5gn7: Difference between revisions

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-'''Unreleased structure'''
-The entry 5gn7 is ON HOLD  until Paper Publication
+==Crystal structure of alternative oxidase from Trypanosoma brucei brucei complexed with cumarin derivative-17==
+<StructureSection load='5gn7' size='340' side='right'caption='[[5gn7]], [[Resolution|resolution]] 3.20&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[5gn7]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Trypanosoma_brucei_brucei Trypanosoma brucei brucei]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5GN7 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5GN7 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]] 3.2&#8491;</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=6XZ:4-[[4-(4-methoxyphenyl)piperazin-1-yl]methyl]-7,8-bis(oxidanyl)chromen-2-one'>6XZ</scene>, <scene name='pdbligand=FE:FE+(III)+ION'>FE</scene>, <scene name='pdbligand=OH:HYDROXIDE+ION'>OH</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=5gn7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5gn7 OCA], [https://pdbe.org/5gn7 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5gn7 RCSB], [https://www.ebi.ac.uk/pdbsum/5gn7 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5gn7 ProSAT]</span></td></tr>
+</table>
+== Function ==
+[https://www.uniprot.org/uniprot/AOX_TRYBB AOX_TRYBB] Catalyzes cyanide-resistant oxygen consumption. May increase respiration when the cytochrome respiratory pathway is restricted, or in response to low temperatures.
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+African trypanosomiasis, sleeping sickness in humans or nagana in animals, is a potentially fatal neglected tropical disease and a threat to 65 million human lives and 100 million small and large livestock animals in sub-Saharan Africa. Available treatments for this devastating disease are few and have limited efficacy, prompting the search for new drug candidates. Simultaneous inhibition of the trypanosomal glycerol kinase (TGK) and trypanosomal alternative oxidase (TAO) is considered a validated strategy toward the development of new drugs. Our goal is to develop a TGK-specific inhibitor for coadministration with ascofuranone (AF), the most potent TAO inhibitor. Here, we report on the identification of novel compounds with inhibitory potency against TGK. Importantly, one of these compounds (compound 17) and its derivatives (17a and 17b) killed trypanosomes even in the absence of AF. Inhibition kinetics revealed that derivative 17b is a mixed-type and competitive inhibitor for TGK and TAO, respectively. Structural data revealed the molecular basis of this dual inhibitory action, which, in our opinion, will aid in the successful development of a promising drug to treat trypanosomiasis. Although the EC50 of compound 17b against trypanosome cells was 1.77 microM, it had no effect on cultured human cells, even at 50 microM.-Balogun, E. O., Inaoka, D. K., Shiba, T., Tsuge, C., May, B., Sato, T., Kido, Y., Nara, T., Aoki, T., Honma, T., Tanaka, A., Inoue, M., Matsuoka, S., Michels, P. A. M., Watanabe, Y.-I., Moore, A. L., Harada, S., Kita, K. Discovery of trypanocidal coumarins with dual inhibition of both the glycerol kinase and alternative oxidase of Trypanosoma brucei brucei.
-Authors: Balogun, E.O., Inaoka, D.K., Shiba, T., Tsuge, T., May, B., Sato, T., Kido, Y., Takeshi, N., Aoki, T., Honma, T., Tanaka, A., Inoue, M., Matsuoka, S., Michels, P.A.M., Watanabe, Y., Moore, A.L., Harada, S., Kita, K.
+Discovery of trypanocidal coumarins with dual inhibition of both the glycerol kinase and alternative oxidase of Trypanosoma brucei brucei.,Balogun EO, Inaoka DK, Shiba T, Tsuge C, May B, Sato T, Kido Y, Nara T, Aoki T, Honma T, Tanaka A, Inoue M, Matsuoka S, Michels PAM, Watanabe YI, Moore AL, Harada S, Kita K FASEB J. 2019 Nov;33(11):13002-13013. doi: 10.1096/fj.201901342R. Epub 2019 Sep, 16. PMID:31525300<ref>PMID:31525300</ref>
-Description: Crystal structure of alternative oxidase from Trypanosoma brucei brucei complexed with cumarin derivative-17
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-[[Category: Unreleased Structures]]
+</div>
-[[Category: Honma, T]]
+<div class="pdbe-citations 5gn7" style="background-color:#fffaf0;"></div>
-[[Category: Tsuge, T]]
+== References ==
-[[Category: Matsuoka, S]]
+<references/>
-[[Category: Sato, T]]
+__TOC__
-[[Category: Shiba, T]]
+</StructureSection>
-[[Category: Inaoka, D.K]]
+[[Category: Large Structures]]
-[[Category: Kita, K]]
+[[Category: Trypanosoma brucei brucei]]
-[[Category: Moore, A.L]]
+[[Category: Aoki T]]
-[[Category: Michels, P.A.M]]
+[[Category: Balogun EO]]
-[[Category: Watanabe, Y]]
+[[Category: Harada S]]
-[[Category: Balogun, E.O]]
+[[Category: Honma T]]
-[[Category: Tanaka, A]]
+[[Category: Inaoka DK]]
-[[Category: Harada, S]]
+[[Category: Inoue M]]
-[[Category: Takeshi, N]]
+[[Category: Kido Y]]
-[[Category: Inoue, M]]
+[[Category: Kita K]]
-[[Category: May, B]]
+[[Category: Matsuoka S]]
-[[Category: Aoki, T]]
+[[Category: May B]]
-[[Category: Kido, Y]]
+[[Category: Michels PAM]]
+[[Category: Moore AL]]
+[[Category: Sato T]]
+[[Category: Shiba T]]
+[[Category: Takeshi N]]
+[[Category: Tanaka A]]
+[[Category: Tsuge T]]
+[[Category: Watanabe Y]]