Previous appointments:

Associate Professor, Department of Biochemistry, Bose Institute (July 2015-November 2020)

Assistant Professor, Department of Biochemistry, Bose Institute (January 2011- July 2015)

Research Associate, Howard Hughes Medical Institute and Department of Biophysical Chemistry, Johns Hopkins University School of Medicine, Baltimore, Maryland (December 2005- January 2011)

Post-doctoral Fellow, Cornell University, Ithaca, New York (November 2004- November 2005)

Visiting Research Fellow, Hamburg Outstation, EMBL, Germany (July 2003- December 2003)


Research interests:

Understanding specificity and Plasticity in protein-protein interactions:

In the cellular milieu proteins constantly come in contact with numerous other proteins and macromolecules. Most of these encounters do not elicit any meaningful physiological response and therefore, are not specific. However, specific interactions between proteins is crucial for the cellular survival. Understandably, alteration in the proteins via mutations lead to change in their “interactome” leading to patho-physiological consequences. The broad goal of our lab is to decipher the structural basis behind the specificity of physiologically relevant interactions. To narrow down on this broad topic, we chose to work on the interactions in ubiquitination pathways, a post-translational modification process of proteins that regulate numerous cellular processes including transcription, proteostasis, localization, and signal transduction. Ubiquitination in cells require a concerted effort by three classes of enzymes, namely E1, E2, and E3; and these enzymes interact among themselves in a highly specific and at times in a promiscuous manner to ubiquitinate specific substrate protein(s) to initiate requisite physiological response(s). Our lab works on novel and diverse members from these enzyme classes to understand the basis of their specificity from a structural and biochemical point of view.


Address: Department of Biochemistry
Centenary Campus
Bose Institute
P-1/12 C.I.T. Scheme VII-M
Kolkata - 700054, India
E-Mail: ajit[at]
Phone: +91-33-25693335


Our laboratory employs structural , biophysical, biochemical, and computational tools to understand the atomic basis of specificity and plasticity in protein-protein interactions that spatio-temporally regulate conjugation of ubiquitin to various proteins in eukaryotes. Ubiquitination is a highly conserved and ubiquitous post-translational modification in eukaryotes that require concerted action of  three classes of enzymes, commonly referred as E1, E2 and E3.  Our laboratory works with representative members of each these classes of enzymes trying to understand their interaction with other partners. A few of our key findings are -

  • Intramolecular ubiquitination acts as a regulatory mechanism and is a common feature in E2s with extended tails:

        All E2 enzymes are characterized by the presence of a conserved catalytic domain referred as the UBC domain. Many of them also contains either additional domains or intrinsically disordered extended tails. We work on understanding the importance of these extended tails in a few of these E2s and have found that in many cases these acts as auto-regulatory regions to control the E2 activity.

  • Molecular details that govern E2-affinity of RING E3 ligases leading to specificity:

        It is long appreciated that E3s discriminate E2s on the basis of their differences in the interface. However, studying the role of specific E2 residues that constitute the ~500 Å2 E3-binding interface was not possible due to inherent low affinities between E3s and E2s. We used an unusual E3 ZNRF1 to show that E3s can differentiate E2s on the basis of their subtle structural differences. We also find that apparently unassuming structural differences between E2s play a crucial role in shaping their affinity towards diverse E3 ligases.

            1.47 Angstrom crystal structure of an E3 ligase bound to its E2 partner

  • Importance of the conserved tryptophan residue in imparting ligase activity in monomeric RING E3 ligases:

        Many of the RING E3s contain a conserved tryptophan residue in their E2 binding surface that is crucial for their ligase activity while many E3s lacking the tryptophan shows robust activity. Our research that involved extensive data mining as well as biochemical studies on multiple E3s and their mutants revealed that the tryptophan is absolutely essential only for monomeric E3s while dimeric do not essentially require it. Instead, presence of this tryptophan in dimeric RING E3s results in hyperactivity and makes dimerization redundant for their ligase activity. Our data suggested that during the course of evolution dimeric E3s lost the tryptophan to allow regulation of their activity through dimerization.

