1t2c: Difference between revisions

Revision as of 19:07, 28 July 2008

This article has been automatically seeded. Changes to this page should pertain to the PDB entry only and not to the protein or biomolecule in general.

File:1t2c.png

Template:STRUCTURE 1t2c

Plasmodium falciparum lactate dehydrogenase complexed with NADHPlasmodium falciparum lactate dehydrogenase complexed with NADH

Template:ABSTRACT PUBMED 15117937

About this StructureAbout this Structure

1T2C is a Single protein structure of sequence from Plasmodium falciparum. Full crystallographic information is available from OCA.

ReferenceReference

Identification and activity of a series of azole-based compounds with lactate dehydrogenase-directed anti-malarial activity., Cameron A, Read J, Tranter R, Winter VJ, Sessions RB, Brady RL, Vivas L, Easton A, Kendrick H, Croft SL, Barros D, Lavandera JL, Martin JJ, Risco F, Garcia-Ochoa S, Gamo FJ, Sanz L, Leon L, Ruiz JR, Gabarro R, Mallo A, Gomez de las Heras F, J Biol Chem. 2004 Jul 23;279(30):31429-39. Epub 2004 Apr 26. PMID:15117937

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Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)

OCA

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-'''Plasmodium falciparum lactate dehydrogenase complexed with NADH'''
+===Plasmodium falciparum lactate dehydrogenase complexed with NADH===
-==Overview==
+<!--
-Plasmodium falciparum, the causative agent of malaria, relies extensively on glycolysis coupled with homolactic fermentation during its blood-borne stages for energy production. Selective inhibitors of the parasite lactate dehydrogenase (LDH), central to NAD(+) regeneration, therefore potentially provide a route to new antimalarial drugs directed against a novel molecular target. A series of heterocyclic, azole-based compounds are described that preferentially inhibit P. falciparum LDH at sub-micromolar concentrations, typically at concentrations about 100-fold lower than required for human lactate dehydrogenase inhibition. Crystal structures show these competitive inhibitors form a network of interactions with amino acids within the active site of the enzyme, stacking alongside the nicotinamide ring of the NAD(+) cofactor. These compounds display modest activity against parasitized erythrocytes, including parasite strains with known resistance to existing anti-malarials and against Plasmodium berghei in BALB/c mice. Initial toxicity data suggest the azole derivatives have generally low cytotoxicity, and preliminary pharmoco-kinetic data show favorable bioavailability and circulation times. These encouraging results suggest that further enhancement of these structures may yield candidates suitable for consideration as new therapeutics for the treatment of malaria. In combination these studies also provide strong support for the validity of targeting the Plasmodium glycolytic pathway and, in particular, LDH in the search for novel anti-malarials.
+The line below this paragraph, {{ABSTRACT_PUBMED_15117937}}, adds the Publication Abstract to the page
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+{{ABSTRACT_PUBMED_15117937}}
 ==About this Structure==
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 [[Category: Winter, V J.]]
 [[Category: Binary complex]]
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