Prof. M R N Murthy

Research Focus Key Words:

Protein structure and function; virus structure and assembly, X-ray crystallography

Background:

The structures of two plant viruses, sesbania mosaic virus and physalis mottle virus, and several virus-like particles obtained by expressing in E. coli the coat proteins of these viruses have been determined. Sesbania mosaic virus coat protein in which epitopes from other pathogenic organisms have been introduced assemble into virus like particles with novel biotechnological applications. The structure, function and reaction mechanism of several PLP-dependent enzymes including serinehydroxymethyl transferase, actetylornithine aminotransferase, D-serine deaminase, D-cysteine desulfhydrase, arginine decarboxylase, pyridoxal kinase and diaminopropionate ammonia lyase have been investigated. Functional importance of survival proteins SurE, YdaA, YnaF that are over-expressed when bacterial cells are subjected to environmental stresses have been established. X-ray crystal structures of triosephosphate isomerase, adenylosuccinate synthase and hypoxanthine guanine phosphoribosyl transferase from the malaria parasite Plasmodium falciparum have been determined. The structures of methylisocitrate lyase, methylcitrate synthase, acetate kinase, propionate kinase and threonine deaminase that are overexpressed when Salmonella typhimurium is grown on propionate as the sole source of carbon have been determined. Structure of three thiolase-like proteins from mycobacterium that could be potential drug targets have been determined. Structure of Photorhabdusluminescens oxalate decaboxylase, which is likely to be a key protein useful for the generation of insect resistant transgenic plants, has been determined. A marathon molecular replacement procedure has been developed and shown to be useful for determining several hitherto intractable crystal structures of unknown or unidentified proteins.

Education

B.Sc (Hons), Bangalore University, 1970
M.Sc. IIT, Madras, 1972
Ph.D. IISc, Bengaluru, 1977

Postdoctoral Research

Purdue University, USA 1977-1981

Professional Experience

Senior research fellow, IISc 1982-1983;
Assistant Professor, Molecular Biophysics Unit, IISc, Bengaluru, 1983-1989;
Associate Professor, IISc, 1989-1994;
Professor, 1994-2015, J.C. Bose fellow, IISc -2003-2018;
INSA senior scientist, IIsc, 2016-2019, Honorary Professor, IBAB, Bengaluru, 2018-c.

Research Interest Profile:

Protein structure and function; Molecular Evolution, virus structure and assembly, X-ray crystallography- theory and practise

Group members:

Nil

Collaborators:

Prof. H.S. Savithri, IISc, Bengaluru
Prof. P. Balaram, IISc, Bengaluru
Prof. H. Balaram, JNCSAR, Bengaluru