                    A model of evolution of RING E3 ligases and conservation of the Tryptophan residue


1.     Ajit B. Datta, Pinak Chakrabarti, H. S. Subramanya, and Pradeep Parrack (2001).Purification and crystallization of cII: An unstable transcription activator from phage l. Biochem. Biophys. Res. Comm. 288:997–1000.

2.     Ajit B. Datta , Siddartha Roy and Pradeep Parrack (2003). Disorder-order transition of lambda CII promoted by low concentrations of guanidine hydrochloride suggests a stable core and disordered C-terminal region. Eur. J. Biochem. 270:4439-4446

3.     Ajit B. Datta, Siddartha Roy and Pradeep Parrack (2005). Role of the C-terminal region of CII protein in its oligomerization and activity. J. Mol Biol. 345(2):315 -24.

4.     Lalita Das, Ajit B. Datta , Suvroma Gupta, Asim Poddar, Suparna Sengupta, Mark E. Janik, and Bhabatarak Bhattacharyya (2005). -NH-dansyl isocolchicine exhibits a significantly improved tubulin-binding affinity and microtubule inhibition in comparison to isocolchicine by binding tubulin through its A and B rings. Biochemistry 44(9):3249 -58.

5.     Ajit B. Datta, Santosh Panjikar, Manfred Weiss, Pinak Chakrabarti and Pradeep Parrack (2005). Structure of Lambda CII: Implications for recognition of direct repeat DNA by an unusual tetrameric organization. Proc. Natl. Acad. Sci. USA 102(32):11242 -7.

6.     Man-Hee Suh, Ping Ye, Ajit B Datta, Mincheng Zhang and Jianhua Fu (2005). An agarose-acrylamide composite native gel system suitable for separating ultra –large protein complexes. Anal Biochem. 343(1):166-75.

7.     Suvroma Gupta, Lalita Das, Ajit B. Datta , Asim Poddar, Mark E. Janik, and Bhabatarak Bhattacharyya (2006). Oxalone and lactone moieties of podophyllotoxin exhibit properties of both the B and C rings of colchicine in its binding with tubulin. Biochemistry. 45(20):6467-75.

8.     Sabyasachi Halder, Ajit B. Datta and Pradeep Parrack (2007). Probing the antiprotease activity of lambdaCIII, an inhibitor of the Escherichia coli metalloprotease HflB (FtsH). J Bacteriol. 189(22):8130-8.

9.     Dipak Dutta, Kaustav Bandopadhyay, Ajit B. Datta, Avijit Sardesai and Pradeep Parrack (2009). Properties of HflX, an enigmatic protein from Escherichia coli. J. Bacteriol. 191(7):2307-14.

10.  Ajit B. Datta, Greg L. Hura and Cynthia Wolberger (2009). The Structure and conformation of Lys-63 linked tetra-ubiquitin J. Mol. Biol. 392(5):1117-24.

11.  Pabitra K. Parua, Ajit B. Datta and Pradeep Parrack (2010). Specific hydrophobic residues in the alpha4 helix of lambdaCII are crucial for maintaining its tetrameric structure and directing the lysogenic choice. J. Gen. Virol. 91(1):306-12.

12.  Nadine L. Samara*, Ajit B. Datta*, Christopher E. Berndsen, Xiangbin Zhang, Tinting Yao, Robert Cohen & Cynthia Wolberger (2010). Structural insights into the assembly and function of the SAGA deubiquitinating module. Science 328(5981):1025-9. (published online on Apr 15, 2010). * contributed equally

13.  Kaustav Bandyopadhyay, Pabitra K. Parua, Ajit B. Datta & Pradeep Parrack (2010). Escherichia coli HflK and HflC can individually inhibit the HflB (FtsH)-mediated proteolysis of lambdaCII in vitro. Arch. Biochem. Biophys. 501(2):239-43.

14.  Kaustav Bandyopadhyay, Pabitra K. Parua, Ajit B. Datta, & Pradeep Parrack (2011). Studies on Escherichia coli HflKC suggest the presence of an unidentified λ factor that influences the lysis-lysogeny switch. BMC Microbiol. 11:34.

