Gerhard Gruber


Affiliation: Nanyang Technological University
Country: Singapore


  1. Bogdanović N, Sundararaman L, Kamariah N, Tyagi A, Bhushan S, Ragunathan P, et al. Structure and function of Mycobacterium-specific components of F-ATP synthase subunits α and ε. J Struct Biol. 2018;: pubmed publisher
    ..These data are discussed in context of a crosstalk between the very N-terminal amino acids of Mtε and the loop region of one c subunit of the c-ring turbine for coupling of proton-translocation and ATP synthesis activity. ..
  2. Kamariah N, Eisenhaber B, Eisenhaber F, Gruber G. Molecular mechanism of the Escherichia coli AhpC in the function of a chaperone under heat-shock conditions. Sci Rep. 2018;8:14151 pubmed publisher
    ..Our findings suggest a novel molecular mechanism for bacterial Prxs to function as chaperone at heat-shock conditions. ..
  3. Saw W, Pan A, Subramanian Manimekalai M, Grüber A, Gruber G. Structure and flexibility of non-structural proteins 3 and -5 of Dengue- and Zika viruses in solution. Prog Biophys Mol Biol. 2018;: pubmed publisher
    ..Novel mutants of the French Polynesia ZIKV NS3 linker presented, identify critical residues in protein stability and enzymatic activity. ..
  4. Balakrishna A, Manimekalai M, Grüber G. Protein-protein interactions within the ensemble, eukaryotic V-ATPase, and its concerted interactions with cellular machineries. Prog Biophys Mol Biol. 2015;119:84-93 pubmed publisher
    ..Here we describe a variety of subunit-subunit interactions within the V-ATPase enzyme during catalysis and its protein-protein assembling with key cellular machineries, essential for cellular function. ..
  5. Kamariah N, Nartey W, Eisenhaber B, Eisenhaber F, Grüber G. Low resolution solution structure of an enzymatic active AhpC10:AhpF2 ensemble of the Escherichia coli Alkyl hydroperoxide Reductase. J Struct Biol. 2016;193:13-22 pubmed publisher
    ..SAXS data-based modeling revealed the flexible C-terminal tail of EcAhpC in solution, and its exposed nature, making it possible to contact the NTD of EcAhpF for stable complex formation. ..
  6. Ho J, Sielaff H, Nadeem A, Svanborg C, Grüber G. The molecular motor F-ATP synthase is targeted by the tumoricidal protein HAMLET. J Mol Biol. 2015;427:1866-74 pubmed publisher
    ..8±0.7s(-1), no rotation could be observed in the presence of bound HAMLET. Our findings suggest that direct effects of HAMLET on the F-ATP synthase may inhibit ATP-dependent cellular processes. ..
  7. Kamariah N, Manimekalai M, Nartey W, Eisenhaber F, Eisenhaber B, Gruber G. Crystallographic and solution studies of NAD(+)- and NADH-bound alkylhydroperoxide reductase subunit F (AhpF) from Escherichia coli provide insight into sequential enzymatic steps. Biochim Biophys Acta. 2015;1847:1139-52 pubmed publisher
  8. Kamariah N, Eisenhaber B, Eisenhaber F, Grüber G. Active site CP-loop dynamics modulate substrate binding, catalysis, oligomerization, stability, over-oxidation and recycling of 2-Cys Peroxiredoxins. Free Radic Biol Med. 2018;118:59-70 pubmed publisher
    ..Based on these studies, we propose an evolution of the CP-loop with confined sequence conservation within Prxs subfamilies that might optimize the functional adaptation of Prxs into various physiological roles. ..
  9. Saw W, Pan A, Subramanian Manimekalai M, Grüber G. Structural features of Zika virus non-structural proteins 3 and -5 and its individual domains in solution as well as insights into NS3 inhibition. Antiviral Res. 2017;141:73-90 pubmed publisher
    ..Finally, the effect of ATPase inhibitors to the enzymatic active ZIKV NS3 and the individual helicase are provided. ..

