Department of Biology & Biochemistry
ravi_acharya

Professor of Structural Molecular Biology

4 South 0.29

Email: K.R.Acharya@bath.ac.uk

Tel: +44 (0) 1225 386238

 
 
Research group website

Structural Molecular Biology

 

Prof Ravi Acharya 

Profile

Our research is aimed at elucidating the structure-function relationship of molecules involved in normal and disease processes with a more recent focus on angiogenic molecules(angiogenin and VEGF family members) and molecules involved in inflammatory processes (toxins), functions in the vascular system such as Angiotensin-I converting enzyme (ACE) and glycosyltransferases.

We have complemented our structural studies using X-ray crystallography in understanding protein-protein/carbohydrate interactions with high-throughput compound library screening, structure based design of inhibitors, computational and biophysical techniques as well as protein engineering, enzyme kinetics, cell and developmental biology approaches.

To achieve this goal we have been ably supported by a number of very active collaborators (including clinicians and biologists) who are international experts. The long term objective of our research is directed towards the design of new pharmacological agents to treat human diseases.

  • PhD, Bangalore University, India (1982)
  • Scientist at the National Chemical Laboratory, Pune, India (1982-1983)
  • Post-doctoral Research Scientist, Laboratory of Molecular Biophysics, Oxford (1984-1990)
  • Sir E.P.Abraham Junior Research Fellow, Linacre College, Oxford University (1988-1990)
  • Lecturer (1990-1994), Reader (1994-1998), University of Bath
  • Leverhulme Trust Research Fellow, University of Bath (1993-1994)
  • Nuffield Foundation Science Research Fellow, University of Bath (1994-1995)
  • Royal Society - Leverhulme Trust Senior Research Fellow, University of Bath (2001-2002)
  • Wellcome Trust Research Leave Fellow, University of Bath (2004-2007)
  • Royal Society Industry Research Fellow, University of Bath (2007-2011)
  • Elected Fellow of Society of Biology (2011)
  • Excellence in Doctoral Supervision Award - University of Bath (2012)
  • Syntaxin Ltd (UK) Research Fellow (since October 2011)
  • Professor of Structural Biology, University of Bath (since May 1998)

Publications

Bradshaw, W.J., Kirby, J.M., Thiyagarajan, N., Chambers, C.J., Davies, A.H., Roberts, A.K., Shone, C.C. and Acharya, K.R., 2014. The structure of the cysteine protease and lectin-like domains of Cwp84, a surface layer-associated protein from Clostridium difficile. Acta Crystallographica Section D-Biological Crystallography, 70 (7), pp. 1983-1993.

Acharya, K.R. and Ackerman, S.J., 2014. Eosinophil granule proteins : Form and function. Journal of Biological Chemistry, 289 (25), pp. 17406-17415.

Michaud, A., Acharya, K., Masuyer, G., Quenech'du, N., Gribouval, O., Morinière, V., Gubler, M.-C. and Corvol, P., 2014. Absence of cell surface expression of human ACE leads to perinatal death. Human Molecular Genetics, 23 (6), pp. 1479-1491.

Masuyer, G., Mohd, A., Czarny, B., Beau, F., Schwager, S. L. U., Sturrock, E. D., Isaac, R. E., Dive, V. and Acharya, K. R., 2014. Crystal structures of highly specific phosphinic tripeptide enantiomers in complex with the angiotensin-I converting enzyme. FEBS Journal, 281 (3), pp. 943-956.

Yates, C. J., Masuyer, G., Schwager, S. L. U., Mohd, A., Sturrock, E. D. and Acharya, K. R., 2014. Molecular and thermodynamic mechanisms of the chloride-dependent human angiotensin-I-converting enzyme (ACE). Journal of Biological Chemistry, 289 (3), pp. 1798-1814.

Harrison, C. and Acharya, K. R., 2014. Forthcoming. ACE for all : A molecular perspective. Journal of Cell Communication and Signaling

Douglas, R. G., Sharma, R. K., Masuyer, G., Lubbe, L., Zamora, I., Acharya, K. R., Chibale, K. and Sturrock, E. D., 2014. Fragment-based design for the development of N-domain-selective angiotensin-1-converting enzyme inhibitors. Clinical Science, 126 (4), pp. 305-313.