15.  CM Guzzo, CE Berndsen, J Zhu, V Gupta, A Datta, RA Greenberg, C Wolberger, MJ Matunis (2012). RNF4-dependent hybrid SUMO-ubiquitin chains are signals for RAP80 and thereby mediate the recruitment of BRCA1 to sites of DNA damage. Sci Signal. 5(253):ra88.

16.  N Chongdar, S Dasgupta, Ajit B Datta*, G Basu (2014). Preliminary X-ray crystallographic analysis of an engineered glutamyl-tRNA synthetase from Escherichia coli. Acta Crystallogr F Struct Biol Commun. 70(Pt 7):922-7.

17.  D Mukherjee, Ajit B Datta, P Chakrabarti (2014). Crystal structure of HlyU, the hemolysin gene transcription activator, from Vibrio cholerae N16961 and functional implications. Biochim Biophys Acta. 1844:2346-2354.

18.  A Saha, J Mukhopadhyay, Ajit B Datta, P Parrack (2015). Revisiting the mechanism of activation of cyclic AMP receptor protein (CRP) by cAMP in Escherichia coli: Lessons from a subunit-crosslinked form of CRP. FEBS Lett. 589:358-63.

19.  N Chongdar, S DasGupta, Ajit B Datta, G Basu (2015) Dispensability of zinc and the putative zinc-binding domain in bacterial glutamyl-tRNA synthetase. Biosci Rep. 35(2). pii: e00184.

20.  A Mondal, R Chattopadhyaya, Ajit B Datta, P Parrack.(2015) Crystallization and X-ray analysis of the transcription-activator protein C1 of bacteriophage P22 in complex with the PRE promoter element. Acta Cryst. F 71(Pt 10):1286-91.

21.  P.A. Banka, AP Behera, S Sarkar, Ajit B. Datta* (2015). E3 catalyzed self-ubiquitination attenuates the activity of Ube2E ubiquitin conjugating enzymes. J. Mol. Biol. 427 (13): 2290–2304.

22.  A. DiBello, Ajit B. Datta, X Zhang, C Wolberger (2016). Role of E2-RING Interactions in Governing RNF4-Mediated Substrate Ubiquitination. J. Mol. Biol. 428(23):4639-4650.

23.  AP Behera, P Naskar , S. Agrawal, P.A. Banka, Ajit B. Datta* (2018). Structural insights into the nanomolar affinity of RING E3 ligase ZNRF1 for Ube2N and its functional implications. Biochem J. 475(9):1569-1582.

24.  S Sarkar, P. Borar, AP Behera, P.A. Banka, Ajit B. Datta* (2019). Designing active RNF4 monomers by introducing a tryptophan: avidity towards E2Ub conjugates dictates the activity of ubiquitin RING E3 ligases. Biochem J. 476(10):1465-1482.

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  • Intermediate Fellow, Wellcome Trust-DBT India Alliance, 2011
  • Ramanujan Fellow, Dept. of Science and Technology, India, 2010
  • INSA Young Scientist, Indian National Science Academy, India, 2006
  • Prof. B.B. Biswas Outstanding Student, Bose Institute, 2003
  • UNESCO-TWAS Short term Fellow, 2003


PhD Course work:

  • Macromolecular X-ray Crystallography,
  • Biochemistry (partial)

Integrated M.Sc.-PhD

  • Biophysical Chemistry Semester-I ( Coordinator and Instructor)
  • Biophysical Chemistry Special paper Semester -III (X-ray crystallography and Fluorescence Spectroscopy)


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Past Members:

  • Dr. Prerana Agarwal Banka (Ph.D awarded 2018)
  • Dr. Adaitya Prasad Behera (Ph.D. awarded 2019)
  • Dr. Sayani Sarkar (Ph.D. awarded 2020)
  • Dr. Shreyasi Dutta (DST -NPDF, 2017-2019)
  • Dr. Shubhangi Agarwal (M.Sc. Dessertation, 2012)

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