Krishnananda Chattopadhyay , Ph.D.

Senior Principal Scientist & HOD
Structural Biology & Bioinformatics
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Research Focus

Fluorescence correlation spectroscopy, protein folding, intrinsically disordered proteins, stability and aggregation of proteins

Research Interest

We use single molecules spectroscopy to study the folding, dynamics and aggregation of protein molecules in aqueous solution and inside live neuroblastoma cells. We have developed, for the first time, the applications of fluorescence correlation spectroscopy (FCS) to study microsecond fluctuations in protein molecules at single molecular resolution. Our group showed that a protein fluctuates between conformers of different radii, and these fluctuations (and not the structure alone) play key roles in defining its functions, folding and aggregation. Using alpha synuclein, a protein with strong implications in Parkinson’s disease (PD), we showed that these initial contacts can be correlated with subsequent oligomer formation and eventual formation of amyloid fibrils. Our work critically emphasizes on the importance of the early fluctuations towards developing small molecule aggregation inhibitors. Subsequently, our group used small molecules to coat magnetite nanoparticles for efficient inhibition of the early events of alpha synuclein aggregation. Using cytochrome c, we showed that these fluctuations affect the secondary function of apoptotic regulations of the protein. A highlight of this paper was written by a senior editor of Nature magazine for the June 2015 issue of Nature Chemical Biology.

Credentials

HOD, Structural Biology & Bioinformatics Division

  • Senior Scientist (2005-2006), Pfizer Global Biologics, St. Louis, USA
  • Research Associate (1999-2005), Washington University School of Medicine, St. Louis, USA ,
  • Ph.D, Tata Institute of Fundamental Research, 2000

