2a92
From Proteopedia
(New page: 200px<br /><applet load="2a92" size="350" color="white" frame="true" align="right" spinBox="true" caption="2a92, resolution 2.040Å" /> '''Crystal structure o...) |
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==Overview== | ==Overview== | ||
| - | Malaria caused by Plasmodium vivax is a major cause of global morbidity | + | 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 Structure== | ==About this Structure== | ||
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[[Category: Plasmodium vivax]] | [[Category: Plasmodium vivax]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
| - | [[Category: Brady, R | + | [[Category: Brady, R L.]] |
[[Category: Chaikuad, A.]] | [[Category: Chaikuad, A.]] | ||
[[Category: Conners, R.]] | [[Category: Conners, R.]] | ||
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[[Category: rossmann fold]] | [[Category: rossmann fold]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 16:25:04 2008'' |
Revision as of 14:25, 21 February 2008
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Crystal structure of lactate dehydrogenase from Plasmodium vivax: complex with NADH
Overview
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 Structure
2A92 is a Single protein structure of sequence from Plasmodium vivax with as ligand. Active as L-lactate dehydrogenase, with EC number 1.1.1.27 Full crystallographic information is available from OCA.
Reference
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
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