TY  - JOUR
AU  - Priya, R.
AU  - Biukovic, G.
AU  - Manimekalai, M.
AU  - Lim, J.
AU  - Rao, S. S.
AU  - Grueber, G.
AU  - DESY
TI  - Solution structure of subunit (γ (γ1-204)) of the Mycobacterium tuberculosis F-ATP synthase and the unique loop of (γ165-178), representing a novel TB drug target
JO  - Journal of bioenergetics and biomembranes
VL  - 45
SN  - 0145-479X
CY  - Dordrecht [u.a.]
PB  - Springer Science + Business Media B.V
M1  - PHPPUBDB-25512
SP  - 1-9
PY  - 2013
N1  - © Springer Science+Business Media New York; Post referee fulltext in progress; Embargo 12 months from publication 
AB  - Tuberculosis, caused by the strain Mycobacterium tuberculosis, is in focus of interest due to the emergence of multi- and extensive drug-resistant TB strains. The F(1)F(O) ATP synthase is one of the essential enzymes in energy requirement of both proliferating aerobic and hypoxic dormant stage of mycobacterium life cycle, and therefore a potential TB drug target. Subunit γ of F-ATP synthases plays an important role in coupling and catalysis via conformational transitions of its N- and C-termini as well as the bottom segment of the globular domain of γ, which is in close proximity to the rotating and ion-pumping c-ring. Here we describe the first production, purification and low resolution solution structure of subunit γ (γ(1-204), Mtγ(1-204)) of the M. tuberculosis F-ATP synthase. Mtγ(1-204) is a pear-like shaped protein with a molecular weight of 23 ± 2 kDa. Protein sequence analysis of Mtγ revealed differences in the amino acid composition to γ subunits from other sources, in particular the presence of a unique stretch of 13 amino acid residues (Mtγ(165-178)). NMR studies showed that Mtγ(165-178) forms a loop of polar residues. Mtγ(165-178) has been aligned at the bottom of the globular domain of the Escherichia coli subunit γ, being in close vicinity to the polar residues R41, Q42, E44 and Q46 (M. tuberculosis nomenclature) of the c-ring. The putative role(s) of Mtγ(165-178) in coupling and as a potential drug target are discussed.
KW  - Antitubercular Agents: chemistry
KW  - Antitubercular Agents: therapeutic use
KW  - Bacterial Proteins: antagonists & inhibitors
KW  - Bacterial Proteins: chemistry
KW  - Bacterial Proteins: genetics
KW  - Bacterial Proteins: metabolism
KW  - Catalysis
KW  - Drug Delivery Systems
KW  - Enzyme Inhibitors: chemistry
KW  - Enzyme Inhibitors: therapeutic use
KW  - Mycobacterium tuberculosis: enzymology
KW  - Mycobacterium tuberculosis: genetics
KW  - Nuclear Magnetic Resonance, Biomolecular
KW  - Protein Structure, Secondary
KW  - Protein Subunits: antagonists & inhibitors
KW  - Protein Subunits: chemistry
KW  - Protein Subunits: diagnostic use
KW  - Protein Subunits: metabolism
KW  - Proton-Translocating ATPases: antagonists & inhibitors
KW  - Proton-Translocating ATPases: chemistry
KW  - Proton-Translocating ATPases: genetics
KW  - Proton-Translocating ATPases: metabolism
KW  - Recombinant Proteins: antagonists & inhibitors
KW  - Recombinant Proteins: chemistry
KW  - Recombinant Proteins: genetics
KW  - Recombinant Proteins: metabolism
KW  - Tuberculosis: drug therapy
KW  - Tuberculosis: enzymology
KW  - Antitubercular Agents (NLM Chemicals)
KW  - Bacterial Proteins (NLM Chemicals)
KW  - Enzyme Inhibitors (NLM Chemicals)
KW  - Protein Subunits (NLM Chemicals)
KW  - Recombinant Proteins (NLM Chemicals)
KW  - Proton-Translocating ATPases (NLM Chemicals)
LB  - PUB:(DE-HGF)16
C6  - pmid:23104121
UR  - <Go to ISI:>//WOS:000314899500011
DO  - DOI:10.1007/s10863-012-9486-4
UR  - https://bib-pubdb1.desy.de/record/142572
ER  -