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Design of transition‐state analogues for gaba‐transaminase
Author(s) -
Andrews P. R.,
Iskander M. N.,
Jones G. P.,
Winkler D. A.
Publication year - 2009
Publication title -
international journal of quantum chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.484
H-Index - 105
eISSN - 1097-461X
pISSN - 0020-7608
DOI - 10.1002/qua.560220732
Subject(s) - gaba transaminase , chemistry , active site , catalysis , transition state , transaminase , transition state analog , enzyme , computational chemistry , transition (genetics) , stereochemistry , combinatorial chemistry , organic chemistry , biochemistry , gene , glutamate decarboxylase
Compounds which inhibit the mitochondrial enzyme GABA‐transaminase have considerable potential as anticonvulsant drugs. An approach which may provide potent and specific enzyme inhibitors involves the use of the transition‐state structure of the reaction catalyzed by the enzyme as a template for the design of transition‐state analogues. Molecular orbital calculations have been used to calculate the potential energy surface and identify the transition‐state structure for the reaction catalyzed by GABA‐transaminase. A series of transition‐state analogues based on this structure have been synthesized and were found to be biologically active. An active site model has also been developed on the basis of the calculated reaction pathway.