From Proteopedia
(Difference between revisions)
proteopedia linkproteopedia link
|
|
| Line 1: |
Line 1: |
| - | [[Image:1xiv.gif|left|200px]] | + | {{Seed}} |
| | + | [[Image:1xiv.png|left|200px]] |
| | | | |
| | <!-- | | <!-- |
| Line 9: |
Line 10: |
| | {{STRUCTURE_1xiv| PDB=1xiv | SCENE= }} | | {{STRUCTURE_1xiv| PDB=1xiv | SCENE= }} |
| | | | |
| - | '''Plasmodium falciparum lactate dehydrogenase complexed with 2-({4-chloro-[hydroxy(methoxy)methyl]cyclohexyl}amino)ethane-1,1,2-triol'''
| + | ===Plasmodium falciparum lactate dehydrogenase complexed with 2-({4-chloro-[hydroxy(methoxy)methyl]cyclohexyl}amino)ethane-1,1,2-triol=== |
| | | | |
| | | | |
| - | ==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== | | ==About this Structure== |
| Line 30: |
Line 34: |
| | [[Category: Sessions, R B.]] | | [[Category: Sessions, R B.]] |
| | [[Category: Protein-ligand complex]] | | [[Category: Protein-ligand complex]] |
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 15:05:13 2008'' | + | |
| | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Tue Jul 29 02:16:24 2008'' |
Revision as of 23:16, 28 July 2008
Template:STRUCTURE 1xiv
Plasmodium falciparum lactate dehydrogenase complexed with 2-({4-chloro-[hydroxy(methoxy)methyl]cyclohexyl}amino)ethane-1,1,2-triol
Template:ABSTRACT PUBMED 15978953
About this Structure
1XIV is a Single protein structure of sequence from Plasmodium falciparum. Full crystallographic information is available from OCA.
Reference
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 02:16:24 2008
