Sanchita Hati Professor Office: Phillips-445 Phone: 715 836 3850 Email: hatis at uwec dot edu

       Education

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Teaching Interests
 

• Biophysical Chemistry
• Biochemistry
• General Chemistry

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Research Interests

To Investigate the Interplay between Protein Dynamics and Function

To Classify and Characterize Proteins based on their Intrinsic Dynamics
 

Investigation of roles of  local and global motions on the enzymatic function of aminoacyl-tRNA synthetases (AARSs)  My research is focused on the simple question - how protein motions influence substrate binding and catalysis. The relationship between protein dynamics and its key functions (such as allosterism and catalysis) is an evolving perspective in enzymology. The more complex is the architecture of a multi-domain protein, the fuzzier is the picture at the molecular-level. For the past several years, my research group has been investigating the interplay of protein dynamics and enzymatic processes in the multi-domain enzyme systems - aminoacyl-tRNA synthetases (AARSs). Using computations and experiments, my research group is exploring how the global dynamics and local fluctuations modulate substrate recognition, catalysis, and allosteric communication in these multi-domain enzymes. Characterization of proteins based on their intrinsic dynamics It is increasingly recognized that protein dynamics play an important role in molecular recognition and catalytic activity. As the mobility of a protein is an intrinsic property that is encrypted in its primary structure, my research students and students of biophysical chemistry course are involved in i) classifying proteins based on their intrinsic dynamics and ii) examining if it is possible to characterize the function of a new protein based on its intrinsic mobility pattern. Investigation of the impact of macromolecular crowding on the conformational ensembles of AARSs Macromolecular crowding in the cytosolic environment influence substrate binding affinity and enzymatic activity of proteins. However, the mechanism of dynamic changes that occur during substrate binding and catalysis in the presence of macromolecules has remained under-explored for modular enzymes. Currently, we are investigating the impact of macromolecular crowding on the conformational dynamics of an AARS. We are using synthetic crowding agents to mimic cytosolic crowding conditions and have employed a hybrid compuational-experiemental approach (molecular simulations, intrinsic tryptophan fluorescence measurements, and enzyme kinetics) to probe the conformational-shift in the presence of crowding agents.

 
 

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Grants and Fellowships

NIH Academic Research Enhancement Award, 2015

NIH Recovery Act Administrative Supplement Award, 2010

NIH Academic Research Enhancement Award, 2008

Research Corporation Cottrell College Science Award, 2006

Graduate Research Fellowship, Indian Association for the Cultivation of Science, India, 1991

Lectureship and Research Fellowship Award in Chemistry, University Grant Commission, India, 1991

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Recent Publications
 

46. Polyethylene Glycol 20k. Does it Fluoresce?
B. Laatsch *, M. Brandt *, B. Finke *, C. J. Fossum  *, M. J. Wackett *, H. R. Lowater *, A. Narkiewicz-Jodko *, C. N. Le*,  T. Yang,  E. M. Glowgowski,  S. C. Bailey-Hartsel, S. Hati, S. and S. Bhattacharyya, (2023)  ACS Omega, 8, 14208–14218. (DOI:10.1021/acsomega.3c01124)

45. Evolution of Stronger SARS-CoV-2 Variants as Revealed Through the Lens of Molecular Dynamics Simulations
A. J. Wozney *, M. A. Smith *, M. Abdrabbo *, C. M. Birch *, K. A. Cicigoi *, C. C. Dolan *, A. E. L. Gerzema *, A. Hansen *, E. J. Henseler *, B. LaBerge *, C. M. Leavens *, C. N. Le *, A. C. Lindquist *, R. K. Ludwig *, M. G. O'Reilly ,* J. H. Reynolds *, B. A. Sherman *, H. W. Sillman *, M. A. Smith *, M. J. Snortheim ,* L. M. Svaren *, E. C. Vanderpas *, M. J. Wackett *, M. M. Wwiss *, Hati, S. and Bhattacharyya, S.(2022)   Protein J.,  41 , 444-456. (DOI: 10.1007/s10930-022-10065-6)

