View source for 4ytp


==CRYSTAL STRUCTURE OF PORCINE HEART MITOCHONDRIAL COMPLEX II BOUND WITH N-[(4-tert-butylphenyl)methyl]-2-(trifluoromethyl)benzamide==
<StructureSection load='4ytp' size='340' side='right'caption='[[4ytp]], [[Resolution|resolution]] 3.10&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[4ytp]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Sus_scrofa Sus scrofa]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4YTP OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4YTP 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]] 3.1&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=E23:N-(4-TERT-BUTYLBENZYL)-2-(TRIFLUOROMETHYL)BENZAMIDE'>E23</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></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=4ytp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ytp OCA], [https://pdbe.org/4ytp PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4ytp RCSB], [https://www.ebi.ac.uk/pdbsum/4ytp PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4ytp ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/SDHA_PIG SDHA_PIG] Flavoprotein (FP) subunit of succinate dehydrogenase (SDH) that is involved in complex II of the mitochondrial electron transport chain and is responsible for transferring electrons from succinate to ubiquinone (coenzyme Q). Can act as a tumor suppressor (By similarity).
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== 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>
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<div class="pdbe-citations 4ytp" style="background-color:#fffaf0;"></div>

==See Also==
*[[Succinate dehydrogenase 3D structures|Succinate dehydrogenase 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Sus scrofa]]
[[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]]