Projects per year
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 angstrom 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. (C) 2011 Elsevier B.V. All rights reserved.
Original language | English |
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Pages (from-to) | 178-185 |
Number of pages | 8 |
Journal | Molecular and Biochemical Parasitology |
Volume | 181 |
Issue number | 2 |
DOIs | |
Publication status | Published - Feb 2012 |
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Dive into the research topics of 'The crystal structure of Leishmania major N-5,N-10-methylenetetrahydrofolate dehydrogenase/cyclohydrolase and assessment of a potential drug target'. Together they form a unique fingerprint.Projects
- 2 Finished
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Aref#d: 19815. Wellcome Trust Centre for Drug Discovery (Strategic Award)
Fairlamb, A. (Investigator), Ferguson, M. (Investigator) & Frearson, J. (Investigator)
1/01/08 → 31/12/12
Project: Research
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Aref#d: 19401. Structure, specificity and mechanism of biosynthetic enzymes in trypanosomatids and inhibitor discovery of essential microbial functions (Programme Grant)
Hunter, B. (Investigator)
1/11/07 → 31/12/13
Project: Research