A general acid–general base reaction mechanism for human brain aspartoacylase: A QM/MM study

2012 ◽  
Vol 980 ◽  
pp. 85-91 ◽  
Author(s):  
Chenghua Zhang ◽  
Xiaoqiang Liu ◽  
Ying Xue
Keyword(s):  
Reaction Mechanism ◽  
Human Brain ◽  
General Base ◽  
General Acid

Deuterium exchange of C-methyl protons in lumazine derivatives

1970 ◽  
Vol 48 (2) ◽  
pp. 263-270 ◽  
Author(s):  
J. M. McAndless ◽  
Ross Stewart
Keyword(s):  
Proton Magnetic Resonance ◽  
Proton Magnetic Resonance Spectroscopy ◽  
Acid Catalysis ◽  
Deuterium Exchange ◽  
Base Catalysis ◽  
Resonance Spectroscopy ◽  
Methyl Group ◽  
General Base ◽  
General Acid ◽  
Acid Catalyzed

Proton magnetic resonance spectroscopy has been used to examine the deuterium exchange of the methyl protons in two lumazine derivatives. The exchange occurs at the C-7 methyl group in 6,7,8-trimethyllumazine (2) and at the C-6 methyl group in 1,7-dihydro-6,7,8-trimethyllumazine (3). The former reaction is subject to both general acid- and general base-catalysis but the latter only to general acid-catalysis. Plausible mechanisms for the reactions of both compounds are advanced, involving in the case of 3, acid-catalyzed addition of water across the C6—N5 double bond.

General acid and general base catalysed hydrolysis of 4-Methyl- and 4-Nitro-phenylurea

1976 ◽  
Vol 29 (4) ◽  
pp. 925 ◽  
Author(s):  
KJ Mollett ◽  
CJ O'Conner
Keyword(s):  
Buffer Solutions ◽  
General Base ◽  
General Acid ◽  
Hydrolysis Of

The hydrolysis of 4-methyl-and 4-nitro-phenylureas has been studied in buffer solutions at 101.0�C from pH 0 to 14, and parameters for general acid and general base catalyses have been calculated.

Intramolecular Bifunctional General Base-General Acid-Catalysis of Ester Solvolysis

1963 ◽  
Vol 85 (3) ◽  
pp. 350-351 ◽  
Author(s):  
S. Morris. Kupchan ◽  
Stuart P. Eriksen ◽  
Yun-Teh. Shen
Keyword(s):  
Acid Catalysis ◽  
General Base ◽  
General Acid

Theoretical Studies of Catalysis by Carboxypeptidase A: Could Gas-Phase Calculations Support a Mechanism?

2003 ◽  
Vol 68 (11) ◽  
pp. 2055-2079 ◽  
Author(s):  
Alexandra Kilshtain-Vardi ◽  
Gil Shoham ◽  
Amiram Goldblum
Keyword(s):  
Gas Phase ◽  
Peptide Bond ◽  
Main Question ◽  
Carboxypeptidase A ◽  
Peptide Cleavage ◽  
Alternative Pathways ◽  
General Base ◽  
General Acid ◽  
Reduced Representations ◽  
Quantum Mechanical Computations

We compare recent quantum mechanical computations of alternative reaction pathways for carboxypeptidase A, a zinc proteinase, in an "enzyme environment" to similar calculations in the "gas phase" that include the minimal chemical entities that are required for a non-catalytic reaction. The main question that we address is whether anything may be learned from such reduced representations. Two general acid-general base alternative pathways and one nucleophilic pathway are compared. The original calculations were run on a relatively large model (120 atoms) of the active site of carboxypeptidase A which included zinc and its ligands, as well as the residues Arg145, Arg127, Glu270, a water molecule and a model dipeptide. The "gas-phase" pathways include only the dipeptide, water and Glu270 and serve as models for the non-catalytic pathway. The calculations were performed by semiempirical MNDO/H/d that includes modifications for d-orbital representations as well as for intra- and intermolecular multiple H-bond formation. The gas-phase results strengthen our previous conclusion about the preference for general acid-general base pathways for peptide cleavage by carboxypeptidase A rather than a "direct nucleophilic" pathway. The bottleneck of the reaction is proton transfer to the nitrogen in the peptide bond, preceding the peptide cleavage.

Concurrent general-acid and general-base catalysis of esterification

1970 ◽  
Vol 92 (14) ◽  
pp. 4377-4382 ◽  
Author(s):  
Sheldon. Milstien ◽  
Louis Arthur. Cohen
Keyword(s):  
Base Catalysis ◽  
General Base ◽  
General Acid

scholarly journals pH-dependence and structure–activity relationships in the papain-catalysed hydrolysis of anilides

1971 ◽  
Vol 124 (1) ◽  
pp. 117-122 ◽  
Author(s):  
G. Lowe ◽  
Y. Yuthavong
Keyword(s):  
Acid Catalysis ◽  
Ph Dependence ◽  
Base Catalysis ◽  
General Base ◽  
Structure Activity ◽  
Equilibrium Binding ◽  
General Acid ◽  
Leaving Group ◽  
Hydrolysis Of ◽  
Equilibrium Binding Constant

The pH-dependence of the Michaelis–Menten parameters for the papain-catalysed hydrolysis of N-acetyl-l-phenylalanylglycine p-nitroanilide was determined. The equilibrium binding constant, Ks, is independent of pH between 3.7 and 9.3, whereas the acylation constant, k+2, shows bell-shaped pH-dependence with apparent pKa values of 4.2 and 8.2. The effect of substituents in the leaving group on the acylation constant of the papain-catalysed hydrolysis of hippuryl anilides and N-acetyl-l-phenylalanylglycine anilides gives rise in both series to a Hammett ρ value of -1.04. This indicates that the enzyme provides electrophilic, probably general-acid, catalysis, as well as the nucleophilic or general-base catalysis previously found. A mechanism involving a tetrahedral intermediate whose formation is general-base-catalysed and whose breakdown is general-acid-catalysed seems most likely. The similarity of the Hammett ρ values appears to exclude facilitated proton transfer as a means through which the specificity of papain is expressed.

scholarly journals Mechanisms of RNA catalysis

2011 ◽  
Vol 366 (1580) ◽  
pp. 2910-2917 ◽  
Author(s):  
David M. J. Lilley
Keyword(s):  
Distinct Species ◽  
Base Catalysis ◽  
Nucleophilic Attack ◽  
Phosphoryl Transfer ◽  
Rna Catalysis ◽  
Rna Molecules ◽  
General Base ◽  
General Acid ◽  
Guanine And Adenine ◽  
Self Splicing

Ribozymes are RNA molecules that act as chemical catalysts. In contemporary cells, most known ribozymes carry out phosphoryl transfer reactions. The nucleolytic ribozymes comprise a class of five structurally-distinct species that bring about site-specific cleavage by nucleophilic attack of the 2′-O on the adjacent 3′-P to form a cyclic 2′,3′-phosphate. In general, they will also catalyse the reverse reaction. As a class, all these ribozymes appear to use general acid–base catalysis to accelerate these reactions by about a million-fold. In the Varkud satellite ribozyme, we have shown that the cleavage reaction is catalysed by guanine and adenine nucleobases acting as general base and acid, respectively. The hairpin ribozyme most probably uses a closely similar mechanism. Guanine nucleobases appear to be a common choice of general base, but the general acid is more variable. By contrast, the larger ribozymes such as the self-splicing introns and RNase P act as metalloenzymes.

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