Mechanism of action of zinc proteinases: A MNDO/d/H study of alternative general-acid general-base catalytic pathways for carboxypeptidase-A

2002 ◽  
Vol 88 (1) ◽  
pp. 87-98 ◽  
Author(s):  
Alexandra Kilshtain-Vardi ◽  
Gil Shoham ◽  
Amiram Goldblum
Keyword(s):  
Mechanism Of Action ◽  
Carboxypeptidase A ◽  
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.

scholarly journals Mechanism of action of carboxypeptidase A in ester hydrolysis.

1976 ◽  
Vol 73 (11) ◽  
pp. 3882-3886 ◽  
Author(s):  
M. W. Makinen ◽  
K. Yammura ◽  
E. T. Kaiser
Keyword(s):  
Mechanism Of Action ◽  
Ester Hydrolysis ◽  
Carboxypeptidase A

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
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