2a94: Difference between revisions

Revision as of 18:45, 3 May 2008

Structure of Plasmodium falciparum lactate dehydrogenase complexed to APADH.

OverviewOverview

Malaria caused by Plasmodium vivax is a major cause of global morbidity and, in rare cases, mortality. Lactate dehydrogenase is an essential Plasmodium protein and, therefore, a potential antimalarial drug target. Ideally, drugs directed against this target would be effective against both major species of Plasmodium, P. falciparum and P. vivax. In this study, the crystal structure of the lactate dehydrogenase protein from P. vivax has been solved and is compared to the equivalent structure from the P. falciparum enzyme. The active sites and cofactor binding pockets of both enzymes are found to be highly similar and differentiate these enzymes from their human counterparts. These structures suggest effective inhibition of both enzymes should be readily achievable with a common inhibitor. The crystal structures of both enzymes have also been solved in complex with the synthetic cofactor APADH. The unusual cofactor binding site in these Plasmodium enzymes is found to readily accommodate both NADH and APADH, explaining why the Plasmodium enzymes retain enzymatic activity in the presence of this synthetic cofactor.

About this StructureAbout this Structure

2A94 is a Single protein structure of sequence from Plasmodium falciparum. Full crystallographic information is available from OCA.

ReferenceReference

Structure of lactate dehydrogenase from Plasmodium vivax: complexes with NADH and APADH., Chaikuad A, Fairweather V, Conners R, Joseph-Horne T, Turgut-Balik D, Brady RL, Biochemistry. 2005 Dec 13;44(49):16221-8. PMID:16331982 Page seeded by OCA on Sat May 3 18:45:57 2008

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OCA

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 [[Image:2a94.gif|left|200px]]
- {{Structure
+<!--
-|PDB= 2a94 |SIZE=350|CAPTION= <scene name='initialview01'>2a94</scene>, resolution 1.500&Aring;
+The line below this paragraph, containing "STRUCTURE_2a94", creates the "Structure Box" on the page.
-|SITE=
+You may change the PDB parameter (which sets the PDB file loaded into the applet)
-|LIGAND= <scene name='pdbligand=AP0:ACETYL+PYRIDINE+ADENINE+DINUCLEOTIDE,+REDUCED'>AP0</scene>
+or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
-|ACTIVITY= <span class='plainlinks'>[http://en.wikipedia.org/wiki/L-lactate_dehydrogenase L-lactate dehydrogenase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.1.1.27 1.1.1.27] </span>
+or leave the SCENE parameter empty for the default display.
-|GENE= LDH ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=5833 Plasmodium falciparum])
+-->
-|DOMAIN=
+{{STRUCTURE_2a94|  PDB=2a94  |  SCENE=  }}
-|RELATEDENTRY=
-|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2a94 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2a94 OCA], [http://www.ebi.ac.uk/pdbsum/2a94 PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=2a94 RCSB]</span>
-}}
 '''Structure of Plasmodium falciparum lactate dehydrogenase complexed to APADH.'''
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 [[Category: Joseph-Horne, T.]]
 [[Category: Turgut-Balik, D.]]
-[[Category: rossmann fold]]
+[[Category: Rossmann fold]]
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May  3 18:45:57 2008''
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 01:49:31 2008''