Search results for "Enzyme catalysis"
showing 10 items of 60 documents
Role of Protein Flexibility in Enzymatic Catalysis: Quantum Mechanical−Molecular Mechanical Study of the Deacylation Reaction in Class A β-Lactamases
2002
We present a theoretical study of a mechanism for the hydrolysis of the acyl-enzyme complex formed by a class A beta-lactamase (TEM1) and an antibiotic (penicillanate), as a part of the process of antibiotic's inactivation by this type of enzymes. In the presented mechanism the carboxylate group of a particular residue (Glu166) activates a water molecule, accepting one of its protons, and afterward transfers this proton directly to the acylated serine residue (Ser70). In our study we employed a quantum mechanics (AM1)-molecular mechanics partition scheme (QM/MM) where all the atoms of the system were allowed to relax. For this purpose we used the GRACE procedure in which part of the system …
Chemical Ligation and Isotope Labeling to Locate Dynamic Effects during Catalysis by Dihydrofolate Reductase.
2015
Abstract Chemical ligation has been used to alter motions in specific regions of dihydrofolate reductase from E. coli and to investigate the effects of localized motional changes on enzyme catalysis. Two isotopic hybrids were prepared; one with the mobile N‐terminal segment containing heavy isotopes (2H, 13C, 15N) and the remainder of the protein with natural isotopic abundance, and the other one with only the C‐terminal segment isotopically labeled. Kinetic investigations indicated that isotopic substitution of the N‐terminal segment affected only a physical step of catalysis, whereas the enzyme chemistry was affected by protein motions from the C‐terminal segment. QM/MM studies support th…
Enzymatically catalyzed synthesis of photocrosslinkable oligophenols
2000
The HRP-catalyzed oligomerization of cinnamoyl-hydroquinone-ester and cinnamoyl-4-hydroxyanilide led to the formation of soluble polyphenols. The oligomers were synthexized in water/1,4-dioxane and in water/acetone mixtures and characterized by NMR, FTIR and SEC. Upon UV treatment of the homogenoes films the polyphenols were crosslinked due to [2+2]-cycloadditions of the cinnamoyl functions.
Elucidating the catalytic reaction mechanism of orotate phosphoribosyltransferase by means of X-ray crystallography and computational simulations
2020
15 p.-8 fig.-2 tab.1 graph. abst.+ 8 fig. supl.-1 tab. supl.
Transition structure selectivity in enzyme catalysis: a QM/MM study of chorismate mutase
2001
Two different transition structures (TSs) have been located and characterized for the chorismate conversion to prephenate in Bacillus subtilis chorismate mutase by means of hybrid quantum-mechanical/molecular-mechanical (QM/MM) calculations. GRACE software, combined with an AM1/CHARMM24/TIP3P potential, has been used involving full gradient relaxation of the position of ca. 3300 atoms. These TSs have been connected with their respective reactants and products by the intrinsic reaction coordinate (IRC) procedure carried out in the presence of the protein environment, thus obtaining for the first time a realistic enzymatic reaction path for this reaction. Similar QM/MM computational schemes h…
Transition structures for hydride transfer reactions in vacuo and their role in enzyme catalysis
1996
A general discussion as to the role of in vacuo transition structure in enzyme catalysis is presented. Quantum mechanical aspects are emphasized. The transition structures defined as saddle points ...
Enzyme-catalysed transformations of ent-kaurane diterpenoids
2005
Several acetyl derivatives of linearol, atractyligenin and atractylitriol were obtained through enzyme-catalysed acetylation and deacetylation reactions. In most reactions lipases showed regio- and stereoselective behaviour, allowing a family of novel compounds to be prepared. Fil: Monsalve, Leandro Nicolas. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Unidad de Microanálisis y Métodos Físicos en Química Orgánica. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Unidad de Microanálisis y Métodos Físicos en Química Orgánica; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y …
Chemoenzymatic Synthesis of Functional Sialyl LewisX Mimetics with a Heteroaromatic Core
2014
Functional mimetics of the sialyl Lewis(X) tetrasaccharide were prepared by the enzymatic sialylation of a 1,3-diglycosylated indole and a glycosyl azide, which was subsequently transformed into a 1,4-diglycosylated 1,2,3-triazole, by using the trans-sialidase of Trypanosoma cruzi. These compounds inhibited the binding of E-, L-, and P-selectin-coated nanoparticles to polyacrylamide-bound sialyl-Lewis(X) -containing neighboring sulfated tyrosine residues (sTyr/sLe(X) -PAA) at low or sub-millimolar concentrations. Except for E-selectin, the mimetics showed higher activities than the natural tetrasaccharide.
Increased dynamic effects in a catalytically compromised variant of Escherichia coli dihydrofolate reductase
2013
Isotopic substitution (15N, 13C, 2H) of a catalytically compromised variant of Escherichia coli dihydrofolate reductase, EcDHFR-N23PP/S148A, has been used to investigate the effect of these mutations on catalysis. The reduction of the rate constant of the chemical step in the EcDHFR-N23PP/S148A catalyzed reaction is essentially a consequence of an increase of the quasi-classical free energy barrier and to a minor extent of an increased number of recrossing trajectories on the transition state dividing surface. Since the variant enzyme is less well set up to catalyze the reaction, a higher degree of active site reorganization is needed to reach the TS. Although millisecond active site motion…
Do dynamic effects play a significant role in enzymatic catalysis? A theoretical analysis of formate dehydrogenase.
2010
A theoretical study of the protein dynamic effects on the hydride transfer between the formate anion and nicotinamide adenine dinucleotide (NAD + ), catalyzed by formate dehydrogenase (FDH), is presented in this paper. The analysis of free downhill molecular dynamic trajectories, performed in the enzyme and compared with the reaction in aqueous solution, has allowed the study of the dynamic coupling between the reacting fragments and the protein or the solvent water molecules, as well as an estimation of the dynamic effect contribution to the catalytic effect from calculation of the transmission coefficient in the enzyme and in solution. The obtained transmission coefficients for the enzyme…