List of Publications and patents since 2009

1. FEBS Journal Volume 278, Issue 16, pages 2879–2891. 2011
   Current Science (2010) 98: 346-352.Structures of mannose-6-phosphate isomerase from Salmonella typhimurium bound to metal atoms and substrate: implications for catalytic mechanism.
   Sagurthi SR, Gowda G, Savithri HS, Murthy MR. Acta Crystallogr D BiolCrystallogr. 65, 724-732. 2009
2. Detection of the protein dimers, multiple monomeric states and hydrated forms of Plasmodium falciparum triosephosphate isomerase in the gas phase.
   Thakur SS, Deepalakshmi PD, Gayathri P, Banerjee M, Murthy MR, Balaram P.
   Protein Eng Des Sel., 22, 289-304. 2009
3. Structural and functional studies of Bacillus stearothermophilus serine hydroxymethyltransferase: the role of Asn(341), Tyr(60) and Phe(351) in tetrahydrofolate binding.
   Pai VR, Rajaram V, Bisht S, Bhavani BS, Rao NA, Murthy MR, Savithri HS.
   Biochem J., 418, 635-642. 2009
4. Biochemical and structural characterization of residue 96 mutants of Plasmodium falciparum triosephosphate isomerase: active-site loop conformation, hydration and identification of a dimer-interface ligand-binding site.
   Gayathri P; Banerjee Mousumi; Vijayalakshmi A; Balaram Hemalatha;  Balaram P; Murthy M R N.
   Acta crystallogrD65: 847-57. 2009.
5. A single point mutation disrupts the capsid assembly in Sesbania Mosaic Virus resulting in a stable isolated dimer.
   Pappachan Anju; ChinnathambiSubashchandrabose; Satheshkumar P S; Savithri H S; Murthy M R N
   Virology 392: 215-21, 2009.
6. Structure and assembly of Sesbania mosaic virus.
   Savithri H. S. and Murthy M.R.N.
   Current Science (2010) 98: 346-352.
7. NSs Encoded by Groundnut Bud Necrosis Virus {GBNV-To (K)} is a Bi-functional Enzyme
   Lokesh Bhushan, Rashmi Panigrahi, D. Srisathiyanarayanan, M.R.N. Murthy and H. S. Savithri
   PLoS ONE 5(3): e9757. https://doi.org/10.1371/journal.pone.0009757. 2010
8. Preliminary X-ray crystallographic analysis of 2-methylcitrate synthase from Salmonella typhimurium,
   Chittori, S., Simanshu, D.K., Savithri, H.S.  and Murthy, M.R.N.
   Acta Cryst., F66, 467-470. 2010
9. Priliminary X-ray Crystallographic studies on acetate kinase (AckA) from Salmonella typhimurium in two crystal forms
   Chittiro, S. Savithri, H.S. and Murthy, M.R.N.
   Acta Cryst Sect F 67: 2658-1661, 2011
10. Crystal structure of Salmonella typhimurium 2-methylcitrate synthase: Insights on domain movement and substrate specificity.
    Chittori S, Savithri HS, Murthy MR.
    J Struct Biol. Apr;174(1):58-68. Epub 2010 Oct 21. PubMed PMID: 20970504. 2011.
11. Revisiting the Mechanism of the Triosephosphate Isomerase Reaction: The Role of the Fully Conserved Glutamic Acid 97 Residue
    Moumita Samanta, M. R. N. Murthy, Hemalatha Balaram, and Padmanabhan Balaram
    Chem Bio Chem, 12, 1 – 12. 2011
12. Probing the role of the fully conserved Cys126 in triosephosphate isomerase by site-specific mutagenesis – distal effects on dimer stability
    Moumita Samanta, Mousumi Banerjee, Mathur R. N. Murthy, Hemalatha Balaram and Padmanabhan Balaram
    FEBS Journal 278, 1932–1943. 2011
13. Crystal structures of open and closed forms of d-serine deaminase from Salmonella typhimurium – implications on substrate specificity and catalysis
    Bharath, S.R., Bisht, S., Savithri, H.S., and Murthy, M.R.N.
    FEBS Journal Volume 278, Issue 16, pages 2879–2891. 2011
14. Revisiting the mechanism of the triosephosphate isomerase reaction: the role of the fully conserved glutamic acid 97 residue.
