The Experts below are selected from a list of 17382 Experts worldwide ranked by ideXlab platform

Chang-guo Zhan - One of the best experts on this subject based on the ideXlab platform.

  • Reaction pathway for cocaine hydrolase-Catalyzed Hydrolysis of (+)-cocaine
    Theoretical Chemistry Accounts, 2015
    Co-Authors: Fang Zheng, Chang-guo Zhan
    Abstract:

    A recently designed and discovered cocaine hydrolase (CocH), engineered from human butyrylcholinesterase, has been proven promising as a novel enzyme therapy for treatment of cocaine overdose and addiction because it is highly efficient in catalyzing Hydrolysis of naturally occurring (−)-cocaine. It has been known that the CocH also has a high catalytic efficiency against (+)-cocaine, a synthetic enantiomer of cocaine. Reaction pathway and the corresponding free energy profile for the CocH-Catalyzed Hydrolysis of (+)-cocaine have been determined, in the present study, by performing first-principles pseudobond quantum mechanical/molecular mechanical free energy (QM/MM-FE) calculations. According to the QM/MM-FE results, the catalytic Hydrolysis process is initiated by the nucleophilic attack on carbonyl carbon of (−)-cocaine benzoyl ester via hydroxyl oxygen of S198 side chain, and the second reaction step (i.e., dissociation of benzoyl ester) is rate-determining. This finding for CocH-Catalyzed Hydrolysis of (+)-cocaine is remarkably different from that for the (+)-cocaine Hydrolysis Catalyzed by bacterial cocaine esterase in which the first reaction step of the deacylation is associated with the highest free energy barrier (~17.9 kcal/mol). The overall free energy barrier (~16.0 kcal/mol) calculated for the acylation stage of CocH-Catalyzed Hydrolysis of (+)-cocaine is in good agreement with the experimental free energy barrier of ~14.5 kcal/mol derived from the experimental kinetic data.

  • Reaction pathways and free energy profiles for cholinesterase-Catalyzed Hydrolysis of 6-monoacetylmorphine
    Organic & biomolecular chemistry, 2014
    Co-Authors: Yan Qiao, Ke-li Han, Chang-guo Zhan
    Abstract:

    As the most active metabolite of heroin, 6-monoacetylmorphine (6-MAM) can penetrate into the brain for the rapid onset of heroin effects. The primary enzymes responsible for the metabolism of 6-MAM to the less potent morphine in humans are acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). The detailed reaction pathways for AChE- and BChE-Catalyzed Hydrolysis of 6-MAM to morphine have been explored, for the first time, in the present study by performing first-principles quantum mechanical/molecular mechanical free energy calculations. It has been demonstrated that the two enzymatic reaction processes follow similar catalytic reaction mechanisms, and the whole catalytic reaction pathway for each enzyme consists of four reaction steps. According to the calculated results, the second reaction step associated with the transition state TS2a/TS2b should be rate-determining for the AChE/BChE-Catalyzed Hydrolysis, and the free energy barrier calculated for the AChE-Catalyzed Hydrolysis (18.3 kcal mol−1) is 2.5 kcal mol−1 lower than that for the BChE-Catalyzed Hydrolysis (20.8 kcal mol−1). The free energy barriers calculated for the AChE- and BChE-Catalyzed reactions are in good agreement with the experimentally derived activation free energies (17.5 and 20.7 kcal mol−1 for the AChE- and BChE-Catalyzed reactions, respectively). Further structural analysis reveals that the aromatic residues Phe295 and Phe297 in the acyl pocket of AChE (corresponding to Leu286 and Val288 in BChE) contribute to the lower energy of TS2a relative to TS2b. The obtained structural and mechanistic insights could be valuable for use in future rational design of a novel therapeutic treatment of heroin abuse.

  • Reaction pathway and free energy profile for butyrylcholinesterase-Catalyzed Hydrolysis of acetylcholine.
    The journal of physical chemistry. B, 2010
    Co-Authors: Xi Chen, Lei Fang, Junjun Liu, Chang-guo Zhan
    Abstract:

    A catalytic mechanism for the butyrylcholinesterase (BChE)-Catalyzed Hydrolysis of acetylcholine (ACh) has been studied by performing pseudobond first-principles quantum mechanical/molecular mechanical-free energy calculations on both acylation and deacylation of BChE. It has been shown that the acylation with ACh includes two reaction steps, including nucleophilic attack on the carbonyl carbon of ACh and dissociation of choline ester. The deacylation stage includes nucleophilic attack of a water molecule on the carboxyl carbon of the substrate and dissociation between the carboxyl carbon of the substrate and the hydroxyl oxygen of the Ser198 side chain. Notably, despite the fact that acetylcholinesterase (AChE) and BChE are very similar enzymes, the acylation of BChE with ACh is rate-determining, which is remarkably different from the AChE-Catalyzed Hydrolysis of ACh, in which the deacylation is rate-determining. The computational prediction is consistent with available experimental kinetic data. The overall free energy barrier calculated for BChE-Catalyzed Hydrolysis of ACh is 13.8 kcal/mol, which is in good agreement with the experimentally derived activation free energy of 13.3 kcal/mol.

