Crystal structure of bifunctional 5,10-methylenetetrahydrofolate dehydrogenase/cyclohydrolase from Thermoplasma acidophilum

Won Ho Lee; Min Woo Sung; Jae Hee Kim; Young Kwan Kim; Arum Han; Kwang Yeon Hwang

doi:10.1016/j.bbrc.2011.02.074

Crystal structure of bifunctional 5,10-methylenetetrahydrofolate dehydrogenase/cyclohydrolase from Thermoplasma acidophilum

Won Ho Lee, Min Woo Sung, Jae Hee Kim, Young Kwan Kim, Arum Han, Kwang Yeon Hwang

Department of Biosystems and Biotechnology

Research output: Contribution to journal › Article › peer-review

5 Citations (Scopus)

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.

Original language	English
Pages (from-to)	459-463
Number of pages	5
Journal	Biochemical and biophysical research communications
Volume	406
Issue number	3
DOIs	https://doi.org/10.1016/j.bbrc.2011.02.074
Publication status	Published - 2011 Mar 18

Bibliographical note

Funding 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 .

Keywords

5,10-Methylenetetrahydrofolate dehydrogenase/cyclohydrolase
Folate
NADP complex structure
One-carbon metabolism
Tetrahydrofolate pathway

ASJC Scopus subject areas

Biophysics
Biochemistry
Molecular Biology
Cell Biology

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10.1016/j.bbrc.2011.02.074

Cite this

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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.",

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note = "Funding 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 .",

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AU - Kim, Young Kwan

AU - Han, Arum

AU - Hwang, Kwang Yeon

N1 - Funding 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 .

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N2 - 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.

AB - 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.

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Crystal structure of bifunctional 5,10-methylenetetrahydrofolate dehydrogenase/cyclohydrolase from Thermoplasma acidophilum

Abstract

Bibliographical note

Keywords

ASJC Scopus subject areas

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