohydrate Research, 1990
Ab initio molecular orbital calculations were performed on 2-deoxy-@g[ycero-tetrofuranose (1) using the 6-3 lG* basis set to evaluate the effect of ring conformation on the molecular parameters (bond lengths, angles, and torsions). Geometric optimizations were conducted on the planar and ten envelope conformers of 1, and these data were compared to those obtained from previous calculations using the STO-3G and 3-21G basis sets. Conformational energy profiles derived from 3-21G and 6-31G* data were found to be qualitatively comparable. The effect of furanose ring conformation on key bond lengths (e.g., C-H, CO), bond angles (e.g., COC), and bond torsions (e.g., the exoanomeric C-l&G-l torsion) was examined, and a qualitative agreement was observed between the 3-21G and 6-31G* analyses. The results indicate that, for semi-quantitative ab initio studies of intact carbohydrates, the 3-21G basis set is sufficient, and that the STO-3G basis set should not be employed unless crude structural approximations are desired. The observed concerted behavior of C-0 bond lengths in the vicinity of the anomeric carbon of the aldofuranose ring has suggested a possible role of C-l-O-1 bond orientation in affecting the mechanism of glycoside bond hydrolysis.
The enzymatic hydrolysis of the phosphate ester bond in some thionucleotides
Biochimica et biophysica acta, 1979
We prepared the 5'- and 3'-O-phosphorothioate esters of the antitumor agent O2 : 2'-anhydro-1-beta-D-arabinosylcytosine. We also included in this study esters of 2'-thio-2'-deoxycytidine, namely, 2'-S-dCyd-2' : 3'-P, 2'-S-dCyd-2'-P, and 2'-S-dCyd-3'-P, along with natural nucleotides. These compounds were subjected to the action of Escherichia coli alkaline phosphatase, potato acid phosphatase, and bovine pancreatic ribonuclease A. The data were analyzed by Lineweaver-Burk plots to obtain Km and KI values. Only 2'-S-dCyd-2'-P was a substrate for alkaline phosphatase; the anhydro-araCyt phosphorothioates were good competitive inhibitors, while 2'-S-dCyd-3'-P did not associate with the enzyme. Acid phosphatase hydrolyzed all four monoesters investigated, including the S-phosphorothioate. The cyclic phosphorothioate, 2'-S-dCyd-2' : 3'-P was neither hydrolyzed by, nor associated with, ribonuclease A. ORD spectros...
Computational mechanistic study of human liver glycerol 3‐phosphate dehydrogenase using ONIOM method
Journal of Physical Organic Chemistry, 2020
Human liver glycerol 3-phosphate dehydrogenase catalyzes transfer of a hydride anion from NADH to dihydroxyacetone phosphate (DHAP) forming L-glycerol 3-phosphate and NAD + in a single step reaction. It is proposed that a hydride ion is transferred from NADH to the carbonyl carbon of DHAP through a general acid catalysis in which the carbonyl oxygen of DHAP is protonated by a nearby acidic residue. Based on the crystal structure of enzyme, it was suggested that one of the active site lysine residues (Lys120/Lys204) might act as general acid for the protonation of the carbonyl oxygen at DHAP. In this study, we formulated a number of computational systems to study the hydride transfer mechanism including main active site amino acid side chains, NADH cofactor, and DHAP. The calculations involved ONIOM method consisting of DFT and molecular mechanics (MM). We evaluated the energetics of the hydride transfer process in different model systems while probing the roles of active site residues, Lys120/Lys204/Asp260. Based on calculations, protonated Asp260 has more favorable energetics to act as the general acid catalysis as compared to Lys120/204 residues.
The Journal of Chemical Thermodynamics, 2009
a-D-Galactose 1-phosphate sn-Glycerol 3-phosphate 4-Nitrophenyl phosphate Phosphocreatine 3-Phospho-D-glycerate Calorimetry Standard Gibbs free energy and enthalpy a b s t r a c t Microcalorimetry, high-performance liquid chromatography (h.p.l.c.), and an enzymatic assay have been used to conduct a thermodynamic investigation of five phosphate hydrolysis reactions: {a-D-galactose 1-phosphate(aq) + H 2 O(l) = D-galactose(aq) + orthophosphate(aq)} (1), {sn-glycerol 3-phosphate(aq) + H 2 O(l) = glycerol(aq) + orthophosphate(aq)} (2), {4-nitrophenyl phosphate(aq) + H 2 O(l) = 4-nitrophenol(aq) + orthophosphate(aq)} (3), {phosphocreatine(aq) + H 2 O(l) = creatine(aq) + orthophosphate(aq)} (4), and {3-phospho-D-glycerate(aq) + H 2 O(l) = D-glycerate(aq) + orthophosphate(aq)} (5). Calorimetrically determined enthalpies of reaction D r H(cal) were measured for reactions and the apparent equilibrium constant K 0 was measured for reaction (2). The pKs and standard enthalpies of reaction D r H for the H + and Mg 2+ binding reactions of the reactants and products in the aforementioned reactions were obtained either from the literature or by estimation. A chemical equilibrium model was then used to calculate standard equilibrium constants K and standard enthalpies of reaction D r H for chemical reference reactions that correspond to the overall biochemical reactions that were studied experimentally. Property values from the literature and thermodynamic network calculations were used to obtain values of the equilibrium constants for the chemical reference reactions that correspond to the overall biochemical reactions (1). These values were compared with other results from the literature and also correlated with structural features. The results obtained in this study can be used in the chemical equilibrium model to calculate values of K 0 , the standard apparent Gibbs free energy changes D r G 0 , the standard apparent enthalpy changes D r H 0 , changes in binding of the proton D r N(H + ), and the position of equilibrium for the overall biochemical reactions considered in this study over a reasonably wide range of temperature, pH, pMg [Àlog 10 {m(Mg 2+ )/m°}], and ionic strength I. Values of K 0 and D r G 0°u nder approximately physiological conditions (T = 310.15 K, pH 7.0, pMg = 3.0, and I m = 0.25 mol Á kg À1 ) have been calculated.
Journal of Computational Chemistry, 2003
The second step in the enzyme-catalyzed hydrolysis of phosphate esters by ribonuclease A (RNase A) was studied using an ab initio quantum-based model of the active site including constrained parts of three critical residues, His-12, His-119, and Lys-41, and a small substrate. The competition between release of the cyclic phosphate intermediate and subsequent hydrolysis following transphosphorylation was explored to determine the electronic factors that contribute to preferential intermediate product release observed experimentally. The structural and energetic results obtained at both the RHF and MP2 levels reveal several contributing factors consistent with experimental observation. Although the intrinsic electronic effects tend to favor hydrolysis slightly with an overall activation free energy of approximately 70 kJ mol Ϫ1 , entropic and environmental effects favor release of the cyclic phosphate intermediate over hydrolysis. Exploration of the second, hydrolysis step also revealed interesting similarity with the transphosphorylation step, including the observation of autocatalysis by the substrate. Moreover, both steps of the overall RNase A reaction reveal multiple pathways involving proton transfers to sites of similar proton affinities. The anionic phosphate in both steps can act as a stable proton binding site as protons are moved around the active site throughout the progress of the reaction. These results suggest autocatalysis may be representative of more general behavior in enzymes containing highly charged substrates, especially phosphates.