View source for 2tpr


==X-RAY STRUCTURE OF TRYPANOTHIONE REDUCTASE FROM CRITHIDIA FASCICULATA AT 2.4 ANGSTROMS RESOLUTION==
<StructureSection load='2tpr' size='340' side='right'caption='[[2tpr]], [[Resolution|resolution]] 2.40&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[2tpr]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Crithidia_fasciculata Crithidia fasciculata]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2TPR OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2TPR FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.4&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=FAD:FLAVIN-ADENINE+DINUCLEOTIDE'>FAD</scene></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=2tpr FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2tpr OCA], [https://pdbe.org/2tpr PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2tpr RCSB], [https://www.ebi.ac.uk/pdbsum/2tpr PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2tpr ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/TYTR_CRIFA TYTR_CRIFA] Trypanothione is the parasite analog of glutathione; this enzyme is the equivalent of glutathione reductase.
== 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/tp/2tpr_consurf.spt"</scriptWhenChecked>
    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.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=2tpr ConSurf].
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== Publication Abstract from PubMed ==
Trypanosomes and related protozoan parasites lack glutathione reductase and possess instead a closely related enzyme that serves as the reductant of a bis(glutathione)-spermidine conjugate, trypanothione. The human and parasite enzymes have mutually exclusive substrate specificities, providing a route for the design of therapeutic agents by specific inhibition of the parasite enzyme. We report here the three-dimensional structure of trypanothione reductase from Crithidia fasciculata and show that it closely resembles the structure of human glutathione reductase. In particular, the core structure surrounding the catalytic machinery is almost identical in the two enzymes. However, significant differences are found at the substrate binding sites. A cluster of basic residues in glutathione reductase is replaced by neutral, hydrophobic, or acidic residues in trypanothione reductase, consistent with the nature of the spermidine linkage and the change in overall charge of the substrate from -2 to +1, respectively. The binding site is more open in trypanothione reductase due to rotations of about 4 degrees in the domains that form the site, with relative shifts of as much as 2-3 A in residue positions. These results provide a detailed view of the residues that can interact with potential inhibitors and complement previous modeling and mutagenesis studies on the two enzymes.

X-ray structure of trypanothione reductase from Crithidia fasciculata at 2.4-A resolution.,Kuriyan J, Kong XP, Krishna TS, Sweet RM, Murgolo NJ, Field H, Cerami A, Henderson GB Proc Natl Acad Sci U S A. 1991 Oct 1;88(19):8764-8. PMID:1924336<ref>PMID:1924336</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 2tpr" style="background-color:#fffaf0;"></div>

==See Also==
*[[Trypanothione reductase|Trypanothione reductase]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Crithidia fasciculata]]
[[Category: Large Structures]]
[[Category: Kong X-P]]
[[Category: Krishna TSR]]
[[Category: Kuriyan J]]