1oc4

File:1oc4.gif

spinqualitylabelsall models 1oc4, resolution 2.30Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image

LACTATE DEHYDROGENASE FROM PLASMODIUM BERGHEI

OverviewOverview

As Plasmodium rely extensively on homolactic fermentation for energy, production, Plasmodium falciparum lactate dehydrogenase (PfLDH)--the key, enzyme in this process--has previously been suggested as a novel target, for antimalarials. This enzyme has distinctive kinetic and structural, properties that distinguish it from its human homologues. In this study, we now describe the expression, kinetic characterisation and crystal, structure determination of the LDH from Plasmodium berghei. This enzyme is, seen to have a similar kinetic profile to its P. falciparum counterpart, exhibiting the characteristic lack of substrate inhibition that, distinguishes plasmodial from human LDHs. The crystal structure of P., berghei lactate dehydrogenase (PbLDH) shows a very similar active site, arrangement to the P. falciparum enzyme. In particular, an insertion of, five amino acid residues in the active site loop creates an enlarged, volume in the substrate binding site, and characteristic changes in the, residues lining the NADH cofactor binding pocket result in displacement of, the cofactor relative to its observed position in mammalian and all other, LDH structures. These results imply the special features previously, described for PfLDH may be shared across the Plasmodium genus, supporting, the universal application of therapeutics targeting this enzyme.

About this StructureAbout this Structure

1OC4 is a Single protein structure of sequence from Plasmodium berghei with NAD, OXM and GOL as ligands. Active as L-lactate dehydrogenase, with EC number 1.1.1.27 Structure known Active Site: AC1. Full crystallographic information is available from OCA.

ReferenceReference

Crystal structure of Plasmodium berghei lactate dehydrogenase indicates the unique structural differences of these enzymes are shared across the Plasmodium genus., Winter VJ, Cameron A, Tranter R, Sessions RB, Brady RL, Mol Biochem Parasitol. 2003 Sep;131(1):1-10. PMID:12967707

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