Iyer, S., Holloway, D. E. and Acharya, K. R., 2013. Crystal structures of murine angiogenin-2 and -3 - probing ‘structure - function’ relationships amongst angiogenin homologues. FEBS Journal, 280 (1), pp. 302-318.

Thiyagarajan, N. and Acharya, K.R., 2013. Crystal structure of human angiogenin with an engineered loop exhibits conformational flexibility at the functional regions of the molecule. FEBS Open Bio, 3, pp. 65-70.

Walker, N. J., Clark, E. A., Ford, D. C., Bullifent, H. L., Mcalister, E. V., Duffield, M. L., Acharya, K. R. and Oyston, P. C. F., 2012. Structure and function of cytidine monophosphate kinase from Yersinia pseudotuberculosis, essential for virulence but not for survival. Open Biology, 2 (Dec), 120142.

Akif, M., Masuyer, G., Bingham, R. J., Sturrock, E. D., Isaac, R. E. and Acharya, K. R., 2012. Structural basis of peptide recognition by the angiotensin-1 converting enzyme homologue AnCE from Drosophila melanogaster. FEBS Journal, 279 (24), pp. 4525-4534.

Masuyer, G., Schwager, S. L. U., Sturrock, E. D., Isaac, R. E. and Acharya, K. R., 2012. Molecular recognition and regulation of human angiotensin-I converting enzyme (ACE) activity by natural inhibitory peptides. Scientific Reports, 2, 717.

Thiyagarajan, N., Ferguson, R., Subramanian, V. and Acharya, K. R., 2012. Structural and molecular insights into the mechanism of action of human angiogenin-ALS variants in neurons. Nature Communications, 3, 1121.

Sturrock, Edward D, 2012. Crystal. DK1984008 (T3), 01 October 2012.

Stancombe, P. R., Masuyer, G., Birch-Machin, I., Beard, M., Foster, K. A., Chaddock, J. A. and Acharya, K. R., 2012. Engineering botulinum neurotoxin domains for activation by toxin light chain. FEBS Journal, 279 (3), pp. 515-523.

Masuyer, G., Jabeen, T., Oberg, C. T., Leffler, H., Nilsson, U. J. and Acharya, K. R., 2012. Inhibition mechanism of human galectin-7 by a novel galactose-benzylphosphate inhibitor. FEBS Journal, 279 (2), pp. 193-202.

Anthony, C. S., Masuyer, G., Sturrock, E. D. and Acharya, K. R., 2012. Structure based drug design of angiotensin-i converting enzyme inhibitors. Current Medicinal Chemistry, 19 (6), pp. 845-855.

Thiyagarajan, N., Pham, T. T. K., Stinson, B., Sundriyal, A., Tumbale, P., Lizotte-waniewski, M., Brew, K. and Acharya, K. R., 2012. Structure of a metal-independent bacterial glycosyltransferase that catalyzes the synthesis of histo-blood group A antigen. Scientific Reports, 2, 940.

Masuyer, G., Stancombe, P., Chaddock, J. A. and Acharya, K. R., 2011. Structures of engineered Clostridium botulinum neurotoxin derivatives. Acta Crystallographica Section F-Structural Biology and Crystallization Communications, 67 (12), pp. 1466-1472.

Holloway, D. E., Singh, U. P., Shogen, K. and Acharya, K. R., 2011. Crystal structure of Onconase at 1.1 angstrom resolution - insights into substrate binding and collective motion. FEBS Journal, 278 (21), pp. 4136-4149.

Iyer, S. and Acharya, K. R., 2011. Tying the knot: The cystine signature and molecular-recognition processes of the vascular endothelial growth factor family of angiogenic cytokines. FEBS Journal, 278 (22), pp. 4304-4322.

Akif, M., Masuyer, G., Schwager, S. L. U., Bhuyan, B. J., Mugesh, G., Isaac, R. E., Sturrock, E. D. and Acharya, K. R., 2011. Structural characterization of angiotensin I-converting enzyme in complex with a selenium analogue of captopril. FEBS Journal, 278 (19), pp. 3644-3650.

