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]] 1.54&Aring;' scene=''>
<StructureSection load='4ixe' size='340' side='right' caption='[[4ixe]], [[Resolution|resolution]] 1.54&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[4ixe]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Pneumocystis_carinii Pneumocystis carinii]. 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>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=IXE:N~6~-METHYL-N~6~-(3,4,5-TRIFLUOROPHENYL)PYRIDO[2,3-D]PYRIMIDINE-2,4,6-TRIAMINE'>IXE</scene>, <scene name='pdbligand=NDP:NADPH+DIHYDRO-NICOTINAMIDE-ADENINE-DINUCLEOTIDE+PHOSPHATE'>NDP</scene></td></tr>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=IXE:N~6~-METHYL-N~6~-(3,4,5-TRIFLUOROPHENYL)PYRIDO[2,3-D]PYRIMIDINE-2,4,6-TRIAMINE'>IXE</scene>, <scene name='pdbligand=NDP:NADPH+DIHYDRO-NICOTINAMIDE-ADENINE-DINUCLEOTIDE+PHOSPHATE'>NDP</scene></td></tr>
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2cd4|2cd4]], [[4ixf|4ixf]], [[4ixg|4ixg]]</td></tr>
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2cd4|2cd4]], [[4ixf|4ixf]], [[4ixg|4ixg]]</td></tr>
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><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></td></tr>
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><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></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4ixe FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ixe OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4ixe RCSB], [http://www.ebi.ac.uk/pdbsum/4ixe PDBsum]</span></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4ixe FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ixe OCA], [http://pdbe.org/4ixe PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4ixe RCSB], [http://www.ebi.ac.uk/pdbsum/4ixe PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4ixe ProSAT]</span></td></tr>
</table>
</table>
== Function ==
== Function ==
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
</div>
<div class="pdbe-citations 4ixe" style="background-color:#fffaf0;"></div>


==See Also==
==See Also==
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</StructureSection>
</StructureSection>
[[Category: Dihydrofolate reductase]]
[[Category: Dihydrofolate reductase]]
[[Category: Pneumocystis carinii]]
[[Category: Pneca]]
[[Category: Cody, V]]
[[Category: Cody, V]]
[[Category: Dihydrofolate reductase inhibitor cofactor ternary complex]]
[[Category: Dihydrofolate reductase inhibitor cofactor ternary complex]]
[[Category: Oxidoreductase-inhibitor complex]]
[[Category: Oxidoreductase-inhibitor complex]]
[[Category: Reductase]]
[[Category: Reductase]]

Revision as of 06:47, 5 August 2016

pcDHFR-NADPH-270pcDHFR-NADPH-270

Structural highlights

4ixe is a 1 chain structure with sequence from Pneca. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:,
Activity:Dihydrofolate reductase, with EC number 1.5.1.3
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

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 PubMed

Opportunistic 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 Also

References

  1. Gangjee A, Namjoshi OA, Raghavan S, Queener SF, Kisliuk RL, Cody V. Design, synthesis and molecular modeling of novel pyrido[2,3-d]pyrimidine analogs as antifolates: Application of Buchwald-Hartwig aminations of heterocycles. J Med Chem. 2013 Apr 29. PMID:23627352 doi:10.1021/jm400086g

4ixe, resolution 1.54Å

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OCA