3jq9

From Proteopedia

(Difference between revisions)
Jump to: navigation, search
Current revision (08:02, 6 September 2023) (edit) (undo)
 
(6 intermediate revisions not shown.)
Line 1: Line 1:
-
{{Seed}}
 
-
[[Image:3jq9.jpg|left|200px]]
 
-
<!--
+
==Crystal structure of pteridine reductase 1 (PTR1) from Trypanosoma brucei in ternary complex with cofactor (NADP+) and inhibitor 2-amino-6-(1,3-benzodioxol-5-yl)-4-oxo-4,7-dihydro-3H-pyrrolo[2,3-d]pyrimidine-5-carbonitrile (AX1)==
-
The line below this paragraph, containing "STRUCTURE_3jq9", creates the "Structure Box" on the page.
+
<StructureSection load='3jq9' size='340' side='right'caption='[[3jq9]], [[Resolution|resolution]] 2.30&Aring;' scene=''>
-
You may change the PDB parameter (which sets the PDB file loaded into the applet)
+
== Structural highlights ==
-
or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
+
<table><tr><td colspan='2'>[[3jq9]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Trypanosoma_brucei Trypanosoma brucei]. This structure supersedes the now removed PDB entry [http://oca.weizmann.ac.il/oca-bin/send-pdb?obs=1&id=3bml 3bml]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3JQ9 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3JQ9 FirstGlance]. <br>
-
or leave the SCENE parameter empty for the default display.
+
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.3&#8491;</td></tr>
-
-->
+
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=AX1:2-AMINO-6-(1,3-BENZODIOXOL-5-YL)-4-OXO-4,7-DIHYDRO-3H-PYRROLO[2,3-D]PYRIMIDINE-5-CARBONITRILE'>AX1</scene>, <scene name='pdbligand=CSX:S-OXY+CYSTEINE'>CSX</scene>, <scene name='pdbligand=NAP:NADP+NICOTINAMIDE-ADENINE-DINUCLEOTIDE+PHOSPHATE'>NAP</scene></td></tr>
-
{{STRUCTURE_3jq9| PDB=3jq9 | SCENE= }}
+
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3jq9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3jq9 OCA], [https://pdbe.org/3jq9 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3jq9 RCSB], [https://www.ebi.ac.uk/pdbsum/3jq9 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3jq9 ProSAT]</span></td></tr>
 +
</table>
 +
== Function ==
 +
[https://www.uniprot.org/uniprot/Q581W1_TRYB2 Q581W1_TRYB2]
 +
== 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/jq/3jq9_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=3jq9 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.
-
===Crystal structure of pteridine reductase 1 (PTR1) from Trypanosoma brucei in ternary complex with cofactor (NADP+) and inhibitor 2-amino-6-(1,3-benzodioxol-5-yl)-4-oxo-4,7-dihydro-3H-pyrrolo[2,3-d]pyrimidine-5-carbonitrile (AX1)===
+
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 3jq9" style="background-color:#fffaf0;"></div>
-
<!--
+
==See Also==
-
The line below this paragraph, {{ABSTRACT_PUBMED_19916554}}, adds the Publication Abstract to the page
+
*[[Pteridine reductase|Pteridine reductase]]
-
(as it appears on PubMed at http://www.pubmed.gov), where 19916554 is the PubMed ID number.
+
== References ==
-
-->
+
<references/>
-
{{ABSTRACT_PUBMED_19916554}}
+
__TOC__
-
 
+
</StructureSection>
-
==About this Structure==
+
[[Category: Large Structures]]
-
3JQ9 is a 4 chains structure of sequences from [http://en.wikipedia.org/wiki/Trypanosoma_brucei Trypanosoma brucei]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3JQ9 OCA].
+
-
 
+
-
==Reference==
+
-
<ref group="xtra">PMID:19916554</ref><references group="xtra"/>
+
-
[[Category: Pteridine reductase]]
+
[[Category: Trypanosoma brucei]]
[[Category: Trypanosoma brucei]]
-
[[Category: Hunter, W N.]]
+
[[Category: Hunter WN]]
-
[[Category: Tulloch, L B.]]
+
[[Category: Tulloch LB]]
-
[[Category: Inhibitor]]
+
-
[[Category: Oxidoreductase]]
+
-
[[Category: Pteridine reductase]]
+
-
[[Category: Ptr1]]
+
-
[[Category: Short chain dehydrogenase]]
+
-
[[Category: Trypanosoma brucei]]
+
-
 
+
-
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Dec 9 15:14:09 2009''
+

Current revision

Crystal structure of pteridine reductase 1 (PTR1) from Trypanosoma brucei in ternary complex with cofactor (NADP+) and inhibitor 2-amino-6-(1,3-benzodioxol-5-yl)-4-oxo-4,7-dihydro-3H-pyrrolo[2,3-d]pyrimidine-5-carbonitrile (AX1)

PDB ID 3jq9

Drag the structure with the mouse to rotate

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/3jq9"
Personal tools