Folate co-enzymes play a pivotal role in one-carbon transfer cellular processes. Many eukaryotes encode the tri-functional tetrahydrofolate dehydrogenase/cyclohydrolase/synthetase (deh/cyc/syn) enzyme, which consists of a N-terminal bifunctional domain (deh/cyc) and a C-terminal monofunctional domain (syn). Here, we report the first analogous archeal enzyme structures, for the bifunctional methylenetetrahydrofolate dehydrogenase/cyclohydrolase from Thermoplasma acidophilum (TaMTHFDC) as the native protein and also as its NADP complex. The TaMTHFDC structure is a dimer with a polar interface, as well as a NADP binding site that shows minor conformational change. The orientations of the residues in the NADP binding site do not change on ligand binding, incorporating three water molecules which are hydrogen bonded with phosphate groups of NADP in the structure of the complex. Our structural information will contribute to an improved understanding of the basis of THF and one-carbon metabolism.
|Number of pages||5|
|Journal||Biochemical and biophysical research communications|
|Publication status||Published - 2011 Mar 18|
Bibliographical noteFunding Information:
We are grateful to Dr. H.S. Lee and his staff at the Pohang Light Source (PLS), beamline 4A, South Korea, for their assistance in this study. This study was supported by a grant from the National R&D Program for Cancer Control, Ministry for Health and Welfare, Republic of Korea ( 0720160 ); the Functional Proteomics Center, 21C Frontier Program, of the Korea Ministry of Science and Technology and World-Class University Project (R33-10108). A. Han, H.S. Kim were supported by a Brain Korea 21 research fellowship .
- 5,10-Methylenetetrahydrofolate dehydrogenase/cyclohydrolase
- NADP complex structure
- One-carbon metabolism
- Tetrahydrofolate pathway
ASJC Scopus subject areas
- Molecular Biology
- Cell Biology