2bla: Difference between revisions
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==SP21 double mutant P. vivax Dihydrofolate reductase in complex with pyrimethamine== | ==SP21 double mutant P. vivax Dihydrofolate reductase in complex with pyrimethamine== | ||
<StructureSection load='2bla' size='340' side='right' caption='[[2bla]], [[Resolution|resolution]] 2.50Å' scene=''> | <StructureSection load='2bla' size='340' side='right'caption='[[2bla]], [[Resolution|resolution]] 2.50Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[2bla]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Plavi Plavi]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2BLA OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2BLA FirstGlance]. <br> | <table><tr><td colspan='2'>[[2bla]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Plavi Plavi]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2BLA OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2BLA FirstGlance]. <br> | ||
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Check<jmol> | Check<jmol> | ||
<jmolCheckbox> | <jmolCheckbox> | ||
<scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/bl/2bla_consurf.spt"</scriptWhenChecked> | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/bl/2bla_consurf.spt"</scriptWhenChecked> | ||
<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> | ||
<text>to colour the structure by Evolutionary Conservation</text> | <text>to colour the structure by Evolutionary Conservation</text> | ||
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</div> | </div> | ||
<div class="pdbe-citations 2bla" style="background-color:#fffaf0;"></div> | <div class="pdbe-citations 2bla" style="background-color:#fffaf0;"></div> | ||
==See Also== | |||
*[[Dihydrofolate reductase 3D structures|Dihydrofolate reductase 3D structures]] | |||
== References == | == References == | ||
<references/> | <references/> | ||
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</StructureSection> | </StructureSection> | ||
[[Category: Dihydrofolate reductase]] | [[Category: Dihydrofolate reductase]] | ||
[[Category: Large Structures]] | |||
[[Category: Plavi]] | [[Category: Plavi]] | ||
[[Category: Chitnumsub, P]] | [[Category: Chitnumsub, P]] | ||
Revision as of 10:19, 21 August 2019
SP21 double mutant P. vivax Dihydrofolate reductase in complex with pyrimethamineSP21 double mutant P. vivax Dihydrofolate reductase in complex with pyrimethamine
Structural highlights
Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedPyrimethamine (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. 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[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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