Please use this identifier to cite or link to this item: https://hdl.handle.net/10356/102134
Full metadata record
DC FieldValueLanguage
dc.contributor.authorRao, Srinivasa P. S.en
dc.contributor.authorBiuković, Goranen
dc.contributor.authorBasak, Sandipen
dc.contributor.authorManimekalai, Malathy Sony Subramanianen
dc.contributor.authorRishikesan, Sankaranarayananen
dc.contributor.authorRoessle, Manfreden
dc.contributor.authorDick, Thomasen
dc.contributor.authorHunke, Corneliaen
dc.contributor.authorGrüber, Gerharden
dc.date.accessioned2013-10-24T08:08:09Zen
dc.date.accessioned2019-12-06T20:50:11Z-
dc.date.available2013-10-24T08:08:09Zen
dc.date.available2019-12-06T20:50:11Z-
dc.date.copyright2013en
dc.date.issued2013en
dc.identifier.citationBiukovic, G., Basak, S., Manimekalai, M. S. S., Rishikesan, S., Roessle, M., Dick, T., et al. (2013). Variations of subunit ε of the mycobacterium tuberculosis F1Fo ATP synthase and a novel model for mechanism of action of the tuberculosis drug TMC207. Antimicrobial agents and chemotherapy, 57(1), 168-176.en
dc.identifier.issn0066-4804en
dc.identifier.urihttps://hdl.handle.net/10356/102134-
dc.description.abstractThe subunit ε of bacterial F1FO ATP synthases plays an important regulatory role in coupling and catalysis via conformational transitions of its C-terminal domain. Here we present the first low-resolution solution structure of ε of Mycobacterium tuberculosis (Mtε) F1FO ATP synthase and the nuclear magnetic resonance (NMR) structure of its C-terminal segment (Mtε103–120). Mtε is significantly shorter (61.6 Å) than forms of the subunit in other bacteria, reflecting a shorter C-terminal sequence, proposed to be important in coupling processes via the catalytic β subunit. The C-terminal segment displays an α-helical structure and a highly positive surface charge due to the presence of arginine residues. Using NMR spectroscopy, fluorescence spectroscopy, and mutagenesis, we demonstrate that the new tuberculosis (TB) drug candidate TMC207, proposed to bind to the proton translocating c-ring, also binds to Mtε. A model for the interaction of TMC207 with both ε and the c-ring is presented, suggesting that TMC207 forms a wedge between the two rotating subunits by interacting with the residues W15 and F50 of ε and the c-ring, respectively. T19 and R37 of ε provide the necessary polar interactions with the drug molecule. This new model of the mechanism of TMC207 provides the basis for the design of new drugs targeting the F1FO ATP synthase in M. tuberculosis.en
dc.language.isoenen
dc.relation.ispartofseriesAntimicrobial agents and chemotherapyen
dc.rights© 2013, American Society for Microbiologyen
dc.subjectDRNTU::Science::Biological sciencesen
dc.titleVariations of subunit ε of the mycobacterium tuberculosis F1Fo ATP synthase and a novel model for mechanism of action of the tuberculosis drug TMC207en
dc.typeJournal Articleen
dc.contributor.schoolSchool of Biological Sciencesen
dc.identifier.doi10.1128/AAC.01039-12en
item.fulltextNo Fulltext-
item.grantfulltextnone-
Appears in Collections:SBS Journal Articles

Google ScholarTM

Check

Altmetric


Plumx

Items in DR-NTU are protected by copyright, with all rights reserved, unless otherwise indicated.