Patents & Publications

PUBLICATIONS

  1.  Sarkar-Banerjee, Suparna; Chowdhury, Sourav; Sanyal, Dwipanjan; Mitra, Tulika; Roy, Sib Sankar; Chattopadhyay, Krishnananda;  The Role of Intestinal Fatty Acid Binding Proteins in Protecting Cells from Fatty Acid Induced Impairment of Mitochondrial Dynamics and Apoptosis . 2018 , Cellular Physiology and Biochemistry , 51 , 4 , 1658-1678
  2.  Chakraborty, Ritobrita; Sahoo, Sumit; Halder, Nyancy; Rath, Harapriya; Chattopadhyay, Krishnananda;  Conformational-Switch Based Strategy Triggered by [18] π Heteroannulenes toward Reduction of Alpha Synuclein Oligomer Toxicity.2018,ACS chemical neuroscience,in press,,
  3.  Tripathi, Timir; Chattopadhyay, Krishnananda;  Interaction of α-Synuclein with ATP Synthase: Switching Role from Physiological to Pathological.2018,ACS chemical neuroscience,in press,,
  4.  Nandi, Indrani; Chall, Sayantani; Chowdhury, Sourav; Mitra, Tulika; Roy, Sib Sankar; Chattopadhyay, Krishnananda;  Protein Fibril-Templated Biomimetic Synthesis of Highly Fluorescent Gold Nanoclusters and Their Applications in Cysteine Sensing . 2018 , ACS omega , 3 , 7 , 7703-7714
  5.  Sannigrahi, Achinta; Chall, Sayantani; Jawed, Junaid Jibran; Kundu, Amrita; Majumdar, Subrata; Chattopadhyay, Krishnananda;  Nanoparticle Induced Conformational Switch Between α-Helix and β-Sheet Attenuates Immunogenic Response of MPT63 . 2018 , Langmuir , 34 , 30 , 8807-8817
  6.  Mukherjee, Sayan; Hazra, Subhenjit; Chowdhury, Sourav; Sarkar, Soumen; Chattopadhyay, Krishnananda; Pramanik, Animesh;  A novel pyrrole fused coumarin based highly sensitive and selective fluorescence chemosensor for detection of Cu2+ ions and applications towards live cell imaging . 2018 , Journal of Photochemistry and Photobiology A: Chemistry , 364 , , 635-644
  7.  Ghosh, Sumanta; Kundu, Amrita; Chattopadhyay, Krishnananda;  Small Molecules Attenuate the Interplay between Conformational Fluctuations, Early Oligomerization and Amyloidosis of Alpha Synuclein . 2018 , Scientific reports , 8 , 1 , 5481
  8.  Sarkar-Banerjee, Suparna; Goyal, Sachin; Gao, Ning; Mack, John; Thompson, Benito; Dunlap, David; Chattopadhyay, Krishnananda; Finzi, Laura;  Specifically bound lambda repressor dimers promote adjacent non-specific binding . 2018 , PloS one , 13 , 4 , e0194930
  9.  Saha, Baishakhi; Chowdhury, Sourav; Sanyal, Dwipanjan; Chattopadhyay, Krishnananda; Suresh Kumar, Gopinatha;  Comparative Study of Toluidine Blue O and Methylene Blue Binding to Lysozyme and Their Inhibitory Effects on Protein Aggregation . 2018 , ACS Omega , 3 , 3 , 2588-2601
  10.  Chowdhury, S; Banerjee, A; Chattopadhyay, K;  Metal ion co-factors sculpt the heterogeneity of conformational landscape in Superoxide Dismutase . 2017 , EUROPEAN BIOPHYSICS JOURNAL WITH BIOPHYSICS LETTERS , 46 , , S344-S344
  11.  Ghosh, Sumanta; Chakraborty, Biprashekhar; Dey, Sandip; Biswas, Chiranjit; Chowdhury, Rukhsana; Chattopadhyay, Krishnananda; Sengupta, Jayati;  Electron microscopy reveals unique nano forms of bacterial spores . 2017 , bioRxiv , , , 228833
  12.  Chall, Sayantani; Mati, Soumya Sundar; Das, Indranee; Kundu, Amrita; De, Goutam; Chattopadhyay, Krishnananda;  Understanding the Effect of Single Cysteine Mutations on Gold Nanoclusters as Studied by Spectroscopy and Density Functional Theory Modeling . 2017 , Langmuir , 33 , 43 , 12120-12129
  13.  Singharoy, Dipti; Chowdhury, Sourav; Mati, Soumya Sundar; Ghosh, Swadesh; Chattopadhyay, Krishnananda; Bhattacharya, Subhash Chandra;  Photoinduced Electron Transfer Switching Mechanism of a Naphthalimide Derivative with its Solvatochromic Behaviour: An Experimental and Theoretical Study with In Cell Investigations . 2017 , Chemistry–A European Journal , 23 , 65 , 16516-16524
  14.  Kundu, Amrita; Ghosh, Sumanta; Chattopadhyay, Krishnananda;  Small Molecules Attenuate the Interplay between Conformational Fluctuations, Early Oligomerization and Amyloidosis of Alpha Synuclein . 2017 , bioRxiv , , , 177006