    Samanta M, Murthy MR, Balaram H, Balaram P.
    ChemBioChem, 12:1886-1896. 2011
15. Cloning, expression, purification and preliminary X-ray diffraction studies of a putative Mycobacterium smegmatis thiolase.
    Janardan, N,, Paul, A,, Harijan, R.K,, Wierenga, R. K and Murthy, M.R.N
    Acta Crystallogr Sect F Struct BiolCrystCommun. 67, 817-820. Epub 2011 Jun 30. 2011
16. Structural and Mutational Studies on Substrate Specificity and Catalysis of Salmonellatyphimurium D-Cysteine Desulfhydrase
    Bharath, S.R., Bisht, S, Harijan, R., Savithri, H.S. and Murthy, M. R. N.
    PLoS ONE. e36267 https://doi.org/10.1371/journal.pone.0036267. 2012.
17. Crystal Structure of Escherichia coli Diaminopropionate Ammonia-lyase Reveals Mechanism of Enzyme Activation and Catalysis
    Bisht, S., Rajaram, V., Bharath, S.R.,  Kalyani, J.N., Khan, F., Rao, A.N., Savothri, H.S. and Murthy, M.R.N. (2012)
    J Biol Chem 287, 20369-20381
18. Intrincically disordered domains ossesbania mosaic virus encoded proteins Smita Nair, Murthy,M.R.N. and Savithri, H.S.
    in “Flexible viruses”, eds V.N. Uverky and S. Longhi, John Wiley & Sons, Inc., pp 257-276 (2012)
19. Structural and mechanistic investigations on Salmonella typhimurium acetate kinase (AckA): identification of a putative ligand binding pocket at the dimeric interface.
    Chittori S, Savithri HS, Murthy MR.
    BMC Struct Biol. 2012 Oct 2;12:24. doi: 10.1186/1472-6807-12-24.
20. Crystal structure of a monomeric thiolase-like protein type 1 (TLP1) from Mycobacteriumsmegmatis.
    Janardan N, Harijan RK, Wierenga RK, Murthy MR
    PLoS  One. 2012;7(7):e41894. doi: 10.1371/journal.pone.0041894.
21. Sesbania mosaic virus peptidase
    Savithri, H.S., Murthy, M.R.N. and Govind, K (2013)
    In Handbook of proteolytic enzymes, ed. Neil D Rawlings and Guy S Silvesen. Elesevior Ltd. Acamedic press pp 3141-3148
22. Identification of key amino acid residues in the catalytic mechanism
    of diaminopropionateammonialyase from Salmonella typhimurium.
    Kalyani JN, Bisht S, Lakshmikanth M, Murthy MR, Savithri HS.
    FEBS J. 2013 Aug 8. doi: 10.1111/febs.12474. [Epub ahead of print] PubMed PMID: 23927374.
23. Crystal structures of SCP2-thiolases of Trypanosomatidae, human pathogens causing widespread tropical diseases: the importance for catalysis of the cysteine of the unique HDCF loop.
    Harijan RK, Kiema TR, Karjalainen MP, Janardan N, Murthy MR, Weiss MS, Michels PA, Wierenga RK.
    Biochem J. 2013 Aug 2. [Epub ahead of print] PubMed PMID: 23909465.
24. Mechanistic features of Salmonella typhimurium propionate kinase (TdcD): Insights from kinetic and crystallographic studies.
    Chittori S, Simanshu DK, Banerjee S, Murthy AM, Mathivanan S, Savithri HS, Murthy MR.
    BiochimBiophys Acta. 2013 Jun 5;1834(10):2036-2044. doi: 10.1016/j.bbapap.2013.05.020. [Epub ahead of print] PubMed PMID: 23747922.
25. Fold type II pyridoxal 5ʹ-phosphate dependent enzymes: structure, substrate recognition and catalysis.  (Book Chapter),
    Bisht S, Bharath SR, Savithri HS and Murthy MR.
    Biomolecular Forms and Functions: A Celebration of 50 Years of the Ramachandran Map, Ed Manju Bansal and N. Srinivasan, World Scientific Publishing Company, 2013, 398-416.
26. Successful data recovery from oscillation photographs containing strong polycrystalline diffraction rings from an unknown small-molecule contaminant: preliminary structure solution of Salmonella typhimurium pyridoxal kinase (PdxK).