  • Theoretical studies of the transition-state structures and free energy barriers for base-Catalyzed Hydrolysis of amides.
    Journal of Physical Chemistry A, 2006
    Co-Authors: Ying Xiong, Chang-guo Zhan
    Abstract:

    The transition-state structures and free energy barriers for the rate-determining step (i.e. the formation of a tetrahedral intermediate) of base-Catalyzed Hydrolysis of a series of amides in aqueous solution have been studied by performing first-principle electronic structure calculations using a hybrid supermolecule-polarizable continuum approach. The calculated results and a revisit of recently reported experimental proton inventory data reveal that the favorable transition-state structure optimized for the tetrahedral intermediate formation of hydroxide ion-Catalyzed Hydrolysis of formamide may have three solvating water molecules remaining on the attacking hydroxide oxygen and two additional water molecules attached to the carbonyl oxygen of formamide. The calculated results have also demonstrated interesting substituent effects on the optimized transition-state geometries, on the transition-state stabilization, and on the calculated free energy barriers for the base-Catalyzed Hydrolysis of amides. W...

  • Catalytic Mechanism and Energy Barriers for Butyrylcholinesterase-Catalyzed Hydrolysis of Cocaine
    Biophysical journal, 2005
    Co-Authors: Chang-guo Zhan, Daquan Gao
    Abstract:

    The geometries of the transition states, intermediates, and prereactive enzyme-substrate complex and the corresponding energy barriers have been determined by performing hybrid quantum mechanical/molecular mechanical (QM/MM) calculations on butyrylcholinesterase (BChE)-Catalyzed Hydrolysis of (−)- and (+)-cocaine. The energy barriers were evaluated by performing QM/MM calculations with the QM method at the MP2/6-31+G* level and the MM method using the AMBER force field. These calculations allow us to account for the protein environmental effects on the transition states and energy barriers of these enzymatic reactions, showing remarkable effects of the protein environment on intermolecular hydrogen bonding (with an oxyanion hole), which is crucial for the transition state stabilization and, therefore, on the energy barriers. The calculated energy barriers are consistent with available experimental kinetic data. The highest barrier calculated for BChE-Catalyzed Hydrolysis of (−)- and (+)-cocaine is associated with the third reaction step, but the energy barrier calculated for the first step is close to the highest and is so sensitive to the protein environment that the first reaction step can be rate determining for (−)-cocaine Hydrolysis Catalyzed by a BChE mutant. The computational results provide valuable insights into future design of BChE mutants with a higher catalytic activity for (−)-cocaine.

Oleg G. Sinyashin - One of the best experts on this subject based on the ideXlab platform.

  • Luminescent silica nanoparticles for sensing acetylcholinesterase-Catalyzed Hydrolysis of acetylcholine
    Biosensors & bioelectronics, 2015
    Co-Authors: Alsu R. Mukhametshina, Svetlana V. Fedorenko, Irina V. Zueva, Konstantin A. Petrov, Patrick Masson, Irek R. Nizameev, Asiya R. Mustafina, Oleg G. Sinyashin
    Abstract:

    This work highlights the H-function of Tb(III)-doped silica nanoparticles in aqueous solutions of acetic acid as a route to sense acetylcholinesterase-Catalyzed Hydrolysis of acetylcholine (ACh). The H-function results from H(+)-induced quenching of Tb(III)-centered luminescence due to protonation of Tb(III) complexes located close to silica/water interface. The H-function can be turned on/switched off by the concentration of complexes within core or nanoparticle shell zones, by the silica surface decoration and adsorption of both organic and inorganic cations on silica surface. Results indicate the optimal synthetic procedure for making nanoparticles capable of sensing acetic acid produced by enzymatic Hydrolysis of acetylcholine. The H-function of nanoparticles was determined at various concentrations of ACh and AChE. The measurements show experimental conditions for fitting the H-function to Michaelis-Menten kinetics. Results confirm that reliable fluorescent monitoring AChE-Catalyzed Hydrolysis of ACh is possible through the H-function properties of Tb(III)-doped silica nanoparticles.

Jun Wang - One of the best experts on this subject based on the ideXlab platform.

  • Hydrothermal synthesis of nanocrystalline zeolite Beta by acid-Catalyzed Hydrolysis of teraethylorthosilicate
    Materials Chemistry and Physics, 2011
    Co-Authors: Fangfang Cao, Jun Wang
    Abstract:

    Abstract Nanocrystalline zeolite Beta was synthesized via the acid-Catalyzed Hydrolysis of teraethylorthosilicate (TEOS) under static hydrothermal conditions. Various parameters, such as pH value for hydrolyzing TEOS, SiO2/Al2O3 ratio, template content, crystallization temperature and time, were investigated to obtain the suitable synthesis conditions. The produced samples were characterized by XRD, SEM, TEM, IR, ICP, surface areas, pore volumes and pore distributions. Compared with the traditional base-Catalyzed Hydrolysis of TEOS, the silicate precursors created by the acid-Catalyzed Hydrolysis of TEOS are proved to be favorable to the formation of nanocrystalline zeolite Beta.