  15.  Sil, Pallabi; Paul, Simanta Sarani; Silvio, Eva Di; Travaglini-Allocatellib, Carlo; Chattopadhyay, Krishnananda;  Polymer-fabricated synthesis of cerium oxide nanoparticles and applications as a green catalyst towards multicomponent transformation with size-dependent activity studies . 2016 , PHYSICAL CHEMISTRY CHEMICAL PHYSICS , 18 , 35 , 24537-24548
  16.  Joshi, Nidhi; Mukhopadhyay, Anindita; Basak, Sujit; De, Goutam; Chattopadhyay, Krishnananda;  Surface Modification: Surface Coating Rescues Proteins from Magnetite Nanoparticle Induced Damage (Part. Part. Syst. Charact. 8/2013) . 2013 , Particle & Particle Systems Characterization , 30 , 8 , 647-647
  17.  Mukherjee, Manini; Ghosh, Ranendu; Chattopadhyay, Krishnananda; Ghosh, Sanjib;  Stepwise unfolding of a multi-tryptophan protein MPT63 with immunoglobulin-like fold: detection of zone-wise perturbation during guanidine hydrochloride-induced unfolding using phosphorescence spectroscopy . 2016 , RSC Advances , 6 , 66 , 61077-61087
  18.  Sil, Pallabi; Paul, Simanta Sarani; Di Silvio, Eva; Travaglini-Allocatelli, Carlo; Chattopadhyay, Krishnananda;  Studies of cytochrome c-551 unfolding using fluorescence correlation spectroscopy and other biophysical techniques . 2016 , Physical Chemistry Chemical Physics , 18 , 35 , 24537-24548
  19.  Kundu, Amrita; Kundu, Sangeeta; Chattopadhyay, Krishnananda;  The presence of non‐native helical structure in the unfolding of a beta‐sheet protein MPT63 . 2017 , Protein Science , 26 , 3 , 536-549
  20.  Sannigrahi, Achinta; Maity, Pabitra; Karmakar, Sanat; Chattopadhyay, Krishnananda;  Interaction of KMP-11 with phospholipid membranes and its implications in leishmaniasis: effects of single tryptophan mutations and cholesterol . 2017 , The Journal of Physical Chemistry B , 121 , 8 , 1824-1834
  21.  Kundu, Amrita; Ghosh, Sumanta; Chattopadhyay, Krishnananda;  The Effect of Small Molecules on Early and Late Events of Alpha Synuclein Aggregation in Solution and Inside Living Cells . 2016 , Biophysical Journal , 110 , 3 , 533a
  22.  Lahiri, Sagar; Banerjee, Shakri; Dutta, Trina; Sengupta, Shinjinee; Dey, Sandip; Roy, Rusha; Sengupta, Devlina; Chattopadhyay, Krishnananda; Ghosh, Anil K;  Enzymatic and Regulatory Attributes of Trehalose‐6‐Phosphate Phosphatase from Candida utilis and its Role During Thermal Stress . 2014 , Journal of cellular physiology , 229 , 9 , 1245-1255
  23.  Paramanik, Bipattaran; Kundu, Amrita; Chattopadhyay, Krishnananda; Patra, Amitava;  Study of binding interactions between MPT63 protein and Au nanocluster . 2014 , RSC Advances , 4 , 66 , 35059-35066
  24.  Mukherjee, Manini; Ghosh, Ranendu; Chattopadhyay, Krishnananda; Ghosh, Sanjib;  pH-induced structural change of a multi-tryptophan protein MPT63 with immunoglobulin-like fold: identification of perturbed tryptophan residue/residues . 2015 , Journal of Biomolecular Structure and Dynamics , 33 , 10 , 2145-2160
  25.  Sarkar-Banerjee, Suparna; Chowdhury, Sourav; Paul, Simanta Sarani; Dutta, Debashis; Ghosh, Anisa; Chattopadhyay, Krishnananda;  The Non-native Helical Intermediate State May Accumulate at Low pH in the Folding and Aggregation Landscape of the Intestinal Fatty Acid Binding Protein . 2016 , Biochemistry , 55 , 32 , 4457-4468
  26.  Joshi, Nidhi; Mukhopadhyay, Anindita; Basak, Sujit; De, Goutam; Chattopadhyay, Krishnananda;  Surface coating rescues proteins from magnetite nanoparticle induced damage . 2013 , Particle & Particle Systems Characterization , 30 , 8 , 683-694
  27.  Paul, Simanta Sarani; Sil, Pallabi; Chakraborty, Ritobrita; Haldar, Shubhasis; Chattopadhyay, Krishnananda;  Molecular crowding affects the conformational fluctuations, peroxidase activity, and folding landscape of yeast cytochrome c . 2016 , Biochemistry , 55 , 16 , 2332-2343
