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Catalytic Steps (catalytic + step)
Selected AbstractsReaction mechanisms between methylamine and a few Schiff bases: Ab initio potential energy surfaces of a catalytic step in semicarbazide sensitive amino oxidases (SSAO)INTERNATIONAL JOURNAL OF QUANTUM CHEMISTRY, Issue 6 2001Giuliano Alagona Abstract The potential energy surfaces for the transamination reaction catalyzed by SSAO were explored for some of the possible reactants considered in a preliminary investigation (Comput Chem 2000, 24, 311). The proton transfer to methylamine (as a model of the catalytic base belonging to the enzyme active site),either from the keto or enol form of the reactant Schiff bases with one of the possible cofactors, pyridoxal phosphate, PLP (using as a model the pyridoxal ring protonated at N),was investigated. The enol form seems to be preferred in the region of the neutral intermediate, because even the keto form undergoes a spontaneous rearrangement to the enol form once the C, proton is delivered to methylamine, producing methylammonium. When the proton is returned back to the Schiff base (on C1), the adduct is about 1.4 kcal/mol more stable than the reactants, while a canonical electron distribution is obtainable only for the enol form. The proton transfer to methylamine was also studied in the presence of the other possible cofactor (para or ortho) topaquinone, TQ. A steep uphill pathway, similar to the keto-pyridoxal Schiff base one, is obtained using the Schiff base with pTQ, which requires a rearrangement to the final intermediate. On the contrary, using the oTQ structures with the quinonoid O on the same side of methylamine, the proton abstracted from the Schiff base goes spontaneously onto the other quinonoid oxygen. The effect on the barrier heights produced by the presence of a variety of functional groups in the vicinity of the pyridoxal ring nitrogen was also examined. © 2001 John Wiley & Sons, Inc. Int J Quant Chem, 2001 [source] The phosphate site of trehalose phosphorylase from Schizophyllum commune probed by site-directed mutagenesis and chemical rescue studiesFEBS JOURNAL, Issue 5 2008Christiane Goedl Schizophyllum commune,,,-trehalose phosphorylase utilizes a glycosyltransferase-like catalytic mechanism to convert its disaccharide substrate into ,- d -glucose 1-phosphate and ,- d -glucose. Recruitment of phosphate by the free enzyme induces ,,,-trehalose binding recognition and promotes the catalytic steps. Like the structurally related glycogen phosphorylase and other retaining glycosyltransferases of fold family GT-B, the trehalose phosphorylase contains an Arg507-XXXX-Lys512 consensus motif (where X is any amino acid) comprising key residues of its putative phosphate-binding sub-site. Loss of wild-type catalytic efficiency for reaction with phosphate (kcat/Km = 21 000 m,1·s,1) was dramatic (,107 -fold) in purified Arg507,Ala (R507A) and Lys512,Ala (K512A) enzymes, reflecting a corresponding change of comparable magnitude in kcat (Arg507) and Km (Lys512). External amine and guanidine derivatives selectively enhanced the activity of the K512A mutant and the R507A mutant respectively. Analysis of the pH dependence of chemical rescue of the K512A mutant by propargylamine suggested that unprotonated amine in combination with H2PO4,, the protonic form of phosphate presumably utilized in enzymatic catalysis, caused restoration of activity. Transition state-like inhibition of the wild-type enzyme A by vanadate in combination with ,,,-trehalose (Ki = 0.4 ,m) was completely disrupted in the R507A mutant but only weakened in the K512A mutant (Ki = 300 ,m). Phosphate (50 mm) enhanced the basal hydrolase activity of the K512A mutant toward ,,,-trehalose by 60% but caused its total suppression in wild-type and R507A enzymes. The results portray differential roles for the side chains of Lys512 and Arg507 in trehalose phosphorylase catalysis, reactant state binding of phosphate and selective stabilization of the transition state respectively. [source] DNA gyrase requirements distinguish the alternate pathways of Mu transpositionMOLECULAR