  • Facile synthesis of small crystal ZSM-5 zeolite by acid-Catalyzed Hydrolysis of tetraethylorthosilicate
    Science China-chemistry, 2009
    Co-Authors: Yajing Wu, Youdong Lu, Jun Wang
    Abstract:

    Small crystal zeolites ZSM-5 with sizes of 150–300 nm were synthesized using the colloidal silicate precursors as the silica source created by the acid-Catalyzed Hydrolysis of tetraethylorthosilicate with tetrapropylammonium bromide as the structure-directing agent within a short crystallization time of 20–35 h. The precursors and final products were detected by XRD, SEM, ICP and DLS.

  • Rapid synthesis of zeolite MCM-22 by acid-Catalyzed Hydrolysis of tetraethylorthosilicate
    Materials Letters, 2008
    Co-Authors: Xiaoqian Ren, Jun Wang
    Abstract:

    Abstract Using tetraethylorthosilicate (TEOS) as the silica source, zeolite MCM-22 was hydrothermally synthesized with the acid-Catalyzed Hydrolysis of TEOS to produce siliceous precursors, followed by the addition of the alumina source and the structure-directing agent (hexamethyleneimine (HMI)), and the crystallization in a basic media. The acid used for catalyzing the Hydrolysis of TEOS and the HMI/SiO 2 ratio were changed to investigate their effects on the crystallization of MCM-22. The resultant materials were characterized by XRD, SEM, N 2 adsorption and ICP techniques. It is found that the well crystallized MCM-22 can be successfully synthesized through the acid-Catalyzed Hydrolysis of TEOS, and hydrochloric acid is most effective in the Hydrolysis of TEOS for synthesizing MCM-22 with a very short crystallization time of only 30 h. Moreover, with this synthesis route, it is also possible to obtain MCM-22 at a very low concentration of HMI with the HMI/SiO 2 molar ratio of 0.1.

Alsu R. Mukhametshina - One of the best experts on this subject based on the ideXlab platform.

  • Luminescent silica nanoparticles for sensing acetylcholinesterase-Catalyzed Hydrolysis of acetylcholine
    Biosensors & bioelectronics, 2015
    Co-Authors: Alsu R. Mukhametshina, Svetlana V. Fedorenko, Irina V. Zueva, Konstantin A. Petrov, Patrick Masson, Irek R. Nizameev, Asiya R. Mustafina, Oleg G. Sinyashin
    Abstract:

    This work highlights the H-function of Tb(III)-doped silica nanoparticles in aqueous solutions of acetic acid as a route to sense acetylcholinesterase-Catalyzed Hydrolysis of acetylcholine (ACh). The H-function results from H(+)-induced quenching of Tb(III)-centered luminescence due to protonation of Tb(III) complexes located close to silica/water interface. The H-function can be turned on/switched off by the concentration of complexes within core or nanoparticle shell zones, by the silica surface decoration and adsorption of both organic and inorganic cations on silica surface. Results indicate the optimal synthetic procedure for making nanoparticles capable of sensing acetic acid produced by enzymatic Hydrolysis of acetylcholine. The H-function of nanoparticles was determined at various concentrations of ACh and AChE. The measurements show experimental conditions for fitting the H-function to Michaelis-Menten kinetics. Results confirm that reliable fluorescent monitoring AChE-Catalyzed Hydrolysis of ACh is possible through the H-function properties of Tb(III)-doped silica nanoparticles.

William P. Huskey - One of the best experts on this subject based on the ideXlab platform.

  • nitrogen isotope effects on acetylcholinesterase Catalyzed Hydrolysis of omicron nitroacetanilide
    Journal of the American Chemical Society, 1993
    Co-Authors: Muralikrishna Rao, P N Barlow, Alton N Pryor, Pyotr Paneth, Marion H Oleary, Daniel M. Quinn, William P. Huskey
    Abstract:

    The nitrogen-15 isotope effect on V/K for Electrophorus electricus acetylcholinesterase-Catalyzed Hydrolysis of o-nitroacetanilide has been determined by isotope ratio mass spectrometry. The effect determined in buffered H 2 O (0.1 M sodium phosphate, 0.1 N NaCl, pH 7.3, 25 o C) is 15 V/K=1.0119±0.0005. A small though palpable decrease of the isotope effect is observed when the reaction is run in equivalently buffered D 2 O (pD=7.7), 15 V/K=1.0106±0.0002. The corresponding solvent isotope effect is D V/K=1.56±0.03