View source for 6d23


==GLUCOSE-6-P DEHYDROGENASE (APO FORM) FROM TRYPANOSOMA CRUZI==
<StructureSection load='6d23' size='340' side='right'caption='[[6d23]], [[Resolution|resolution]] 2.85&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6d23]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Trypanosoma_cruzi Trypanosoma cruzi]. This structure supersedes the now removed PDB entry [http://oca.weizmann.ac.il/oca-bin/send-pdb?obs=1&id=4e9i 4e9i]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6D23 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6D23 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]] 2.85&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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=6d23 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6d23 OCA], [https://pdbe.org/6d23 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6d23 RCSB], [https://www.ebi.ac.uk/pdbsum/6d23 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6d23 ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/Q1WBU6_TRYCR Q1WBU6_TRYCR] 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Glucose-6-phosphate dehydrogenase (G6PDH) is the key enzyme supplying reducing power (NADPH) to the cells, by oxidation of glucose-6-phosphate (G6P), and in the process providing a precursor of ribose-5-phosphate. G6PDH is also a virulence factor of pathogenic trypanosomatid parasites. To uncover the biochemical and structural features that distinguish TcG6PDH from its human homolog, we have now solved the crystal structures of the G6PDH from Trypanosoma cruzi (TcG6PDH), alone and in complex with G6P. TcG6PDH crystallized as a tetramer, and enzymatic assays further indicated that the tetramer is the active form in the parasite, in contrast to human G6PDH, which displays higher activity as a dimer. This quaternary structure was shown to be particularly stable. The molecular reasons behind this disparity were unveiled by structural analyses: a TcG6PDH-specific residue, R323, is located at the dimer-dimer interface, critically contributing with two salt bridges per subunit that are absent in the human enzyme. This explains why TcG6PDH dimerization impaired enzyme activity. The parasite protein is also distinct in displaying a 37 amino acids extension at the N-terminus, which comprises the non-conserved C8 and C34 involved in the covalent linkage of two neighboring protomers. In addition, a cysteine triad (C53, C94 and C135) specific of Kinetoplastid G6PDHs proved critical for stabilization of TcG6PDH active site. Based on the structural and biochemical data, we posit that the N-terminal region and the catalytic site are highly dynamic. The unique structural features of TcG6PDH pave the way towards the design of efficacious and highly specific anti-trypanosomal drugs.

Glucose-6-Phosphate Dehydrogenase from the Human Pathogen Trypanosoma cruzi Evolved Unique Structural Features to Support Efficient Product Formation.,Ortiz C, Botti H, Buschiazzo A, Comini MA J Mol Biol. 2019 Mar 28. pii: S0022-2836(18)30691-0. doi:, 10.1016/j.jmb.2019.03.023. PMID:30930048<ref>PMID:30930048</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 6d23" style="background-color:#fffaf0;"></div>

==See Also==
*[[Glucose 6-phosphate dehydrogenase|Glucose 6-phosphate dehydrogenase]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Trypanosoma cruzi]]
[[Category: Botti H]]
[[Category: Buschiazzo A]]
[[Category: Comini MA]]
[[Category: Larrieux N]]
[[Category: Ortiz C]]