4v1g: Difference between revisions
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==Crystal structure of a mycobacterial ATP synthase rotor ring== | |||
<StructureSection load='4v1g' size='340' side='right'caption='[[4v1g]], [[Resolution|resolution]] 1.55Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[4v1g]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Mycolicibacterium_phlei Mycolicibacterium phlei]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4V1G OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4V1G 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]] 1.55Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BOG:B-OCTYLGLUCOSIDE'>BOG</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=4v1g FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4v1g OCA], [https://pdbe.org/4v1g PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4v1g RCSB], [https://www.ebi.ac.uk/pdbsum/4v1g PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4v1g ProSAT]</span></td></tr> | |||
</table> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Multidrug-resistant tuberculosis (MDR-TB) is more prevalent today than at any other time in human history. Bedaquiline (BDQ), a novel Mycobacterium-specific adenosine triphosphate (ATP) synthase inhibitor, is the first drug in the last 40 years to be approved for the treatment of MDR-TB. This bactericidal compound targets the membrane-embedded rotor (c-ring) of the mycobacterial ATP synthase, a key metabolic enzyme required for ATP generation. We report the x-ray crystal structures of a mycobacterial c9 ring without and with BDQ bound at 1.55- and 1.7-A resolution, respectively. The structures and supporting functional assays reveal how BDQ specifically interacts with the rotor ring via numerous interactions and thereby completely covers the c-ring's ion-binding sites. This prevents the rotor ring from acting as an ion shuttle and stalls ATP synthase operation. The structures explain how diarylquinoline chemicals specifically inhibit the mycobacterial ATP synthase and thus enable structure-based drug design of next-generation ATP synthase inhibitors against Mycobacterium tuberculosis and other bacterial pathogens. | |||
Structure of the mycobacterial ATP synthase F rotor ring in complex with the anti-TB drug bedaquiline.,Preiss L, Langer JD, Yildiz O, Eckhardt-Strelau L, Guillemont JE, Koul A, Meier T Sci Adv. 2015 May 8;1(4):e1500106. eCollection 2015 May. PMID:26601184<ref>PMID:26601184</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
[[Category: | <div class="pdbe-citations 4v1g" style="background-color:#fffaf0;"></div> | ||
[[Category: Meier | |||
[[Category: Yildiz | ==See Also== | ||
*[[ATPase 3D structures|ATPase 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Large Structures]] | |||
[[Category: Mycolicibacterium phlei]] | |||
[[Category: Meier T]] | |||
[[Category: Preiss L]] | |||
[[Category: Yildiz O]] | |||
Latest revision as of 13:39, 10 January 2024
Crystal structure of a mycobacterial ATP synthase rotor ringCrystal structure of a mycobacterial ATP synthase rotor ring
Structural highlights
Publication Abstract from PubMedMultidrug-resistant tuberculosis (MDR-TB) is more prevalent today than at any other time in human history. Bedaquiline (BDQ), a novel Mycobacterium-specific adenosine triphosphate (ATP) synthase inhibitor, is the first drug in the last 40 years to be approved for the treatment of MDR-TB. This bactericidal compound targets the membrane-embedded rotor (c-ring) of the mycobacterial ATP synthase, a key metabolic enzyme required for ATP generation. We report the x-ray crystal structures of a mycobacterial c9 ring without and with BDQ bound at 1.55- and 1.7-A resolution, respectively. The structures and supporting functional assays reveal how BDQ specifically interacts with the rotor ring via numerous interactions and thereby completely covers the c-ring's ion-binding sites. This prevents the rotor ring from acting as an ion shuttle and stalls ATP synthase operation. The structures explain how diarylquinoline chemicals specifically inhibit the mycobacterial ATP synthase and thus enable structure-based drug design of next-generation ATP synthase inhibitors against Mycobacterium tuberculosis and other bacterial pathogens. Structure of the mycobacterial ATP synthase F rotor ring in complex with the anti-TB drug bedaquiline.,Preiss L, Langer JD, Yildiz O, Eckhardt-Strelau L, Guillemont JE, Koul A, Meier T Sci Adv. 2015 May 8;1(4):e1500106. eCollection 2015 May. PMID:26601184[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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