Methylene tetrahydrofolate reductase (MTHFR) is an enzyme involved in the metabolism of homocysteine to methionine, and folic acid is an essential cofactor. Mutations in the MTHFR gene lead to hyperhomocysteinemia and vascular thrombosis. Heterozygous mutation involving a single nucleotide polymorphism in the MTHFR gene leading to vascular thrombosis is very rare. We present a case of segmental...

The pugilist-Dominantmutation results from fusion of a portion of the gene encoding the trifunctional Methylene Tetrahydrofolate Dehydrogenase (E.C.1.5.1.5, E.C.3.5.4.9, E.C.6.3.4.3) to approximately one kb of a heterochromatic satellite repeat. Expression of this fusion gene results in an unusual ring pattern of pigmentation around the eye. We carried out experiments to determine the mechanism...

19F-n.m.r. spectroscopy was used to study the binding of 3',5'-difluoromethotrexate to dihydrofolate reductase (tetrahydrofolate dehydrogenase) from Lactobacillus casei. The benzoyl ring of the bound difluoromethotrexate was found to 'flip' about its symmetry axis, and the rate (7.3 x 10s3-1 at 298 K) and activation parameters for this process were determined by lineshape analysis ofthe 19F-n.m...

BACKGROUND When organisms experience environmental change, how does their metabolic network reset and adapt to the new condition? Methylobacterium extorquens is a bacterium capable of growth on both multi- and single-carbon compounds. These different modes of growth utilize dramatically different central metabolic pathways with limited pathway overlap. METHODOLOGY/PRINCIPAL FINDINGS This stud...

In prokaryotes, PurU (10-formyl tetrahydrofolate [THF] deformylase) metabolizes 10-formyl THF to formate and THF for purine and Gly biosyntheses. The Arabidopsis thaliana genome contains two putative purU genes, At4g17360 and At5g47435. Knocking out these genes simultaneously results in plants that are smaller and paler than the wild type. These double knockout (dKO) mutant plants show a 70-fol...

Escherichia coli dihydrofolate reductase (DHFR) catalyzes the reduction of dihydrofolate to tetrahydrofolate. During the catalytic cycle, DHFR undergoes conformational transitions between the closed (CS) and occluded (OS) states that, respectively, describe whether the active site is closed or occluded by the Met20 loop. The CS-->OS and the reverse transition may be viewed as allosteric transit...