1w0c: Difference between revisions

From Proteopedia
Jump to navigation Jump to search
New page: left|200px <!-- The line below this paragraph, containing "STRUCTURE_1w0c", creates the "Structure Box" on the page. You may change the PDB parameter (which sets the PD...
 
No edit summary
 
(8 intermediate revisions by the same user not shown)
Line 1: Line 1:
[[Image:1w0c.png|left|200px]]


<!--
==Inhibition of Leishmania major pteridine reductase (PTR1) by 2,4,6-triaminoquinazoline; structure of the NADP ternary complex.==
The line below this paragraph, containing "STRUCTURE_1w0c", creates the "Structure Box" on the page.
<StructureSection load='1w0c' size='340' side='right'caption='[[1w0c]], [[Resolution|resolution]] 2.60&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'>[[1w0c]] is a 8 chain structure with sequence from [https://en.wikipedia.org/wiki/Leishmania_major Leishmania major]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1W0C OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1W0C 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]] 2.6&#8491;</td></tr>
-->
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=NAP:NADP+NICOTINAMIDE-ADENINE-DINUCLEOTIDE+PHOSPHATE'>NAP</scene>, <scene name='pdbligand=TAQ:2,4,6-TRIAMINOQUINAZOLINE'>TAQ</scene></td></tr>
{{STRUCTURE_1w0c|  PDB=1w0c  |  SCENE=  }}
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1w0c FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1w0c OCA], [https://pdbe.org/1w0c PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1w0c RCSB], [https://www.ebi.ac.uk/pdbsum/1w0c PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1w0c ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/PTR1_LEIMA PTR1_LEIMA] Exhibits a NADPH-dependent biopterin reductase activity. Has good activity with folate and significant activity with dihydrofolate and dihydrobiopterin, but not with quinonoid dihydrobiopterin. Confers resistance to methotrexate (MTX).<ref>PMID:7972081</ref>
== 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/w0/1w0c_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=1w0c ConSurf].
<div style="clear:both"></div>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
The structure of Leishmania major pteridine reductase (PTR1) in complex with NADPH and the inhibitor 2,4,6-triaminoquinazoline (TAQ) has been solved in a new crystal form by molecular replacement and refined to 2.6 A resolution. The inhibitor mimics a fragment, the pterin head group, of the archetypal antifolate drug methotrexate (MTX) and exploits similar chemical features to bind in the PTR1 active site. Despite being a much smaller molecule, TAQ displays a similar inhibition constant to that of MTX. PTR1 is a target for the development of improved therapies for infections caused by trypanosomatid parasites and this analysis provides information to assist the structure-based development of novel enzyme inhibitors.


===INHIBITION OF LEISHMANIA MAJOR PTERIDINE REDUCTASE (PTR1) BY 2,4,6-TRIAMINOQUINAZOLINE; STRUCTURE OF THE NADP TERNARY COMPLEX.===
Inhibition of Leishmania major pteridine reductase by 2,4,6-triaminoquinazoline: structure of the NADPH ternary complex.,McLuskey K, Gibellini F, Carvalho P, Avery MA, Hunter WN Acta Crystallogr D Biol Crystallogr. 2004 Oct;60(Pt 10):1780-5. Epub 2004, Sep 23. PMID:15388924<ref>PMID:15388924</ref>


From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 1w0c" style="background-color:#fffaf0;"></div>


<!--
==See Also==
The line below this paragraph, {{ABSTRACT_PUBMED_15388924}}, adds the Publication Abstract to the page
*[[Pteridine reductase|Pteridine reductase]]
(as it appears on PubMed at http://www.pubmed.gov), where 15388924 is the PubMed ID number.
== References ==
-->
<references/>
{{ABSTRACT_PUBMED_15388924}}
__TOC__
 
</StructureSection>
==About this Structure==
[[Category: Large Structures]]
[[1w0c]] is a 8 chain structure with sequence from [http://en.wikipedia.org/wiki/Leishmania_major Leishmania major]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1W0C OCA].
 
==Reference==
<ref group="xtra">PMID:015388924</ref><references group="xtra"/>
[[Category: Leishmania major]]
[[Category: Leishmania major]]
[[Category: Pteridine reductase]]
[[Category: Avery M]]
[[Category: Avery, M.]]
[[Category: Carvalho P]]
[[Category: Carvalho, P.]]
[[Category: Gibellini F]]
[[Category: Gibellini, F.]]
[[Category: Hunter W]]
[[Category: Hunter, W.]]
[[Category: Mcluskey K]]
[[Category: Mcluskey, K.]]
[[Category: Enzyme inhibitor]]
[[Category: Leishmania]]
[[Category: Methotrexate]]
[[Category: Methotrexate resistance]]
[[Category: Nadp]]
[[Category: Oxidoreductase]]
[[Category: Pterin]]
[[Category: Short-chain reductase]]
[[Category: Trypanosoma]]

Latest revision as of 16:10, 13 December 2023

Inhibition of Leishmania major pteridine reductase (PTR1) by 2,4,6-triaminoquinazoline; structure of the NADP ternary complex.Inhibition of Leishmania major pteridine reductase (PTR1) by 2,4,6-triaminoquinazoline; structure of the NADP ternary complex.

Structural highlights

1w0c is a 8 chain structure with sequence from Leishmania major. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 2.6Å
Ligands:,
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

PTR1_LEIMA Exhibits a NADPH-dependent biopterin reductase activity. Has good activity with folate and significant activity with dihydrofolate and dihydrobiopterin, but not with quinonoid dihydrobiopterin. Confers resistance to methotrexate (MTX).[1]

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

Publication Abstract from PubMed

The structure of Leishmania major pteridine reductase (PTR1) in complex with NADPH and the inhibitor 2,4,6-triaminoquinazoline (TAQ) has been solved in a new crystal form by molecular replacement and refined to 2.6 A resolution. The inhibitor mimics a fragment, the pterin head group, of the archetypal antifolate drug methotrexate (MTX) and exploits similar chemical features to bind in the PTR1 active site. Despite being a much smaller molecule, TAQ displays a similar inhibition constant to that of MTX. PTR1 is a target for the development of improved therapies for infections caused by trypanosomatid parasites and this analysis provides information to assist the structure-based development of novel enzyme inhibitors.

Inhibition of Leishmania major pteridine reductase by 2,4,6-triaminoquinazoline: structure of the NADPH ternary complex.,McLuskey K, Gibellini F, Carvalho P, Avery MA, Hunter WN Acta Crystallogr D Biol Crystallogr. 2004 Oct;60(Pt 10):1780-5. Epub 2004, Sep 23. PMID:15388924[2]

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

See Also

References

  1. ↑ Bello AR, Nare B, Freedman D, Hardy L, Beverley SM. PTR1: a reductase mediating salvage of oxidized pteridines and methotrexate resistance in the protozoan parasite Leishmania major. Proc Natl Acad Sci U S A. 1994 Nov 22;91(24):11442-6. PMID:7972081
  2. ↑ McLuskey K, Gibellini F, Carvalho P, Avery MA, Hunter WN. Inhibition of Leishmania major pteridine reductase by 2,4,6-triaminoquinazoline: structure of the NADPH ternary complex. Acta Crystallogr D Biol Crystallogr. 2004 Oct;60(Pt 10):1780-5. Epub 2004, Sep 23. PMID:15388924 doi:10.1107/S0907444904018955

1w0c, resolution 2.60Å

Drag the structure with the mouse to rotate

Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)

OCA
Retrieved from "https://proteopedia.openfox.io/wiki/index.php?title=1w0c&oldid=3982935"