4A26

The crystal structure of Leishmania major N5,N10- methylenetetrahydrofolate dehydrogenase/cyclohydrolase

4A26 の概要

• エントリーDOI: 10.2210/pdb4a26/pdb
• 分子名称: PUTATIVE C-1-TETRAHYDROFOLATE SYNTHASE, CYTOPLASMIC, CHLORIDE ION (3 entities in total)
• 機能のキーワード: oxidoreductase, hydrolase, leishmaniasis
• 由来する生物種: LEISHMANIA MAJOR
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 64023.77

構造登録者

Eadsforth, T.C.,Cameron, S.,Hunter, W.N. (登録日: 2011-09-22, 公開日: 2011-10-26, 最終更新日: 2023-12-20)

主引用文献

Eadsforth, T.C.,Cameron, S.,Hunter, W.N.
The Crystal Structure of Leishmania Major N(5),N(10)-Methylenetetrahydrofolate Dehydrogenase/Cyclohydrolase and Assessment of a Potential Drug Target.
Mol.Biochem.Parasitol., 181:178-, 2012

PubMed Abstract: Three enzyme activities in the protozoan Leishmania major, namely N(5),N(10)-methylenetetrahydrofolate dehydrogenase/N(5),N(10)-methenyltetrahydrofolate cyclohydrolase (DHCH) and N(10)-formyltetrahydrofolate ligase (FTL) produce the essential intermediate N(10)-formyltetrahydrofolate. Although trypanosomatids possess at least one functional DHCH, the same is not true for FTL, which is absent in Trypanosoma brucei. Here, we present the 2.7 Å resolution crystal structure of the bifunctional apo-DHCH from L. major, which is a potential drug target. Sequence alignments show that the cytosolic enzymes found in trypanosomatids share a high level of identity of approximately 60%. Additionally, residues that interact and participate in catalysis in the human homologue are conserved amongst trypanosomatid sequences and this may complicate attempts to derive potent, parasite specific DHCH inhibitors.

PubMed: 22108435
DOI: 10.1016/J.MOLBIOPARA.2011.11.004

実験手法

X-RAY DIFFRACTION (2.7 Å)