title: Crystal structure of bifunctional 5,10-methylenetetrahydrofolate dehydrogenase/cyclohydrolase from Thermoplasma acidophilum.
abstract: 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.
authors.affiliation: Division of Biotechnology, College of Life Sciences and Biotechnology, Korea University, Seoul 136-713, South Korea.
authors.forename: Won Ho
authors.initials: WH
authors.lastname: Lee
authors.forename: Min Woo
authors.initials: MW
authors.lastname: Sung
authors.forename: Jae Hee
authors.initials: JH
authors.lastname: Kim
authors.forename: Young Kwan
authors.initials: YK
authors.lastname: Kim
authors.forename: Arum
authors.initials: A
authors.lastname: Han
authors.forename: Kwang Yeon
authors.initials: KY
authors.lastname: Hwang
mesh_terms: D000595:Amino Acid Sequence; D001665:Binding Sites; D017124:Conserved Sequence; D003460:Crystallization; D018360:Crystallography, X-Ray; D045064:Methenyltetrahydrofolate Cyclohydrolase / Q000737:chemistry* / Q000235:genetics; D008969:Molecular Sequence Data; D009249:NADP / Q000737:chemistry; D055503:Protein Multimerization; D017433:Protein Structure, Secondary; D013763:Tetrahydrofolates / Q000737:chemistry; D013822:Thermoplasma / Q000201:enzymology*
chemical_list: D013763:Tetrahydrofolates; C030371:5,6,7,8-tetrahydrofolic acid; D009249:NADP; D045064:Methenyltetrahydrofolate Cyclohydrolase