Kirby, J. M., Thiyagarajan, N., Roberts, A. K., Shone, C. C. and Acharya, K. R., 2011. Expression, purification, crystallization and preliminary crystallographic analysis of a putative Clostridium difficile surface protein Cwp19. Acta Crystallographica Section F-Structural Biology and Crystallization Communications, 67 (7), pp. 762-767.

Holbourn, K. P., Malfois, M. and Acharya, K. R., 2011. First structural glimpse of CCN3 and CCN5 multifunctional signaling regulators elucidated by small angle X-ray scattering. Journal of Biological Chemistry, 286 (25), pp. 22243-22249.

Davies, A. H., Roberts, A. K., Shone, C. C. and Acharya, K. R., 2011. Super toxins from a super bug: structure and function of Clostridium difficile toxins. Biochemical Journal, 436 (3), pp. 517-526.

Akif, M., Schwager, S. L., Anthony, C. S., Czarny, B., Beau, F., Dive, V., Sturrock, E. D. and Acharya, K. R., 2011. Novel mechanism of inhibition of human angiotensin-I-converting enzyme (ACE) by a highly specific phosphinic tripeptide. Biochemical Journal, 436 (1), pp. 53-59.

Holbourn, K. P. and Acharya, K. R., 2011. Cloning, expression and purification of the CCN family of proteins in Escherichia coli. Biochemical and Biophysical Research Communications, 407 (4), pp. 837-841.

Holbourn, K. P., Lloyd, M. D., Thompson, A. S., Threadgill, M. D. and Acharya, K. R., 2011. Cloning, purification, crystallization and preliminary crystallographic analysis of the human histone deacetylase sirtuin 1. Acta Crystallographica Section F-Structural Biology and Crystallization Communications, 67 (4), pp. 461-463.

Chaddock, J. A. and Acharya, K. R., 2011. Engineering toxins for 21st century therapies. FEBS Journal, 278 (6), pp. 899-904.

Masuyer, G., Beard, M., Cadd, V. A., Chaddock, J. A. and Acharya, K. R., 2011. Structure and activity of a functional derivative of Clostridium botulinum neurotoxin B. Journal of Structural Biology, 174 (1), pp. 52-57.

Thiyagarajan, N., Smith, B. D., Raines, R. T. and Acharya, K. R., 2011. Functional and structural analyses of N-acylsulfonamide-linked dinucleoside inhibitors of RNase A. FEBS Journal, 278 (3), pp. 541-549.

Clark, E. A., Walker, N., Ford, D. C., Cooper, I. A., Oyston, P. C. F. and Acharya, K. R., 2011. Molecular Recognition of Chymotrypsin by the Serine Protease Inhibitor Ecotin from Yersinia pestis. Journal of Biological Chemistry, 286 (27), pp. 24015-24022.

Brew, K., Tumbale, P. and Acharya, K. R., 2010. Family 6 Glycosyltransferases in Vertebrates and Bacteria: Inactivation and Horizontal Gene Transfer May Enhance Mutualism between Vertebrates and Bacteria. Journal of Biological Chemistry, 285 (48), pp. 37121-37127.

Anthony, C. S., Corradi, H. R., Schwager, S. L. U., Redelinghuys, P., Georgiadis, D., Dive, V., Acharya, K. R. and Sturrock, E. D., 2010. The N domain of human angiotensin-I-converting enzyme: The role of N-glycosylation and the crystal structure in complex with an N domain-specific phosphinic inhibitor, RXP407. Journal of Biological Chemistry, 285 (46), pp. 35685-35693.

Sundriyal, A., Roberts, A. K., Ling, R., McGlashan, J., Shone, C. C. and Acharya, K. R., 2010. Expression, purification and cell cytotoxicity of actin-modifying binary toxin from Clostridium difficile. Protein Expression and Purification, 74 (1), pp. 42-48.

de Andrade, M. C. C., Affonso, R., Fernandes, F. B., Febba, A. C., da Silva, I., Stella, R. C. R., Marson, O., Jubilut, G. N., Hirata, I. Y., Carmona, A. K., Corradi, H., Acharya, K. R., Sturrock, E. D. and Casarini, D. E., 2010. Spectroscopic and structural analysis of somatic and N-domain angiotensin I-converting enzyme isoforms from mesangial cells from Wistar and spontaneously hypertensive rats. International Journal of Biological Macromolecules, 47 (2), pp. 238-243.

