7txe: Difference between revisions
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==Plasmodium falciparum Cyt c2 DSD== | |||
<StructureSection load='7txe' size='340' side='right'caption='[[7txe]], [[Resolution|resolution]] 2.30Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[7txe]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Plasmodium_falciparum_3D7 Plasmodium falciparum 3D7]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7TXE OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7TXE 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]] 2.3Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=HEC:HEME+C'>HEC</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=7txe FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7txe OCA], [https://pdbe.org/7txe PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7txe RCSB], [https://www.ebi.ac.uk/pdbsum/7txe PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7txe ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/Q8I6T6_PLAF7 Q8I6T6_PLAF7] | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
The mitochondrial electron transport chain (ETC) of Plasmodium malaria parasites is a major antimalarial drug target, but critical cytochrome (cyt) functions remain unstudied and enigmatic. Parasites express two distinct cyt c homologs (c and c-2) with unusually sparse sequence identity and uncertain fitness contributions. P. falciparum cyt c-2 is the most divergent eukaryotic cyt c homolog currently known and has sequence features predicted to be incompatible with canonical ETC function. We tagged both cyt c homologs and the related cyt c(1) for inducible knockdown. Translational repression of cyt c and cyt c(1) was lethal to parasites, which died from ETC dysfunction and impaired ubiquinone recycling. In contrast, cyt c-2 knockdown or knockout had little impact on blood-stage growth, indicating that parasites rely fully on the more conserved cyt c for ETC function. Biochemical and structural studies revealed that both cyt c and c-2 are hemylated by holocytochrome c synthase, but UV-vis absorbance and EPR spectra strongly suggest that cyt c-2 has an unusually open active site in which heme is stably coordinated by only a single axial amino acid ligand and can bind exogenous small molecules. These studies provide a direct dissection of cytochrome functions in the ETC of malaria parasites and identify a highly divergent Plasmodium cytochrome c with molecular adaptations that defy a conserved role in eukaryotic evolution. | |||
Direct tests of cytochrome c and c(1) functions in the electron transport chain of malaria parasites.,Espino-Sanchez TJ, Wienkers H, Marvin RG, Nalder SA, Garcia-Guerrero AE, VanNatta PE, Jami-Alahmadi Y, Mixon Blackwell A, Whitby FG, Wohlschlegel JA, Kieber-Emmons MT, Hill CP, Sigala PA Proc Natl Acad Sci U S A. 2023 May 9;120(19):e2301047120. doi: , 10.1073/pnas.2301047120. Epub 2023 May 1. PMID:37126705<ref>PMID:37126705</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
<div class="pdbe-citations 7txe" style="background-color:#fffaf0;"></div> | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Large Structures]] | |||
[[Category: Plasmodium falciparum 3D7]] | |||
[[Category: Hill CP]] | |||
[[Category: Whitby FG]] | |||
[[Category: Wienkers HJ]] | |||
Latest revision as of 12:48, 25 October 2023
Plasmodium falciparum Cyt c2 DSDPlasmodium falciparum Cyt c2 DSD
Structural highlights
FunctionPublication Abstract from PubMedThe mitochondrial electron transport chain (ETC) of Plasmodium malaria parasites is a major antimalarial drug target, but critical cytochrome (cyt) functions remain unstudied and enigmatic. Parasites express two distinct cyt c homologs (c and c-2) with unusually sparse sequence identity and uncertain fitness contributions. P. falciparum cyt c-2 is the most divergent eukaryotic cyt c homolog currently known and has sequence features predicted to be incompatible with canonical ETC function. We tagged both cyt c homologs and the related cyt c(1) for inducible knockdown. Translational repression of cyt c and cyt c(1) was lethal to parasites, which died from ETC dysfunction and impaired ubiquinone recycling. In contrast, cyt c-2 knockdown or knockout had little impact on blood-stage growth, indicating that parasites rely fully on the more conserved cyt c for ETC function. Biochemical and structural studies revealed that both cyt c and c-2 are hemylated by holocytochrome c synthase, but UV-vis absorbance and EPR spectra strongly suggest that cyt c-2 has an unusually open active site in which heme is stably coordinated by only a single axial amino acid ligand and can bind exogenous small molecules. These studies provide a direct dissection of cytochrome functions in the ETC of malaria parasites and identify a highly divergent Plasmodium cytochrome c with molecular adaptations that defy a conserved role in eukaryotic evolution. Direct tests of cytochrome c and c(1) functions in the electron transport chain of malaria parasites.,Espino-Sanchez TJ, Wienkers H, Marvin RG, Nalder SA, Garcia-Guerrero AE, VanNatta PE, Jami-Alahmadi Y, Mixon Blackwell A, Whitby FG, Wohlschlegel JA, Kieber-Emmons MT, Hill CP, Sigala PA Proc Natl Acad Sci U S A. 2023 May 9;120(19):e2301047120. doi: , 10.1073/pnas.2301047120. Epub 2023 May 1. PMID:37126705[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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