View source for 3bmq


==Structure of Pteridine Reductase 1 (PTR1) from Trypanosoma brucei in ternary complex with cofactor (NADP+) and inhibitor (Compound AX5)==
<StructureSection load='3bmq' size='340' side='right'caption='[[3bmq]], [[Resolution|resolution]] 1.70&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[3bmq]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Trybb Trybb]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3BMQ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3BMQ FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=AX5:6-(BENZYLSULFANYL)PYRIMIDINE-2,4-DIAMINE'>AX5</scene>, <scene name='pdbligand=DTT:2,3-DIHYDROXY-1,4-DITHIOBUTANE'>DTT</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=NAP:NADP+NICOTINAMIDE-ADENINE-DINUCLEOTIDE+PHOSPHATE'>NAP</scene></td></tr>
<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=CSX:S-OXY+CYSTEINE'>CSX</scene></td></tr>
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[2c7v|2c7v]], [[3bmc|3bmc]], [[3bmd|3bmd]], [[3bme|3bme]], [[3bmf|3bmf]], [[3bmg|3bmg]], [[3bmh|3bmh]], [[3bmi|3bmi]], [[3bmj|3bmj]], [[3bmk|3bmk]], [[3bml|3bml]], [[3bmm|3bmm]], [[3bmn|3bmn]], [[3bmo|3bmo]], [[3bmr|3bmr]], [[3bms|3bms]], [[3bmt|3bmt]]</div></td></tr>
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">PTR1 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=5702 TRYBB])</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=3bmq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3bmq OCA], [https://pdbe.org/3bmq PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3bmq RCSB], [https://www.ebi.ac.uk/pdbsum/3bmq PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3bmq ProSAT]</span></td></tr>
</table>
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
Check<jmol>
  <jmolCheckbox>
    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/bm/3bmq_consurf.spt"</scriptWhenChecked>
    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
    <text>to colour the structure by Evolutionary Conservation</text>
  </jmolCheckbox>
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=3bmq ConSurf].
<div style="clear:both"></div>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Pteridine reductase (PTR1) is a target for drug development against Trypanosoma and Leishmania species, parasites that cause serious tropical diseases and for which therapies are inadequate. We adopted a structure-based approach to the design of novel PTR1 inhibitors based on three molecular scaffolds. A series of compounds, most newly synthesized, were identified as inhibitors with PTR1-species specific properties explained by structural differences between the T. brucei and L. major enzymes. The most potent inhibitors target T. brucei PTR1, and two compounds displayed antiparasite activity against the bloodstream form of the parasite. PTR1 contributes to antifolate drug resistance by providing a molecular bypass of dihydrofolate reductase (DHFR) inhibition. Therefore, combining PTR1 and DHFR inhibitors might improve therapeutic efficacy. We tested two new compounds with known DHFR inhibitors. A synergistic effect was observed for one particular combination highlighting the potential of such an approach for treatment of African sleeping sickness.

Structure-Based Design of Pteridine Reductase Inhibitors Targeting African Sleeping Sickness and the Leishmaniases.,Tulloch LB, Martini VP, Iulek J, Huggan JK, Lee JH, Gibson CL, Smith TK, Suckling CJ, Hunter WN J Med Chem. 2009 Nov 16. PMID:19916554<ref>PMID:19916554</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 3bmq" style="background-color:#fffaf0;"></div>

==See Also==
*[[Pteridine reductase|Pteridine reductase]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Trybb]]
[[Category: Hunter, W N]]
[[Category: Iulek, J]]
[[Category: Martini, V P]]
[[Category: Inhibitor]]
[[Category: Oxidoreductase]]
[[Category: Pteridine reductase]]
[[Category: Ptr1]]
[[Category: Short chain dehydrogenase]]
[[Category: Trypanosoma brucei]]