3t70: Difference between revisions

Latest revision as of 17:29, 1 November 2023

5'-Diphenyl Nucleoside Inhibitors of Plasmodium falciparum dUTPase

Structural highlights

3t70 is a 4 chain structure with sequence from Plasmodium falciparum 3D7 and Synthetic construct. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 1.8Å
Ligands:	DU4, SO4
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

Q8II92_PLAF7

Publication Abstract from PubMed

Deoxyuridine 5'-triphosphate nucleotidohydrolase (dUTPase) is a potential drug target for malaria. We previously reported some 5'-tritylated deoxyuridine analogues (both cyclic and acyclic) as selective inhibitors of the Plasmodium falciparum dUTPase. Modelling studies indicated that it might be possible to replace the trityl group with a diphenyl moiety, as two of the phenyl groups are buried, whereas the third is exposed to solvent. Herein we report the synthesis and evaluation of some diphenyl analogues that have lower lipophilicity and molecular weight than the trityl lead compound. Co-crystal structures show that the diphenyl inhibitors bind in a similar manner to the corresponding trityl derivatives, with the two phenyl moieties occupying the predicted buried phenyl binding sites. The diphenyl compounds prepared show similar or slightly lower inhibition of PfdUTPase, and similar or weaker inhibition of parasite growth than the trityl compounds.

Design, synthesis, and evaluation of 5'-diphenyl nucleoside analogues as inhibitors of the Plasmodium falciparum dUTPase.,Hampton SE, Baragana B, Schipani A, Bosch-Navarrete C, Musso-Buendia JA, Recio E, Kaiser M, Whittingham JL, Roberts SM, Shevtsov M, Brannigan JA, Kahnberg P, Brun R, Wilson KS, Gonzalez-Pacanowska D, Johansson NG, Gilbert IH ChemMedChem. 2011 Oct 4;6(10):1816-31. PMID:22049550^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Hampton SE, Baragana B, Schipani A, Bosch-Navarrete C, Musso-Buendia JA, Recio E, Kaiser M, Whittingham JL, Roberts SM, Shevtsov M, Brannigan JA, Kahnberg P, Brun R, Wilson KS, Gonzalez-Pacanowska D, Johansson NG, Gilbert IH. Design, synthesis, and evaluation of 5'-diphenyl nucleoside analogues as inhibitors of the Plasmodium falciparum dUTPase. ChemMedChem. 2011 Oct 4;6(10):1816-31. PMID:22049550

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OCA

[1] Hampton SE, Baragana B, Schipani A, Bosch-Navarrete C, Musso-Buendia JA, Recio E, Kaiser M, Whittingham JL, Roberts SM, Shevtsov M, Brannigan JA, Kahnberg P, Brun R, Wilson KS, Gonzalez-Pacanowska D, Johansson NG, Gilbert IH. Design, synthesis, and evaluation of 5'-diphenyl nucleoside analogues as inhibitors of the Plasmodium falciparum dUTPase. ChemMedChem. 2011 Oct 4;6(10):1816-31. PMID:22049550

[1]

@@ Line 3: / Line 3: @@
 <StructureSection load='3t70' size='340' side='right'caption='[[3t70]], [[Resolution|resolution]] 1.80&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[3t70]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Plaf7 Plaf7]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3T70 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3T70 FirstGlance]. <br>
+<table><tr><td colspan='2'>[[3t70]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Plasmodium_falciparum_3D7 Plasmodium falciparum 3D7] and [https://en.wikipedia.org/wiki/Synthetic_construct Synthetic construct]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3T70 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3T70 FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=DU4:2,5-DIDEOXY-5-[(DIPHENYLMETHYL)(METHYL)AMINO]URIDINE'>DU4</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.8&#8491;</td></tr>
-<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[3t6y|3t6y]]</div></td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=DU4:2,5-DIDEOXY-5-[(DIPHENYLMETHYL)(METHYL)AMINO]URIDINE'>DU4</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
-<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">PF11_0282 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=36329 PLAF7])</td></tr>
-<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/dUTP_diphosphatase dUTP diphosphatase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.6.1.23 3.6.1.23] </span></td></tr>
 <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3t70 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3t70 OCA], [https://pdbe.org/3t70 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3t70 RCSB], [https://www.ebi.ac.uk/pdbsum/3t70 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3t70 ProSAT]</span></td></tr>
 </table>
+== Function ==
+[https://www.uniprot.org/uniprot/Q8II92_PLAF7 Q8II92_PLAF7]
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==
@@ Line 27: / Line 27: @@
 </StructureSection>
 [[Category: Large Structures]]
-[[Category: Plaf7]]
+[[Category: Plasmodium falciparum 3D7]]
-[[Category: DUTP diphosphatase]]
+[[Category: Synthetic construct]]
-[[Category: Baragana, B]]
+[[Category: Baragana B]]
-[[Category: Bosch-Navarrete, C]]
+[[Category: Bosch-Navarrete C]]
-[[Category: Brannigan, J A]]
+[[Category: Brannigan JA]]
-[[Category: Brun, R]]
+[[Category: Brun R]]
-[[Category: Gilbert, I H]]
+[[Category: Gilbert IH]]
-[[Category: Gonzalez-Pacanowska, D]]
+[[Category: Gonzalez-Pacanowska D]]
-[[Category: Hampton, S E]]
+[[Category: Hampton SE]]
-[[Category: Johansson, N G]]
+[[Category: Johansson NG]]
-[[Category: Kahnberg, P]]
+[[Category: Kahnberg P]]
-[[Category: Kaiser, M]]
+[[Category: Kaiser M]]
-[[Category: Musso-Buendia, A]]
+[[Category: Musso-Buendia A]]
-[[Category: Recio, E]]
+[[Category: Recio E]]
-[[Category: Roberts, S M]]
+[[Category: Roberts SM]]
-[[Category: Schipani, A]]
+[[Category: Schipani A]]
-[[Category: Shevtsov, M]]
+[[Category: Shevtsov M]]
-[[Category: Whittingham, J L]]
+[[Category: Whittingham JL]]
-[[Category: Wilson, K S]]
+[[Category: Wilson KS]]
-[[Category: Dutp binding]]
-[[Category: Hydrolase-hydrolase inhibitor complex]]
-[[Category: Nucleus]]

3t70: Difference between revisions

Latest revision as of 17:29, 1 November 2023

5'-Diphenyl Nucleoside Inhibitors of Plasmodium falciparum dUTPase

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

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