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Structures of the hydrolase domain of human 10-formyltetrahydrofolate dehydrogenase and its complex with a substrate analogue
- Source :
- Acta crystallographica. Section D, Biological crystallography. 62(Pt 11)
- Publication Year :
- 2006
-
Abstract
- 10-Formyltetrahydrofolate dehydrogenase is a ubiquitously expressed enzyme in the human body. It catalyses the formation of tetrahydrofolate and carbon dioxide from 10-­formyltetrahydrofolate, thereby playing an important role in the human metabolism of one-carbon units. It is a two-domain protein in which the N-terminal domain hydrolyses 10-formyltetrahydrofolate into formate and tetrahydrofolate. The high-resolution crystal structure of the hydrolase domain from human 10-formyltetrahydrofolate dehydrogenase has been determined in the presence and absence of a substrate analogue. The structures reveal conformational changes of two loops upon ligand binding, while key active-site residues appear to be pre-organized for catalysis prior to substrate binding. Two water molecules in the structures mark the positions of key oxygen moieties in the catalytic reaction and reaction geometries are proposed based on the structural data.
- Subjects :
- chemistry.chemical_classification
Oxidoreductases Acting on CH-NH Group Donors
Binding Sites
Formates
Stereochemistry
Leucovorin
Substrate (chemistry)
Dehydrogenase
General Medicine
Crystallography, X-Ray
Catalysis
Protein Structure, Secondary
Protein Structure, Tertiary
chemistry.chemical_compound
Protein structure
Enzyme
chemistry
Structural Biology
Oxidoreductase
Hydrolase
Humans
Formate
Binding site
Tetrahydrofolates
Subjects
Details
- ISSN :
- 09074449
- Volume :
- 62
- Issue :
- Pt 11
- Database :
- OpenAIRE
- Journal :
- Acta crystallographica. Section D, Biological crystallography
- Accession number :
- edsair.doi.dedup.....5f87cf2c21742f6040e531b274d2446f