15574-38-6Relevant academic research and scientific papers
Evidence that a ' dynamic knockoutg' in Escherichia coli dihydrofolate reductase does not affect the chemical step of catalysis
Loveridge, E. Joel,Behiry, Enas M.,Guo, Jiannan,Allemann, Rudolf K.
, p. 292 - 297 (2012)
The question of whether protein motions play a role in the chemical step of enzymatic catalysis has generated much controversy in recent years. Debate has recently reignited over possible dynamic contributions to catalysis in dihydrofolate reductase, foll
Method for preparing L-5-calcium methyl tetrahydrofolate through enzymic method
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Page/Page column 5-8, (2019/05/04)
The invention belongs to the technical field of enzymatic synthesis, and relates to a method for preparing L-5-calcium methyl tetrahydrofolate through an enzymic method. The method comprises the following steps that 1, folic acid serves as the raw materia
Binding pocket alterations in dihydrofolate synthase confer resistance to para-aminosalicylic acid in clinical isolates of Mycobacterium tuberculosis
Zhao, Fei,Wang, Xu-De,Erber, Luke N.,Luo, Ming,Guo, Ai-Zhen,Yang, Shan-Shan,Gu, Jing,Turman, Breanna J.,Gao, Yun-Rong,Li, Dong-Fang,Cui, Zong-Qiang,Zhang, Zhi-Ping,Bi, Li-Jun,Baughn, Anthony D.,Zhang, Xian-En,Deng, Jiao-Yu
, p. 1479 - 1487 (2014/03/21)
The mechanistic basis for the resistance of Mycobacterium tuberculosis to para-aminosalicylic acid (PAS), an important agent in the treatment of multidrug-resistant tuberculosis, has yet to be fully defined. As a substrate analog of the folate precursor paraaminobenzoic acid, PAS is ultimately bioactivated to hydroxy dihydrofolate, which inhibits dihydrofolate reductase and disrupts the operation of folate-dependent metabolic pathways. As a result, the mutation of dihydrofolate synthase, an enzyme needed for the bioactivation of PAS, causes PAS resistance in M. tuberculosis strain H37Rv. Here, we demonstrate that various missense mutations within the coding sequence of the dihydropteroate (H2Pte) binding pocket of dihydrofolate synthase (FolC) confer PAS resistance in laboratory isolates of M. tuberculosis and Mycobacterium bovis. From a panel of 85 multidrug-resistant M. tuberculosis clinical isolates, 5 were found to harbor mutations in the folC gene within the H2Pte binding pocket, resulting in PAS resistance. While these alterations in the H2Pte binding pocket resulted in reduced dihydrofolate synthase activity, they also abolished the bioactivation of hydroxy dihydropteroate to hydroxy dihydrofolate. Consistent with this model for abolished bioactivation, the introduction of a wild-type copy of folC fully restored PAS susceptibility in folC mutant strains. Confirmation of this novel PAS resistance mechanism will be beneficial for the development of molecular method-based diagnostics for M. tuberculosis clinical isolates and for further defining the mode of action of this important tuberculosis drug. Copyright
ASYMMETRIC REDUCTION OF DIHYDROFOLATE USING DIHYDROFOLATE REDUCTASE AND CHIRAL BORON-CONTAINING COMPOUNDS
Rees, Lilias,Valente, Edward,Suckling, Colin J.,Wood, Hamish C. S.
, p. 117 - 136 (2007/10/02)
The reduction of dihydrofolic acid to chiral tetrahydrofolic acid has been investigated by enzymic and non-enzymic means.With dihydrofolate reductase from E.coli as catalyst and recycling systems for NADPH, up to 1 g of optically pure stable tetrahydrofolate derivatives was obtained.The technique makes the possibility of synthesising chiral 5-formyltetrahydrofolate (leucovorin) for use in cancer rescue therapy attainable.In contrast, although dihydrofolate was reduced by a number of chiral boranes and borates built from amino acids and amino alcohols, enantiomeric excesses were minimal.