Akif, M., Ntai, I., Sturrock, E. D., Isaac, R. E., Bachmann, B. O. and Acharya, K. R., 2010. Crystal structure of a phosphonotripeptide K-26 in complex with angiotensin converting enzyme homologue (AnCE) from Drosophila melanogaster. Biochemical and Biophysical Research Communications, 398 (3), pp. 532-536.

Iyer, S., Darley, P. I. and Acharya, K. R., 2010. Structural insights into the binding of vascular endothelial growth factor-B by VEGFR-1(D2): recognition and specificity. Journal of Biological Chemistry, 285 (31), pp. 23779-23789.

Akif, M., Georgiadis, D., Mahajan, A., Dive, V., Sturrock, E. D., Isaac, R. E. and Acharya, K. R., 2010. High-resolution crystal structures of drosophila melanogaster angiotensin-converting enzyme in complex with novel inhibitors and antihypertensive drugs. Journal of Molecular Biology, 400 (3), pp. 502-517.

Acharya, Ravi, 2010. Crystal Structure of an Angiotensin-Converting Enzyme (ACE) and Uses Thereof. C12Q1/37-US2010160180 (A1), 24 June 2010.

Leese, M. P., Jourdan, F., Kimberley, M. R., Cozier, G. E., Thiyagarajan, N., Stengel, C., Regis-Lydi, S., Foster, P. A., Newman, S. P., Acharya, K. R., Ferrandis, E., Purohit, A., Reed, M. J. and Potter, B. V. L., 2010. Chimeric microtubule disruptors. Chemical Communications, 46 (17), pp. 2907-2909.

Cozier, G. E., Leese, M. P., Lloyd, M. D., Baker, M. D., Thiyagarajan, N., Acharya, K. R. and Potter, B. V. L., 2010. Structures of human carbonic anhydrase II/inhibitor complexes reveal a second binding site for steroidal and nonsteroidal inhibitors. Biochemistry, 49 (16), pp. 3464-3476.

Woo, L. .W. L., Jackson, T., Putey, A., Cozier, G., Leonard, P., Acharya, K. R., Chander, S. K., Purohit, A., Reed, M. J. and Potter, B. V. L., 2010. Highly potent first examples of dual aromatase-steroid sulfatase inhibitors based on a biphenyl template. Journal of Medicinal Chemistry, 53 (5), pp. 2155-2170.

Holbourn, K. P., Perbal, B. and Acharya, K. R., 2010. Asking the Right Questions: What Can the Structure of the CCN Protein Domains Tell Us? In: CCN Proteins in Health and Disease: An Overview of the Fifth International Workshop on the CCN Family of Genes. Berlin: Springer, pp. 15-40.

Acharya, Ravi, 2009. Ace N-domain crystal. A61K-ZA200806312 (A), 30 December 2009.

Kirby, J. M., Ahern, H., Roberts, A. K., Kumar, V., Freeman, Z., Acharya, K. R. and Shone, C. C., 2009. Cwp84, a surface-associated Cysteine Protease, plays a role in the maturation of the surface layer of Clostridium difficile. Journal of Biological Chemistry, 284 (50), pp. 34666-34673.

Mitsiki, E., Papageorgiou, A. C., Iyer, S., Thiyagarajan, N., Prior, S. H., Sleep, D., Finnis, C. and Acharya, K. R., 2009. Structures of native human thymidine phosphorylase and in complex with 5-iodouracil. Biochemical and Biophysical Research Communications, 386 (4), pp. 666-670.

Jamaluddin, H., Tumbale, P., Ferns, T. A., Thiyagarajan, N., Brew, K. and Acharya, K. R., 2009. Crystal structure of α-1,3-galactosyltransferase (α3GT) in a complex with p-nitrophenyl-β-galactoside (pNPβGal). Biochemical and Biophysical Research Communications, 385 (4), pp. 601-604.