MICROBIOLOGY, Issue 2 2003Tanya D. Sokolsky Summary The MuA transposase mediates transposition of bacteriophage Mu through two distinct mechanisms. The first integration event following infection occurs through a non-replicative mechanism. In contrast, during lytic growth, multiple rounds of replicative transposition amplify the phage genome. We have examined the influence of gyrase and DNA supercoiling on these two transposition pathways using both a gyrase-inhibiting drug and several distinct gyrase mutants. These experiments reveal that gyrase activity is not essential for integration; both lysogens and recombination intermediates are detected when gyrase is inhibited during Mu infection. In contrast, gyrase inhibition causes severe defects in replicative transposition. In two of the mutants, as well as in drug-treated cells, replicative transposition is almost completely blocked. Experiments probing for formation of MuA,DNA complexes in vivo reveal that this block occurs very early, during assembly of the transposase complex required for the catalytic steps of recombination. The findings establish that DNA structure-based signals are used differently for integrative and replicative transposition. We propose that transposase assembly, the committed step for recombination, has evolved to depend on different DNA /architectural signals to control the reaction outcome during these two distinct phases of the phage life cycle. [source] The Rate-Determining Step in the Rhodium,Xantphos-Catalysed Hydroformylation of 1-OcteneCHEMISTRY - A EUROPEAN JOURNAL, Issue 6 2008Erik Zuidema Dr. Abstract The rate-determining step in the hydroformylation of 1-octene, catalysed by the rhodium,Xantphos catalyst system, was determined by using a combination of experimentally determined 1H/2H and 12C/13C kinetic isotope effects and a theoretical approach. From the rates of hydroformylation and deuterioformylation, a small 1H/2H isotope effect of 1.2 was determined for the hydride moiety of the rhodium catalyst. 12C/13C isotope effects of 1.012(1) and 1.012(3) for the ,-carbon and ,-carbon atoms of 1-octene were determined, respectively. Both quantum mechanics/molecular mechanics (QM/MM) and full quantum mechanics calculations were carried out on the key catalytic steps, for "real-world" ligand systems, to clarify whether alkene coordination or hydride migration is the rate-determining step. Our calculations (21.4,kcal,mol,1) quantitatively reproduce the experimental energy barrier for CO dissociation (20.1,kcal,mol,1) starting at the (bisphosphane)RhH(CO)2 resting state. The barrier for hydride migration lies 3.8,kcal,mol,1 higher than the barrier for CO dissociation (experimentally determined trend ,3,kcal,mol,1). The computed 1H/2H and 12C/13C kinetic isotope effects corroborate the results of the energy analysis. [source] Biologically Active Compounds through Catalysis: Efficient Synthesis of N -(Heteroarylcarbonyl)- N,-(arylalkyl)piperazinesCHEMISTRY - A EUROPEAN JOURNAL, Issue 3 2004Kamal Kumar Dr. Abstract A practical route for the synthesis of new biologically active 5-HT2,A receptor antagonists has been developed. In only three catalytic steps, this class of central nervous system (CNS) active compounds can be synthesized efficiently with high diversity. As the initial step, an anti -Markovnikov addition of amines to styrenes provides an easy route to N -(arylalkyl)piperazines, which constitute the core structure of the active molecules. Here, base-catalyzed hydroamination reactions of styrenes with benzylated piperazine proceeded in high yield even at room temperature. After catalytic debenzylation, the free amines were successfully carbonylated with different aromatic and heteroaromatic halides and carbon monoxide to yield the desired compounds in good to excellent yields. The two key reactions, base-catalyzed hydroamination of styrenes and palladium-catalyzed aminocarbonylation of haloarenes/heterocycles, showed tolerance towards various functional groups, thereby demonstrating the potential to synthesize a wide variety of new derivatives of this promising class of pharmaceuticals. [source] | ||||||||||