More Information


  1. request reprint
    Balakrishna A, Seelert H, Marx S, Dencher N, Grüber G. Crystallographic structure of the turbine C-ring from spinach chloroplast F-ATP synthase. Biosci Rep. 2014;34: pubmed
    ..34° and diffracted to 4.5 Å resolution. Each c-ring contains 14 monomers in the asymmetric unit. The length of the c-ring is 60.32 Å, with an outer ring diameter 52.30 Å and an inner ring width of 40 Å. ..
  2. Gruber G, Marshansky V. New insights into structure-function relationships between archeal ATP synthase (A1A0) and vacuolar type ATPase (V1V0). Bioessays. 2008;30:1096-109 pubmed publisher
    ..This review will summarize the current knowledge on the structure, mechanism and regulation of A-ATP synthases and V-ATPases. The importance of V-ATPase in pathophysiology of diseases will be discussed. ..
  3. Kumar A, Balakrishna A, Nartey W, Manimekalai M, Gruber G. Redox chemistry of Mycobacterium tuberculosis alkylhydroperoxide reductase E (AhpE): Structural and mechanistic insight into a mycoredoxin-1 independent reductive pathway of AhpE via mycothiol. Free Radic Biol Med. 2016;97:588-601 pubmed publisher
  4. Sielaff H, Martin J, SINGH D, Biukovic G, Gruber G, Frasch W. Power Stroke Angular Velocity Profiles of Archaeal A-ATP Synthase Versus Thermophilic and Mesophilic F-ATP Synthase Molecular Motors. J Biol Chem. 2016;291:25351-25363 pubmed
  5. request reprint
    Gruber G. Structural features and nucleotide-binding capability of the C subunit are integral to the regulation of the eukaryotic V1Vo ATPases. Biochem Soc Trans. 2005;33:883-5 pubmed
    ..Nucleotide occupancy by subunit C, followed by conformational changes of this subunit has shed light on the mechanism of V-ATPase regulation. ..
  6. Kamariah N, Eisenhaber B, Eisenhaber F, Grüber G. Essential role of the flexible linker on the conformational equilibrium of bacterial peroxiredoxin reductase for effective regeneration of peroxiredoxin. J Biol Chem. 2017;292:6667-6679 pubmed publisher
  7. Ragunathan P, Sielaff H, Sundararaman L, Biukovic G, Subramanian Manimekalai M, SINGH D, et al. The uniqueness of subunit ? of mycobacterial F-ATP synthases: An evolutionary variant for niche adaptation. J Biol Chem. 2017;292:11262-11279 pubmed publisher
    ..Finally, we propose that the unique segment Mt?(514-549), which is accessible at the C terminus of mycobacterial subunit ?, is a promising drug epitope. ..
  8. Kumar A, Nartey W, Shin J, Manimekalai M, Gruber G. Structural and mechanistic insights into Mycothiol Disulphide Reductase and the Mycoredoxin-1-alkylhydroperoxide reductase E assembly of Mycobacterium tuberculosis. Biochim Biophys Acta Gen Subj. 2017;1861:2354-2366 pubmed publisher
    ..tuberculosis. ..
  9. Toh Y, Balakrishna A, Manimekalai M, Chionh B, Seetharaman R, Eisenhaber F, et al. Novel insights into the vancomycin-resistant Enterococcus faecalis (V583) alkylhydroperoxide reductase subunit F. Biochim Biophys Acta Gen Subj. 2017;1861:3201-3214 pubmed publisher
    ..Furthermore, mutation of Y421 is described to be essential for E. faecalis AhpF's optimal NADH-oxidative activity. ..
  10. SINGH D, Gruber G. Crystallographic and enzymatic insights into the mechanisms of Mg-ADP inhibition in the A1 complex of the A1AO ATP synthase. J Struct Biol. 2018;201:26-35 pubmed publisher
    ..The qualitative data are confirmed by quantitative results derived from fluorescence correlation spectroscopy experiments. ..
  11. Pan A, Balakrishna A, Nartey W, Kohlmeier A, Dip P, Bhushan S, et al. Atomic structure and enzymatic insights into the vancomycin-resistant Enterococcus faecalis (V583) alkylhydroperoxide reductase subunit C. Free Radic Biol Med. 2018;115:252-265 pubmed publisher
    ..Mutagenesis, enzymatic and biophysical studies reveal the effect of the unusual existence of four cysteines in EfAhpC, which might optimize the functional adaptation of the E. faecalis enzyme under various physiological conditions. ..
  12. request reprint
    Dip P, Kamariah N, Nartey W, Beushausen C, Kostyuchenko V, Ng T, et al. Key roles of the Escherichia coli AhpC C-terminus in assembly and catalysis of alkylhydroperoxide reductase, an enzyme essential for the alleviation of oxidative stress. Biochim Biophys Acta. 2014;1837:1932-43 pubmed
    ..Furthermore, using an ensemble of different truncated and mutated EcAhpC protein constructs the importance of the very C-terminus in AhpC activity and in AhpC-AhpF assembly has been demonstrated. ..
  13. Kamariah N, Eisenhaber F, Adhikari S, Eisenhaber B, Gruber G. Purification and crystallization of yeast glycosylphosphatidylinositol transamidase subunit PIG-S (PIG-S(71-467)). Acta Crystallogr Sect F Struct Biol Cryst Commun. 2011;67:896-9 pubmed publisher
    ..2?Å resolution with 91.6% completeness. The crystals belonged to space group C2, with unit-cell parameters a = 106.72, b = 59.33, c = 124.3?Å, ? = 114.19°, and contained two molecules in the asymmetric unit. ..
  14. SINGH D, Sielaff H, Sundararaman L, Bhushan S, Grüber G. The stimulating role of subunit F in ATPase activity inside the A1-complex of the Methanosarcina mazei Gö1 A1AO ATP synthase. Biochim Biophys Acta. 2016;1857:177-187 pubmed publisher
  15. Balakrishna A, Basak S, Manimekalai M, Grüber G. Crystal structure of subunits D and F in complex gives insight into energy transmission of the eukaryotic V-ATPase from Saccharomyces cerevisiae. J Biol Chem. 2015;290:3183-96 pubmed publisher
    ..Furthermore, the flexibility of the terminal helices of both subunits as well as the loop (26)GQITPETQEK(35) provides information about the regulatory step of reversible V1VO disassembly. ..
  16. Wong C, Shin J, Subramanian Manimekalai M, Saw W, Yin Z, Bhushan S, et al. AhpC of the mycobacterial antioxidant defense system and its interaction with its reducing partner Thioredoxin-C. Sci Rep. 2017;7:5159 pubmed publisher
    ..Since human cells lack AhpC, the unique N-terminal epitope of mycobacterial AhpC as well as the MbAhpC-TrxC interface represent an ideal drug target. ..
  17. Grüber A, Manimekalai M, Balakrishna A, Hunke C, Jeyakanthan J, Preiser P, et al. Structural determination of functional units of the nucleotide binding domain (NBD94) of the reticulocyte binding protein Py235 of Plasmodium yoelii. PLoS ONE. 2010;5:e9146 pubmed publisher
    ..These structures give the first insight into how nucleotide binding impacts on the overall structure of RH and demonstrates the potential use of this region as a novel drug target. ..