Masuyer, G., Thiyagarajan, N., James, P. L., Marks, P. M. H., Chaddock, J. A. and Acharya, K. R., 2009. Crystal structure of a catalytically active, non-toxic endopeptidase derivative of Clostridium botulinum toxin A. Biochemical and Biophysical Research Communications, 381 (1), pp. 50-53.

Holbourn, K. P., Perbal, B. and Acharya, K. R., 2009. Proteins on the catwalk : modelling the structural domains of the CCN family of proteins. Journal of Cell Communication and Signaling, 3 (1), pp. 25-41.

Holloway, D. E., Chavali, G. B., Leonidas, D. D., Baker, M. D. and Acharya, K. R., 2009. Influence of Naturally-Occurring 5 '-Pyrophosphate-Linked Substituents on the Binding of Adenylic Inhibitors to Ribonuclease A: An X-Ray Crystallographic Study. Biopolymers, 91 (12), pp. 995-1008.

Sundriyal, A., Roberts, A. K., Shone, C. C. and Acharya, K. R., 2009. Structural basis for substrate recognition in the enzymatic component of ADP-ribosyltransferase toxin CDTa from clostridium difficile. Journal of Biological Chemistry, 284 (42), pp. 28713-28719.

Holbourn, K. P., Acharya, K. R. and Perbal, B., 2008. The CCN family of proteins: structure-function relationships. Trends in Biochemical Sciences, 33 (10), pp. 461-473.

Kazakou, K., Holloway, D. E., Prior, S. H., Subramanian, V. and Acharya, K. R., 2008. Ribonuclease A homologues of the zebrafish: polymorphism, crystal structures of two representatives and their evolutionary implications. Journal of Molecular Biology, 380 (1), pp. 206-222.

Subramanian, V., Crabtree, B. and Acharya, K. R., 2008. Human angiogenin is a neuroprotective factor and amyotrophic lateral sclerosis associated angiogenin variants affect neurite extension/pathfinding and survival of motor neurons. Human Molecular Genetics, 17 (1), pp. 130-149.

Leonard, P., Scotney, P. D., Jabeen, T., Iyer, S., Fabri, L. J., Nash, A. D. and Acharya, K. R., 2008. Crystal Structure of Vascular Endothelial Growth Factor-B in Complex with a Neutralising Antibody Fab Fragment. Journal of Molecular Biology, 384 (5), pp. 1203-1217.

Ulrich, M., Petre, A., Youhnovski, N., Promm, F., Schirle, M., Schumm, M., Pero, R. S., Doyle, A., Checkel, J., Kita, H., Thiyagarajan, N., Acharya, K. R., Schmid-Grendelmeier, P., Simon, H. U., Schwarz, H., Tsutsui, M., Shimokawa, H., Bellon, G., Lee, J. J., Przybylski, M. and Doring, G., 2008. Post-translational tyrosine nitration of eosinophil granule toxins mediated by eosinophil peroxidase. Journal of Biological Chemistry, 283 (42), pp. 28629-28640.

Tumbale, P., Jamaluddin, H., Thiyagarajan, N., Acharya, K. R. and Brew, K., 2008. Screening a limited structure-based library identifies UDP-GalNAc-specific mutants of α-1,3-galactosyltransferase. Glycobiology, 18 (12), pp. 1036-1043.

Tumbale, P., Jamaluddin, H., Thiyagarajan, N., Brew, K. and Acharya, K. R., 2008. Structural Basis of UDP-galactose Binding by α-1,3-Galactosyltransferase (α3GT): Role of Negative Charge on Aspartic Acid 316 in Structure and Activity. Biochemistry, 47 (33), pp. 8711-8718.

Jabeen, T., Leonard, P., Jamaluddin, H. and Acharya, K. R., 2008. Structure of mouse IP-10, a chemokine. Acta Crystallographica Section D-Biological Crystallography, 64, pp. 611-619.

This list was generated on Mon Oct 20 13:34:24 2014 IST.

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