2bl9

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[[Image:2bl9.gif|left|200px]]
[[Image:2bl9.gif|left|200px]]
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{{Structure
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<!--
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|PDB= 2bl9 |SIZE=350|CAPTION= <scene name='initialview01'>2bl9</scene>, resolution 1.90&Aring;
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The line below this paragraph, containing "STRUCTURE_2bl9", creates the "Structure Box" on the page.
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|SITE= <scene name='pdbsite=AC1:Cp6+Binding+Site+For+Chain+A'>AC1</scene>
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You may change the PDB parameter (which sets the PDB file loaded into the applet)
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|LIGAND= <scene name='pdbligand=CP6:5-(4-CHLORO-PHENYL)-6-ETHYL-PYRIMIDINE-2,4-DIAMINE'>CP6</scene>, <scene name='pdbligand=NDP:NADPH+DIHYDRO-NICOTINAMIDE-ADENINE-DINUCLEOTIDE+PHOSPHATE'>NDP</scene>
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or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
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|ACTIVITY= <span class='plainlinks'>[http://en.wikipedia.org/wiki/Dihydrofolate_reductase Dihydrofolate reductase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.5.1.3 1.5.1.3] </span>
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or leave the SCENE parameter empty for the default display.
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|GENE=
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-->
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|DOMAIN=
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{{STRUCTURE_2bl9| PDB=2bl9 | SCENE= }}
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|RELATEDENTRY=
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|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2bl9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2bl9 OCA], [http://www.ebi.ac.uk/pdbsum/2bl9 PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=2bl9 RCSB]</span>
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}}
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'''X-RAY CRYSTAL STRUCTURE OF PLASMODIUM VIVAX DIHYDROFOLATE REDUCTASE IN COMPLEX WITH PYRIMETHAMINE AND ITS DERIVATIVE'''
'''X-RAY CRYSTAL STRUCTURE OF PLASMODIUM VIVAX DIHYDROFOLATE REDUCTASE IN COMPLEX WITH PYRIMETHAMINE AND ITS DERIVATIVE'''
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[[Category: Walkinshaw, M D.]]
[[Category: Walkinshaw, M D.]]
[[Category: Yuthavong, Y.]]
[[Category: Yuthavong, Y.]]
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[[Category: dihydrofolate reductase]]
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[[Category: Dihydrofolate reductase]]
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[[Category: drug resistance]]
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[[Category: Drug resistance]]
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[[Category: malaria]]
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[[Category: Malaria]]
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[[Category: oxidoreductase]]
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[[Category: Oxidoreductase]]
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[[Category: plamodium vivax]]
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[[Category: Plamodium vivax]]
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[[Category: pyrimethamine]]
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[[Category: Pyrimethamine]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 20:26:49 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 02:08:04 2008''
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Revision as of 17:26, 3 May 2008

Image:2bl9.gif

Template:STRUCTURE 2bl9

X-RAY CRYSTAL STRUCTURE OF PLASMODIUM VIVAX DIHYDROFOLATE REDUCTASE IN COMPLEX WITH PYRIMETHAMINE AND ITS DERIVATIVE


Overview

Pyrimethamine (Pyr) targets dihydrofolate reductase of Plasmodium vivax (PvDHFR) as well as other malarial parasites, but its use as antimalarial is hampered by the widespread high resistance. Comparison of the crystal structures of PvDHFR from wild-type and the Pyr-resistant (SP21, Ser-58 --> Arg + Ser-117 --> Asn) strain as complexes with NADPH and Pyr or its analog lacking p-Cl (Pyr20) clearly shows that the steric conflict arising from the side chain of Asn-117 in the mutant enzyme, accompanied by the loss of binding to Ser-120, is mainly responsible for the reduction in binding of Pyr. Pyr20 still effectively inhibits both the wild-type and SP21 proteins, and the x-ray structures of these complexes show how Pyr20 fits into both active sites without steric strain. These structural insights suggest a general approach for developing new generations of antimalarial DHFR inhibitors that, by only occupying substrate space of the active site, would retain binding affinity with the mutant enzymes.

About this Structure

2BL9 is a Single protein structure of sequence from Plasmodium vivax. Full crystallographic information is available from OCA.

Reference

Crystal structure of dihydrofolate reductase from Plasmodium vivax: pyrimethamine displacement linked with mutation-induced resistance., Kongsaeree P, Khongsuk P, Leartsakulpanich U, Chitnumsub P, Tarnchompoo B, Walkinshaw MD, Yuthavong Y, Proc Natl Acad Sci U S A. 2005 Sep 13;102(37):13046-51. Epub 2005 Aug 31. PMID:16135570 Page seeded by OCA on Sat May 3 20:26:49 2008

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