View source for 1t24


==Plasmodium falciparum lactate dehydrogenase complexed with NAD+ and 4-hydroxy-1,2,5-oxadiazole-3-carboxylic acid==
<StructureSection load='1t24' size='340' side='right'caption='[[1t24]], [[Resolution|resolution]] 1.70&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[1t24]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Plasmodium_falciparum Plasmodium falciparum]. The June 2008 RCSB PDB [https://pdb.rcsb.org/pdb/static.do?p=education_discussion/molecule_of_the_month/index.html Molecule of the Month] feature on ''Lactate Dehydrogenase''  by David S. Goodsell is [https://dx.doi.org/10.2210/rcsb_pdb/mom_2008_6 10.2210/rcsb_pdb/mom_2008_6]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1T24 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1T24 FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.7&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=NAD:NICOTINAMIDE-ADENINE-DINUCLEOTIDE'>NAD</scene>, <scene name='pdbligand=OXQ:4-HYDROXY-1,2,5-OXADIAZOLE-3-CARBOXYLIC+ACID'>OXQ</scene></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1t24 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1t24 OCA], [https://pdbe.org/1t24 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1t24 RCSB], [https://www.ebi.ac.uk/pdbsum/1t24 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1t24 ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/LDH_PLAFD LDH_PLAFD] 
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
Check<jmol>
  <jmolCheckbox>
    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/t2/1t24_consurf.spt"</scriptWhenChecked>
    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
    <text>to colour the structure by Evolutionary Conservation</text>
  </jmolCheckbox>
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=1t24 ConSurf].
<div style="clear:both"></div>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
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.

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<ref>PMID:15117937</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 1t24" style="background-color:#fffaf0;"></div>

==See Also==
*[[Lactate dehydrogenase 3D structures|Lactate dehydrogenase 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Lactate Dehydrogenase]]
[[Category: Large Structures]]
[[Category: Plasmodium falciparum]]
[[Category: RCSB PDB Molecule of the Month]]
[[Category: Barros D]]
[[Category: Brady RL]]
[[Category: Cameron A]]
[[Category: Croft SL]]
[[Category: De Las Heras FG]]
[[Category: Easton A]]
[[Category: Gabarro R]]
[[Category: Gamo FJ]]
[[Category: Garcia-Ochoa S]]
[[Category: Kendrick H]]
[[Category: Lavandera JL]]
[[Category: Leon L]]
[[Category: Mallo A]]
[[Category: Martin JJ]]
[[Category: Read J]]
[[Category: Risco F]]
[[Category: Ruiz JR]]
[[Category: Sanz L]]
[[Category: Sessions RB]]
[[Category: Tranter R]]
[[Category: Vivas L]]
[[Category: Winter VJ]]