4a26: Difference between revisions
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[[ | ==The crystal structure of Leishmania major N5,N10- methylenetetrahydrofolate dehydrogenase/cyclohydrolase== | ||
<StructureSection load='4a26' size='340' side='right' caption='[[4a26]], [[Resolution|resolution]] 2.70Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[4a26]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Leishmania_major Leishmania major]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4A26 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4A26 FirstGlance]. <br> | |||
</td></tr><tr><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene><br> | |||
<tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4a26 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4a26 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4a26 RCSB], [http://www.ebi.ac.uk/pdbsum/4a26 PDBsum]</span></td></tr> | |||
<table> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
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 2.7A 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. | |||
The crystal structure of Leishmania major N(5),N(10)-methylenetetrahydrofolate dehydrogenase/cyclohydrolase and assessment of a potential drug target.,Eadsforth TC, Cameron S, Hunter WN Mol Biochem Parasitol. 2012 Feb;181(2):178-85. Epub 2011 Nov 15. PMID:22108435<ref>PMID:22108435</ref> | |||
The | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
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< | |||
[[Category: Leishmania major]] | [[Category: Leishmania major]] | ||
[[Category: Cameron, S.]] | [[Category: Cameron, S.]] | ||
Revision as of 10:53, 5 June 2014
The crystal structure of Leishmania major N5,N10- methylenetetrahydrofolate dehydrogenase/cyclohydrolaseThe crystal structure of Leishmania major N5,N10- methylenetetrahydrofolate dehydrogenase/cyclohydrolase
Structural highlights
Publication Abstract from PubMedThree 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 2.7A 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. The crystal structure of Leishmania major N(5),N(10)-methylenetetrahydrofolate dehydrogenase/cyclohydrolase and assessment of a potential drug target.,Eadsforth TC, Cameron S, Hunter WN Mol Biochem Parasitol. 2012 Feb;181(2):178-85. Epub 2011 Nov 15. PMID:22108435[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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