    G Deka, J N Kalyani, J F Benazir, H S Savithri, M R N Murthy (2014)
    Acta crystallographica. Section F, Structural biology communications. 526-529.
27. Phylogenetic relationships and classification of thiolases and thiolase-like proteins of Mycobacterium tuberculosis and Mycobacterium smegmatis
    Padmanabhan Anbazhagan, Rajesh K. Harijan, Tiila R. Kiema, Neelanjana Janardan, M.R.N. Murthy, Paul A.M. Michels, André H. Juffer, Rik K.
    Tuberculosis (Edinb). 2014 Jul;94(4):405-12. doi: 10.1016/j.tube.2014.03.003. Epub 2014 Apr 4.
28. Crystal structures of SCP2-thiolases of Trypanosomatidae, human pathogens causing widespread tropical diseases: the importance for catalysis of the cysteine of the unique HDCF loop.
    Harijan RK, Kiema TR, Karjalainen MP, Janardan N, Murthy MR, et al
    Biochem J 455: 119-130. 2014.
29. Viruses and viral proteins
    Nuria Verdaguer, Diego Ferrero and Mathur R. N. Murthy
    IUCrJ, 1, 492-504. 2014.
30. Structural and kinetic studies on Adenylosuccinate Lyase from Mycobacterium smegmatis and Mycobacterium tuberculosis provide new insights on the catalytic residues of the enzyme.
    Banerjee, Sanchari& J Agrawal, Monika & Mishra, Dipti & Sharan, Siddharth &Balaram, Hemalatha & Savithri, Handanahal& Murthy, Mathur.
    The FEBS journal. 281. 10.1111/febs.12730. 2014.
31. Structural and functional analysis of two universal stress proteins YdaA and YnaF from Salmonella typhimurium: Possible roles in microbial stress tolerance.
    M Bangera, R Panigrahi, S R Sagurthi, H S Savithri, M R N Murthy
    J. Struct. Biol. 189, 235-241. 2015.
32. Dramatic structural changes resulting from the loss of a crucial hydrogen bond in the hinge region involved in C-terminal helix swapping in SurE: a survival protein from Salmonellatyphimurium. 
    Mathiharan YK, Pappachan A, Savithri HS, Murthy MR.
    PLoS One. 2013;8(2):e55978..
33. Structural studies on chimeric Sesbania mosaic virus coat protein: Revisiting SeMV assembly.
    Gulati A, Murthy A, Abraham A, Mohan K, Natraj U, Savithri HS, Murthy MR.
    Virology. 2016, 489: 34-43
34. Structural studies on tobacco streak virus coat protein: Insights into the pleomorphic nature of ilarviruses.
    Gulati A, Alapati K, Murthy A, Savithri HS, Murthy MR.
    J Struct Biol. 2016, 193: 95-105
35. Intracellular delivery of antibodies by chimeric Sesbania mosaic virus (SeMV) virus like particles.
    Abraham A, Natraj U, Karande AA, Gulati A, Murthy MR, Murugesan S, Mukunda P, Savithri HS.
    Sci Rep. 2016, Feb 24;6:21803. doi: 10.1038/srep21803.
36. Biodistribution and toxicity evaluation of sesbania mosaic virus nanoparticles in mice. 
    Vishnu Vardhan GP, SavithriHS,  Murthy MRN, Hema M. Archiv.
    Virol, 2016. DOI 10.1007/s00705-016-2958-9
37. Crystal structure of a thiolase from Escherichia coli at 1.8 A resolution
    Ithayaraja M, Janardan N, Wierenga RK, Savithri HS and Murthy MRN,
    Acta Cryst F72, 534–544, 2016.
38. Structural and Biochemical Investigations on the Catalytic Mechanism of Pyridoxal Kinase (PdxK) from Salmonella Typhimurium and its Interactions with PLP-Dependent Enzymes
    G. Deka, J. Benazir,  J. Kalyani, H.S. Savithri and M.R.N. Murthy
    Biophysical Journal. 110. 548a. 10.1016/j.bpj.2015.11.2930, 2016.
39. Connecting Active-Site Loop Conformations and Catalysis in Triosephosphate Isomerase: Insights from a Rare Variation at Residue 96 in the Plasmodial Enzyme
    Pareek V, Samanta M, Joshi NV, Balaram H, Murthy MR, Balaram P.
