View source for 4ysz


==Crystal structure of Mitochondrial rhodoquinol-fumarate reductase from Ascaris suum with 2-iodo-N-[3-(1-methylethoxy)phenyl]benzamide==
<StructureSection load='4ysz' size='340' side='right'caption='[[4ysz]], [[Resolution|resolution]] 3.30&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[4ysz]] is a 8 chain structure with sequence from [https://en.wikipedia.org/wiki/Ascaris_suum Ascaris suum]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4YSZ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4YSZ 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]] 3.3&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=12J:2-IODO-N-[3-(1-METHYLETHOXY)PHENYL]BENZAMIDE'>12J</scene>, <scene name='pdbligand=EPH:L-ALPHA-PHOSPHATIDYL-BETA-OLEOYL-GAMMA-PALMITOYL-PHOSPHATIDYLETHANOLAMINE'>EPH</scene>, <scene name='pdbligand=FAD:FLAVIN-ADENINE+DINUCLEOTIDE'>FAD</scene>, <scene name='pdbligand=FES:FE2/S2+(INORGANIC)+CLUSTER'>FES</scene>, <scene name='pdbligand=HEM:PROTOPORPHYRIN+IX+CONTAINING+FE'>HEM</scene>, <scene name='pdbligand=MLI:MALONATE+ION'>MLI</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=4ysz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ysz OCA], [https://pdbe.org/4ysz PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4ysz RCSB], [https://www.ebi.ac.uk/pdbsum/4ysz PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4ysz ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/SDHB_ASCSU SDHB_ASCSU] Iron-sulfur protein (Ip) subunit of the mitochondrial electron transport chain complex II which, together with the flavoprotein (Fp) subunit forms the catalytic core of the complex (PubMed:10743611, PubMed:12742584, PubMed:17933581, PubMed:2843227, PubMed:7822332, PubMed:8435436). During the free-living egg-larvae stages, which occur in an aerobic environment, complex II acts as a succinate dehydrogenase by transferring electrons from succinate to ubiquinone (PubMed:10743611, PubMed:12742584, PubMed:17933581, PubMed:2843227, PubMed:7822332, PubMed:8435436). During the parasitic larvae and adult stages, which occur in an anaerobic environment, complex II acts as a fumarate reductase by transferring electrons from rhodoquinol to fumarate (PubMed:10743611, PubMed:12742584, PubMed:17933581, PubMed:2843227, PubMed:7822332, PubMed:8435436).<ref>PMID:10743611</ref> <ref>PMID:12742584</ref> <ref>PMID:17933581</ref> <ref>PMID:2843227</ref> <ref>PMID:7822332</ref> <ref>PMID:8435436</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Recent studies on the respiratory chain of Ascaris suum showed that the mitochondrial NADH-fumarate reductase system composed of complex I, rhodoquinone and complex II plays an important role in the anaerobic energy metabolism of adult A. suum. The system is the major pathway of energy metabolism for adaptation to a hypoxic environment not only in parasitic organisms, but also in some types of human cancer cells. Thus, enzymes of the pathway are potential targets for chemotherapy. We found that flutolanil is an excellent inhibitor for A. suum complex II (IC50 = 0.058 muM) but less effectively inhibits homologous porcine complex II (IC50 = 45.9 muM). In order to account for the specificity of flutolanil to A. suum complex II from the standpoint of structural biology, we determined the crystal structures of A. suum and porcine complex IIs binding flutolanil and its derivative compounds. The structures clearly demonstrated key interactions responsible for its high specificity to A. suum complex II and enabled us to find analogue compounds, which surpass flutolanil in both potency and specificity to A. suum complex II. Structures of complex IIs binding these compounds will be helpful to accelerate structure-based drug design targeted for complex IIs.

Structural Insights into the Molecular Design of Flutolanil Derivatives Targeted for Fumarate Respiration of Parasite Mitochondria.,Inaoka DK, Shiba T, Sato D, Balogun EO, Sasaki T, Nagahama M, Oda M, Matsuoka S, Ohmori J, Honma T, Inoue M, Kita K, Harada S Int J Mol Sci. 2015 Jul 7;16(7):15287-308. doi: 10.3390/ijms160715287. PMID:26198225<ref>PMID:26198225</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 4ysz" style="background-color:#fffaf0;"></div>

==See Also==
*[[Succinate dehydrogenase 3D structures|Succinate dehydrogenase 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Ascaris suum]]
[[Category: Large Structures]]
[[Category: Harada S]]
[[Category: Honma T]]
[[Category: Inaoka DK]]
[[Category: Inoue M]]
[[Category: Kita K]]
[[Category: Nagahama M]]
[[Category: Sakamoto K]]
[[Category: Sato D]]
[[Category: Shiba T]]
[[Category: Yamamoto A]]
[[Category: Yone A]]