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Postepy Biochem ; 61(3): 274-83, 2015.
Artigo em Polonês | MEDLINE | ID: mdl-26677574

RESUMO

Thymidylate synthase ThyA (EC 2.1.1.45;-encoded by the Tyms gene), having been for 60 years a molecular target in chemotherapy, catalyses the dUMP pyrimidine ring C(5) methylation reaction, encompassing a transfer of one-carbon group (the methylene one, thus at the formaldehyde oxidation level) from 6R-N5,10-methylenetetrahydrofolate, coupled with a reduction of this group to the methyl one, with concomitant generation of 7,8-dihydrofolate and thymidylate. New facts are presented, concerning (i) molecular mechanism of the catalyzed reaction, including the substrate selectivity mechanism, (ii) mechanism of inhibition by a particular inhibitor, N4-hydroxy-dCMP, (iii) structural properties of the enzyme, (iv) cellular localization, (v) potential posttranslational modifications of the enzyme protein and their influence on the catalytic properties and (vi) non-catalytic activities of the enzyme.


Assuntos
Bioquímica/história , Timidilato Sintase/história , Animais , Inibidores Enzimáticos/história , Inibidores Enzimáticos/farmacologia , História do Século XX , História do Século XXI , Humanos , Cinética , Polônia , Conformação Proteica , Processamento de Proteína Pós-Traducional , Especificidade por Substrato , Timidilato Sintase/antagonistas & inibidores , Timidilato Sintase/metabolismo
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