4ixe: Difference between revisions
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==pcDHFR-NADPH-270== | ==pcDHFR-NADPH-270== | ||
<StructureSection load='4ixe' size='340' side='right' caption='[[4ixe]], [[Resolution|resolution]] 1.54Å' scene=''> | <StructureSection load='4ixe' size='340' side='right'caption='[[4ixe]], [[Resolution|resolution]] 1.54Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[4ixe]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Pneca Pneca]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4IXE OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4IXE FirstGlance]. <br> | <table><tr><td colspan='2'>[[4ixe]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Pneca Pneca]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4IXE OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4IXE FirstGlance]. <br> | ||
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</div> | </div> | ||
<div class="pdbe-citations 4ixe" style="background-color:#fffaf0;"></div> | <div class="pdbe-citations 4ixe" 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: Pneca]] | [[Category: Pneca]] | ||
[[Category: Cody, V]] | [[Category: Cody, V]] | ||
Revision as of 08:33, 13 February 2020
pcDHFR-NADPH-270pcDHFR-NADPH-270
Structural highlights
Function[DYR_PNECA] Key enzyme in folate metabolism. Catalyzes an essential reaction for de novo glycine and purine synthesis, and for DNA precursor synthesis. Publication Abstract from PubMedOpportunistic infections caused by Pneumocystis jirovecii (P. jirovecii, pj), Toxoplasma gondii (T. gondii, tg) and Mycobacterium avium (M. avium, ma) are the principal causes of morbidity and mortality in patients with acquired immunodeficiency syndrome (AIDS). The absence of any animal models for human Pneumocystis jirovecii pneumonia and the lack of crystal structures of pjDHFR and tgDHFR make the design of inhibitors challenging. A novel series of pyrido[2,3-d]pyrimidines as selective and potent DHFR inhibitors against these opportunistic infections are presented. Buchwald-Hartwig coupling reaction of substituted anilines with pivaloyl protected 2,4-diamino-6-bromo-pyrido[2,3-d]pyrimidine was successfully explored to synthesize these analogs. Compound 26 was the most selective inhibitor with excellent potency against pjDHFR. Molecular modeling studies with a pjDHFR homology model explained the potency and selectivity of 26. Structural data are also reported for 26 with pcDHFR and 16 and 22 with variants of pcDHFR. Design, synthesis and molecular modeling of novel pyrido[2,3-d]pyrimidine analogs as antifolates: Application of Buchwald-Hartwig aminations of heterocycles.,Gangjee A, Namjoshi OA, Raghavan S, Queener SF, Kisliuk RL, Cody V J Med Chem. 2013 Apr 29. PMID:23627352[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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