    Chembiochem 2016 Apr 29;17(7):620-9. Epub 2016 Feb 29.
40. Determination  of crystal  structures  of  proteins  of  unknown identity  using  a  marathon molecular-replacement  procedure: structure of  Stenotrophomonasmaltophilia phosphate-binding protein.
    Hatti K, Gulati A, Srinivasan N, Murthy MRN
    Acta Cryst., D72, 1081-1089 (2016).
41. Molecular dynamics studies on the domain swapped Salmonella typhimurium survival protein SurE: insights on the possible reasons for catalytic cooperativity
    Yamuna Kalyani Mathiharan & M.R.N. Murthy
    Journal of Biomolecular Structure and Dynamics doi/abs/10.1080/07391102.2017.1351400. (2017)
42. Structure determination of contaminant proteins using MarathonMR procedure.
    Hatti K, Biswas A, Choudary S, Reddy V, Sekar K, Srinivasan N, Murthy MRN
    J. of Str. Biology; JSB (2017). 3, 372-378 (*Cover page issue*)
43. Determination of crystal structures of proteins of unknown identity using a marathon molecular-replacement procedure: structure of Stenotrophomonas maltophilia phosphate-binding protein,
    Hatti K, Srinivasan N, Murthy MRN
    Acta Crystallographica Section D Structural Biology, doi:10.1107/s2059798316012419. 2017
44. Seeing is not believing: structure of glycerol dehydrogenase initially assumed to be structure of survival protein from Salmonella typhimurium.
    Hatti K, Mathiharan YK, Srinivasan N, Murthy MRN
    Acta Cryst. (2017). D73, 609-617, 2017.
45. Structural studies on the decamericS. typhimurium arginine decarboxylase (ADC): pyridoxal 5′-phosphate binding induces conformational changes.
    G. Deka., S. R. Bharath., H.S. Savithri., Murthy, M.R.N. (2017).
    Biochemical and Biophysical Research Communications. Vol 490:4, 1362-1368.
46. Comparative structural and enzymatic studies on Salmonella typhimurium diaminopropionate ammonia lyase reveals the role of its unique structural features.
    Deka, G., Bisht, S., Savithri, H.S. and Murthy, M.R.N. (2017).
    J. Struct. Biol.202, 118-128.
47. Structural and biophysical characterization of Rv3716c, a hypothetical protein from Mycobacterium tuberculosis.
    A. Gopalan, G. Deka., H.S. Savithri, A. Raja, Murthy, M.R.N. (2017)
    Biochem. Biophys. Res. CommunDOI:10.1016/j.bbrc.2017.11.093).
48. Structural and Functional Characterization of Sesbania Mosaic Virus.
    Bakshi, Arindam & Vardhan, Vishnu & Hema, M & Murthy, Mathur &Savithri, Handanahal.
    Chapter (2017) Doi: 10.1007/978-981-10-5672-7_18.
49. Structural and biochemical studies on the role of Thr166 and Asp236 in the catalytic function of D-serine deaminase from Salmonella typhimurium.
    Deka, G. bharat, S.R., Savithri, H.S. and Murthy, M.R.N.
    Biochem. Biophys. Res. Comm., 504(1), 40-45. 2018.
50. Development of sesbania mosaic virus nanoparticles for imaging.
    Vardhan, Vishnu & Hema, M &Sushmitha, C &Savithri, Handanahal& Natraj, Usha & R. N. Murthy, M.
    Archives of Virology. 10.1007/s00705-018-4097-y. 2018.
51. Emerging Trends in the Development of Plant Virus-Based Nanoparticles and Their Biomedical Applications.
    Hema, M & Vardhan, Vishnu &Savithri, Handanahal & Murthy, M.R.N.
    (2019) 10.1016/B978-0-12-816328-3.00006-4.
52. Structural and functional studies on Salmonella typhimurium pyridoxal iinase (PrdxK): the first structural evidence for the formation of Schiff base with the substrate.
    Deka, G., Kalyani, J.N., Benezir, F., Sabharawal, P, Savithri, H.S. and Murthy, M.R.N. (2019)
    FEBS J. (under publication)