  28.  Basak, Sujit; Prasad, GV R Krishna; Varkey, Jobin; Chattopadhyay, Krishnananda;  Early Sodium Dodecyl Sulfate Induced Collapse of α-Synuclein Correlates with Its Amyloid Formation . 2014 , ACS chemical neuroscience , 6 , 2 , 239-246
  29.  Joshi, Nidhi; Basak, Sujit; Kundu, Sangeeta; De, Goutam; Mukhopadhyay, Anindita; Chattopadhyay, Krishnananda;  Attenuation of the early events of α-synuclein aggregation: a fluorescence correlation spectroscopy and laser scanning microscopy study in the presence of surface-coated Fe3O4 nanoparticles . 2015 , Langmuir , 31 , 4 , 1469-1478
  30.  Chattopadhyay, Krishnananda; Frieden, Carl;  Steady‐state and time‐resolved fluorescence studies of the intestinal fatty acid binding protein . 2006 , Proteins: Structure, Function, and Bioinformatics , 63 , 2 , 327-335
  31.  Haldar, Shubhasis; Sil, Pallabi; Thangamuniyandi, Muruganandan; Chattopadhyay, Krishnananda;  Conversion of amyloid fibrils of cytochrome c to mature nanorods through a honeycomb morphology . 2014 , Langmuir , 31 , 14 , 4213-4223
  32.  Basak, Sujit; Chattopadhyay, Krishnananda;  Fluorescence correlation spectroscopy study on the effects of the shape and size of a protein on its diffusion inside a crowded environment . 2013 , Langmuir , 29 , 47 , 14709-14717
  33.  Lahiri, Sagar; Basu, Arghya; Sengupta, Shinjinee; Banerjee, Shakri; Dutta, Trina; Soren, Dhananjay; Chattopadhyay, Krishnananda; Ghosh, Anil K;  Purification and characterization of a trehalase–invertase enzyme with dual activity from Candida utilis . 2012 , Archives of biochemistry and biophysics , 522 , 2 , 90-99
  34.  Sharma, Sunny; Pathak, Nikhil; Chattopadhyay, Krishnananda;  Osmolyte induced stabilization of protein molecules: a brief review.2013,Journal of Proteins & Proteomics,3,2,
  35.  Haldar, Shubhasis; Chattopadhyay, Krishnananda;  Effects of arginine and other solution additives on the self-association of different surfactants: An investigation at single-molecule resolution . 2011 , Langmuir , 27 , 10 , 5842-5849
  36.  Ghosh, Ranendu; Mukherjee, Manini; Chattopadhyay, Krishnananda; Ghosh, Sanjib;  Unusual optical resolution of all four tryptophan residues in MPT63 protein by phosphorescence spectroscopy: assignment and significance . 2012 , The Journal of Physical Chemistry B , 116 , 41 , 12489-12500
  37.  Sharma, Sunny; Sarkar, Suparna; Paul, Simanta Sarani; Roy, Syamal; Chattopadhyay, Krishnananda;  A small molecule chemical chaperone optimizes its unfolded state contraction and denaturant like properties . 2013 , Scientific reports , 3 , , 3525
  38.  Chattopadhyay, Krishnananda; Mazumdar, Shyamalava;  Direct electrochemistry of heme undecapeptide in aqueous surfactant solutions: the effect of hydrophobicity and axial ligation on redox potential of heme . 1997 , Current Science , , , 65-68
  39.  Sarkar, Suparna; Chattopadhyay, Krishnananda;  Studies of early events of folding of a predominately β-sheet protein using fluorescence correlation spectroscopy and other biophysical methods . 2014 , Biochemistry , 53 , 9 , 1393-1402
  40.  Paul, Simanta Sarani; Sil, Pallabi; Haldar, Shubhasis; Mitra, Samaresh; Chattopadhyay, Krishnananda;  Subtle change in the charge distribution of surface residues may affect the secondary functions of cytochrome c . 2015 , Journal of Biological Chemistry , , , jbc. M114. 607010
  41.  Chattopadhyay, Krishnananda; Mazumdar, Shyamalava;  Direct electrochemical oxidation of horseradish peroxidase: cyclic voltammetric and spectroelectrochemical studies . 1999 , New Journal of Chemistry , 23 , 2 , 137-139
  42.  Haldar, Shubhasis; Paul, Simantasarani; Joshi, Nidhi; Dasgupta, Anindya; Chattopadhyay, Krishnananda;  The presence of the iron-sulfur motif is important for the conformational stability of the antiviral protein, Viperin . 2012 , PLoS One , 7 , 2 , e31797
  43.  Basak, Sujit; Chattopadhyay, Krishnananda;  Studies of protein folding and dynamics using single molecule fluorescence spectroscopy . 2014 , Physical Chemistry Chemical Physics , 16 , 23 , 11139-11149
