Search results for "Active site"
showing 10 items of 184 documents
Detoxication of carcinogenic fjord-region diol epoxides of polycyclic aromatic hydrocarbons by glutathione transferase P1-1 variants and glutathione.
1998
AbstractEpidemiological studies suggest that individuals differing in the expression of allelic variants of the human glutathione transferase (GST) Pi gene differ in susceptibility to chemical carcinogens such as polycyclic aromatic hydrocarbons (PAH). This study reports the catalytic efficiencies (kcat/Km) of two naturally occurring variants, GSTP1-1/I-105 and GSTP1-1/V-105, towards a series of fjord-region diol epoxides representing potent biologically active PAH metabolites, and two GSTP1-1 mutants with Ala105 and Trp105 in the active site. The results indicate that individuals who are homozygous for the allele encoding GSTP1-1/V-105 might be more susceptible to PAH carcinogenesis due to…
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…
Hydrolysis of Phosphotriesters: A Theoretical Analysis of the Enzymatic and Solution Mechanisms
2012
A theoretical study on the alkaline hydrolysis of paraoxon, one of the most popular organophosphorus pesticides, in aqueous solution and in the active site of Pseudomonas diminuta phosphotriesterase (PTE) is presented. Simulations by means of hybrid quantum mechanics/molecular mechanics (QM/MM) potentials show that the hydrolysis of paraoxon takes place through an A(N)D(N) or associative mechanism both in solution and in the active site of PTE. The results correctly reproduce the magnitude of the activation free energies and can be used to rationalize the observed kinetic isotope effects (KIEs) for the hydrolysis of paraoxon in both media. Enzymatic hydrolysis of O,O-diethyl p-chlorophenyl …
Multiscale Simulations of SARS-CoV-2 3CL Protease Inhibition with Aldehyde Derivatives. Role of Protein and Inhibitor Conformational Changes in the R…
2021
We here investigate the mechanism of SARS-CoV-2 3CL protease inhibition by one of the most promising families of inhibitors, those containing an aldehyde group as a warhead. These compounds are covalent inhibitors that inactivate the protease, forming a stable hemithioacetal complex. Inhibitor 11a is a potent inhibitor that has been already tested in vitro and in animals. Using a combination of classical and QM/MM simulations, we determined the binding mode of the inhibitor into the active site and the preferred rotameric state of the catalytic histidine. In the noncovalent complex, the aldehyde group is accommodated into the oxyanion hole formed by the NH main-chain groups of residues 143 …
Catecholato complexes of o-phenylenebis(salicylideneiminato)iron(III) and meso-tetra(parasulphonatephenyl)porphyrinatoferrate(III). A comment on the …
1986
Abstract Formation of catecholato complexes of Fe(saloph) + and Fe(TPPS) 3− in solution is studied. Fe(saloph)(cat) − contains a cat 2− bidentate ligand. Its formation in solution competes efficiently with the hydrolysis and dimerization of Fe(saloph) + to give Fe 2 (saloph) 2 O. This behaviour shows that the planar saloph 2− ligand, as the analogous salen 2− , is easily distorted, and is not as rigid as generally considered. Iron(III) porphyrin Fe(TPPS) 3− with catechol gives the complex [Fe(TPPS)(Hcat)] 4− . Deprotonation of the unidentate Hcat − ligand cannot be studied because the smaller stability of the complex, and the dimerization of the metalloporphyrin dominates in basic medium. T…
ChemInform Abstract: Bioinspired Functional Analogs of the Active Site of Molybdenum Enzymes: Intermediates and Mechanisms
2015
Abstract Molybdenum(VI) complexes of the general type MoVI(L)2(E)O (L = 2-(aryl N CH)-pyrrolylato, E = O, NtBu) and their relevance as bioinspired functional analogs for molybdenum-containing oxotransferases are reviewed. All complexes are capable of transfering oxygen atoms to PR3 (forward oxygen atom transfer) giving OPR3 and phosphane molybdenum(IV) complexes MoIV(L)2(E)(PR3) (with a second equivalent PR3) via the transient phosphoryl complex MoIV(L)2(E)(OPR3) and the five-coordinate intermediate MoIV(L)2(E). Reactivity of MoIV(L)2(E) and the favored stereochemistry of products from excess PR3 MoIV(L)2(E)(PR3) depend on the steric demand of the chelate ligands (L)−, the π donor ligand E …
Bioinspired functional analogs of the active site of molybdenum enzymes: Intermediates and mechanisms
2015
Abstract Molybdenum(VI) complexes of the general type MoVI(L)2(E)O (L = 2-(aryl N CH)-pyrrolylato, E = O, NtBu) and their relevance as bioinspired functional analogs for molybdenum-containing oxotransferases are reviewed. All complexes are capable of transfering oxygen atoms to PR3 (forward oxygen atom transfer) giving OPR3 and phosphane molybdenum(IV) complexes MoIV(L)2(E)(PR3) (with a second equivalent PR3) via the transient phosphoryl complex MoIV(L)2(E)(OPR3) and the five-coordinate intermediate MoIV(L)2(E). Reactivity of MoIV(L)2(E) and the favored stereochemistry of products from excess PR3 MoIV(L)2(E)(PR3) depend on the steric demand of the chelate ligands (L)−, the π donor ligand E …
Ferricytochrome c encapsulated in silica hydrogels: correlation between active site dynamics and solvent structure.
2003
Ferricytochrome c encapsulated in silica hydrogels has been prepared by the sol-gel technique following, with some modifications, the procedure originally developed by Ellerby et al. (Science 255 1113 (1992)). A suitable preparation of hydrogels enables having both 'wet' and 'dry' samples. Wet samples have a high water content: as the temperature is lowered below approximately 260 K, water freezes and the samples crack. On the contrary, dry samples have a low water content (hydration h approximately equal 0.35): in these conditions water does not freeze even at cryogenic temperatures and the samples remain transparent and non-cracking. The dynamics of ferricytochrome c and its dependence on…
On Transition Structures for Hydride Transfer Step in Enzyme Catalysis. A Comparative Study on Models of Glutathione Reductase Derived from Semiempir…
1996
As a model of the chemical reactions that take place in the active site of gluthatione reductase, the nature of the molecular mechanism for the hydride transfer step has been characterized by means of accurate quantum chemical characterizations of transition structures. The calculations have been carried out with analytical gradients at AM1 and PM3 semiempirical procedures, ab initio at HF level with 3-21G, 4-31G, 6-31G, and 6-31G basis sets and BP86 and BLYP as density functional methods. The results of this study suggest that the endo relative orientation on the substrate imposed by the active site is optimal in polarizing the C4-Ht bond and situating the system in the neighborhood of the…
Switch between tyrosinase and catecholoxidase activity of scorpion hemocyanin by allosteric effectors
2008
AbstractPhenoloxidases and hemocyanins have similar type 3 copper centers although they perform different functions. Hemocyanins are oxygen carriers, while phenoloxidases (tyrosinase/catecholoxidase) catalyze the initial step in melanin synthesis. Tyrosinases catalyze two subsequent reactions, whereas catecholoxidases catalyze only the second one. Recent results indicate that hemocyanins can also function as phenoloxidases and here we show for the first time that hemocyanin can be converted to phenoloxidase. Furthermore, its substrate specificity can be switched between catecholoxidase and tyrosinase activity depending on effectors such as hydroxymethyl-aminomethan (Tris) and Mg2+-ions. Thi…