1u5c: Difference between revisions

Revision as of 09:04, 29 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:1u5c.png

Template:STRUCTURE 1u5c

Plasmodium falciparum lactate dehydrogenase complexed with 3,7-dihydroxynaphthalene-2-carboxylic acid and NAD+Plasmodium falciparum lactate dehydrogenase complexed with 3,7-dihydroxynaphthalene-2-carboxylic acid and NAD+

Template:ABSTRACT PUBMED 15978953

About this StructureAbout this Structure

1U5C is a Single protein structure of sequence from Plasmodium falciparum. Full crystallographic information is available from OCA.

ReferenceReference

Mapping the binding site for gossypol-like inhibitors of Plasmodium falciparum lactate dehydrogenase., Conners R, Schambach F, Read J, Cameron A, Sessions RB, Vivas L, Easton A, Croft SL, Brady RL, Mol Biochem Parasitol. 2005 Aug;142(2):137-48. Epub 2005 Apr 18. PMID:15978953

Page seeded by OCA on Tue Jul 29 09:04:15 2008

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 3,7-dihydroxynaphthalene-2-carboxylic acid and NAD+'''
+===Plasmodium falciparum lactate dehydrogenase complexed with 3,7-dihydroxynaphthalene-2-carboxylic acid and NAD+===
-==Overview==
+<!--
-Gossypol is a di-sesquiterpene natural-product in the form of a functionalised binaphthyl and is isolated from cotton plants. The compound has long been known to exhibit anti-malarial and other biological activities. Previous studies have indicated that compounds of this type target Plasmodium falciparum lactate dehydrogenase (pfLDH), an essential enzyme for energy generation within the parasite. In this study, we report that simple naphthalene-based compounds, the core of the gossypol structure, exhibit weak inhibition of the parasite lactate dehydrogenase. Crystal structures of the complexes formed by binding of these naphthalene-based compounds to their target enzyme have been used to delineate the molecular features likely to form the gossypol binding site. Two modes of binding are observed: one overlapping the pyruvate but not the co-factor site, the other bridging the binding sites for the co-factor nicontinamide group and pyruvate substrate. This latter site encompasses molecular features unique to Plasmodium forms of LDH and is likely to represent the mode of binding for gossypol derivatives that show selectivity for the parasite enzymes. We also report a substrate analogue that unexpectedly binds within the adenine pocket of the co-factor groove. Although these core pharmacophore-like molecules only exhibit low levels of inhibitory activity, these molecular snapshots provide a rational basis for renewed structure-based development of naphthalene-based compounds as anti-malarial agents.
+The line below this paragraph, {{ABSTRACT_PUBMED_15978953}}, adds the Publication Abstract to the page
+(as it appears on PubMed at http://www.pubmed.gov), where 15978953 is the PubMed ID number.
+-->
+{{ABSTRACT_PUBMED_15978953}}
 ==About this Structure==
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 [[Category: Sessions, R B.]]
 [[Category: Protein-ligand complex]]
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