  44.  Chattopadhyay, Krishnananda; Das, Tapan Kanti; Majumdar, Ananya; Mazumdar, Shyamalava;  NMR studies on interaction of lauryl maltoside with cytochrome c oxidase: a model for surfactant interaction with the membrane protein . 2002 , Journal of inorganic biochemistry , 91 , 1 , 116-124
  45.  Mukhopadhyay, Anindita; Basak, Sujit; Das, Jugal Kishore; Medda, Samar Kumar; Chattopadhyay, Krishnananda; De, Goutam;  Ag− TiO2 Nanoparticle Codoped SiO2 Films on ZrO2 Barrier-Coated Glass Substrates with Antibacterial Activity in Ambient Condition . 2010 , ACS applied materials & interfaces , 2 , 9 , 2540-2546
  46.  Haldar, Shubhasis; Chattopadhyay, Krishnananda;  Interconnection of Salt-induced Hydrophobic Compaction and Secondary Structure Formation Depends on Solution Conditions REVISITING EARLY EVENTS OF PROTEIN FOLDING AT SINGLE MOLECULE RESOLUTION . 2012 , Journal of Biological Chemistry , 287 , 14 , 11546-11555
  47.  Frieden, Carl; Chattopadhyay, Krishnananda; Elson, Elliot L;  What fluorescence correlation spectroscopy can tell us about unfolded proteins . 2002 , Advances in protein chemistry , 62 , , 91-109
  48.  Chattopadhyay, Krishnananda; Zhong, Shi; Yeh, Syun-Ru; Rousseau, Denis L; Frieden, Carl;  The intestinal fatty acid binding protein: the role of turns in fast and slow folding processes . 2002 , Biochemistry , 41 , 12 , 4040-4047
  49.  Haldar, Shubhasis; Mitra, Samaresh; Chattopadhyay, Krishnananda;  The role of protein stabilizers on the conformation of the unfolded state of cytochrome c and its early folding kinetics: An investigation at single molecular resolution . 2010 , Journal of Biological Chemistry , , , jbc. M110. 116673
  50.  Sen, Tapasi; Mandal, Sadananda; Haldar, Shubhasis; Chattopadhyay, Krishnananda; Patra, Amitava;  Interaction of gold nanoparticle with human serum albumin (HSA) protein using surface energy transfer . 2011 , The Journal of Physical Chemistry C , 115 , 49 , 24037-24044
  51.  Ghosh, Ranendu; Sharma, Sunny; Chattopadhyay, Krishnananda;  Effect of arginine on protein aggregation studied by fluorescence correlation spectroscopy and other biophysical methods . 2009 , Biochemistry , 48 , 5 , 1135-1143
  52.  Chattopadhyay, Krishnananda; Mazumdar, Shyamalava;  Stabilization of partially folded states of cytochrome c in aqueous surfactant: effects of ionic and hydrophobic interactions . 2003 , Biochemistry , 42 , 49 , 14606-14613
  53.  Mukhopadhyay, Anindita; Joshi, Nidhi; Chattopadhyay, Krishnananda; De, Goutam;  A facile synthesis of PEG-coated magnetite (Fe3O4) nanoparticles and their prevention of the reduction of cytochrome C . 2011 , ACS applied materials & interfaces , 4 , 1 , 142-149
  54.  Chattopadhyay, Krishnananda; Saffarian, Saveez; Elson, Elliot L; Frieden, Carl;  Measuring unfolding of proteins in the presence of denaturant using fluorescence correlation spectroscopy . 2005 , Biophysical journal , 88 , 2 , 1413-1422
  55.  Chattopadhyay, Krishnananda; Mazumdar, Shyamalava;  Direct electrochemistry of heme proteins: effect of electrode surface modification by neutral surfactants . 2001 , Bioelectrochemistry , 53 , 1 , 17-24
  56.  Chattopadhyay, Krishnananda; Saffarian, Saveez; Elson, Elliot L; Frieden, Carl;  Measurement of microsecond dynamic motion in the intestinal fatty acid binding protein by using fluorescence correlation spectroscopy . 2002 , Proceedings of the National Academy of Sciences , 99 , 22 , 14171-14176
  57.  Chattopadhyay, Krishnananda; Elson, Elliot L; Frieden, Carl;  The kinetics of conformational fluctuations in an unfolded protein measured by fluorescence methods . 2005 , Proceedings of the National Academy of Sciences , 102 , 7 , 2385-2389
  58.  Chattopadhyay, Krishnananda; Mazumdar, Shyamalava;  Structural and conformational stability of horseradish peroxidase: effect of temperature and pH . 2000 , Biochemistry , 39 , 1 , 263-270