4A26

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

Summary for 4A26

• Entry DOI: 10.2210/pdb4a26/pdb
• Descriptor: PUTATIVE C-1-TETRAHYDROFOLATE SYNTHASE, CYTOPLASMIC, CHLORIDE ION (3 entities in total)
• Functional Keywords: oxidoreductase, hydrolase, leishmaniasis
• Biological source: LEISHMANIA MAJOR
• Total number of polymer chains: 2
• Total formula weight: 64023.77

Authors

Eadsforth, T.C.,Cameron, S.,Hunter, W.N. (deposition date: 2011-09-22, release date: 2011-10-26, Last modification date: 2023-12-20)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (2.7 Å)