6ECR

The human methylenetetrahydrofolate dehydrogenase/cyclohydrolase (FolD) complexed with NADP

6ECR の概要

• エントリーDOI: 10.2210/pdb6ecr/pdb
• 分子名称: methylenetetrahydrofolate dehydrogenase cyclohydrolase, NADP NICOTINAMIDE-ADENINE-DINUCLEOTIDE PHOSPHATE, ACETATE ION, ... (4 entities in total)
• 機能のキーワード: dehydrogenase, cyclohydrolase, bifunctional protein, oxidoreductase
• 由来する生物種: Homo sapiens (Human)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 65727.55

構造登録者

Bueno, R.V.,Dawson, A.,Hunter, W.N. (登録日: 2018-08-08, 公開日: 2019-03-27, 最終更新日: 2023-10-11)

主引用文献

Bueno, R.,Dawson, A.,Hunter, W.N.
An assessment of three human methylenetetrahydrofolate dehydrogenase/cyclohydrolase-ligand complexes following further refinement.
Acta Crystallogr F Struct Biol Commun, 75:148-152, 2019

PubMed Abstract: The enzymes involved in folate metabolism are key drug targets for cell-growth modulation, and accurate crystallographic structures provide templates to be exploited for structure-based ligand design. In this context, three ternary complex structures of human methylenetetrahydrofolate dehydrogenase/cyclohydrolase have been published [Schmidt et al. (2000), Biochemistry, 39, 6325-6335] and potentially represent starting points for the development of new antifolate inhibitors. However, an inspection of the models and the deposited data revealed deficiencies and raised questions about the validity of the structures. A number of inconsistencies relating to the publication were also identified. Additional refinement was carried out with the deposited data, seeking to improve the models and to then validate the complex structures or correct the record. In one case, the inclusion of the inhibitor in the structure was supported and alterations to the model allowed details of enzyme-ligand interactions to be described that had not previously been discussed. For one weak inhibitor, the data suggested that the ligand may adopt two poses in the binding site, both with few interactions with the enzyme. In the third case, that of a potent inhibitor, inconsistencies were noted in the assignment of the chemical structure and there was no evidence to support the inclusion of the ligand in the active site.

PubMed: 30839287
DOI: 10.1107/S2053230X18018083

実験手法

X-RAY DIFFRACTION (2.2 Å)