44. Pre-Existing Oxidative Stress Creates a Docking-Ready Conformation of the SARS-CoV-2 Receptor-Binding Domain
C. J. Fossum *, B. F. Laatsch *, H. R. Lowater *, A.  Narkiewicz-Jodko*,  L. Lonzarich *, S. Hati and S. Bhattacharyya (2022) ACS Bio & Med Chem Au , 2, 84-93. (DOI: 10.1021/acsbiomedchemau.1c00040)

43. Vitamin D and COVID-19: A Review on the Role of Vitamin D in Preventing and Reducing the Severity of COVID-19 Infection
M. Abdrabbo*, C. M. Birch*, M. Brandt*, K. A. Cicigoi*, S. J. Coffey*, C. C. Dolan*, H. Dvorak*, A. C. Gehrke*, A. E. L. Gerzema*, A. Hansen*, E. J. Henseler*, A. C. Huelsbeck*, B. LaBerge*, C. M. Leavens*, C. N. Le*, A. C. Lindquist*, R. K. Ludwig*, J. H. Reynolds*, N. J. Severson*, B. A. Sherman*, H. W. Sillman*, M. A. Smith*, M. A. Smith*, M. J. Snortheim*, L. M. Svaren*, E. C. Vanderpas*, M. J. Wackett*, A. J. Wozney*, S. Bhattacharyya, and S, Hati 2021)  Protein Science,  30 , 2206-2220. (DOI: 10.1002/pro.4190)

42.  Role of Oxidative Stress on SARS-CoV (SARS) and SARS-CoV-2 (COVID-19) Infection: A Review
S. Suhail *, Z. Zajac *, C. Fossum *, H. Lowater *, C. McCracken *, N. Severson *, B.  Laatsch *, A. Narkiewicz-Jodko *, B.  Johnson *, J. Liebau *, S. Bhattacharyya and S. Hati (2020) Protein J., 39,644-656.  (DOI: 10.1007/s10930-020-09935-8), 

41. Editing Domain Motions Preorganize the Synthetic Active Site of Prolyl-tRNA Synthetase
Q. H. Hu *, M. T. Williams *, I. Shulgina*,  C. Fossum*,  C.*, K. Weeks*,  L. A. Adams* ,  C. R. Reinhardt *, K.  Musier-Forsyth,  S. Hati, and S. Bhattacharyya, (2020) ACS Catal., 10,10229-10242.  (DOI:10.1021/acscatal.0c02381)

40.  Effects of Distal Mutations on Prolyl-Adenylate Formation of Escherichia coli Prolyl-tRNA Synthetase   J. Zajac*, H. Anderson*, L. Adams*, D. Wangmo*, S. Suhail*, A. Almen*, L. Berns*, B. Coerber*, L. Dawson*, A. Hunger*, J. Jehn*, J. Johnson*, N. Plack*, S. Strasser*, M. Williams*, S. Bhattacharyya, and S. Hati (2020) Protein J., 39, 542-553.  (DOI:10.1007/s10930-020-09910-3)

39.  Impact of Thiol-Disulfide Balance on the Binding of Covid-19 Spike Protein with Angiotensin-Converting Enzyme 2 Receptor
S. Hati   and S. Bhattacharyya, (2020) ACS Omega, 5, 16292-16298. (DOI:10.1021/acsomega.0c02125)

38. Crowder-induced Conformational Ensemble Shift in Escherichia Coli Prolyl-tRNA Synthetase.   L. A. Adams *, R. J. Andrews *, Q. H. Hu *, H. L. Smit *,  S. Hati, and S. Bhattacharyya, (2019)  Biophys. J.,  117, 1269-1284. (DOI:10.1016/j.bpj.2019.08.033)

37. Cyclic Changes in Active Site Polarization and Dynamics Drive the 'Ping-pong' Kinetics in NRH:Quinone Oxidoreductase 2: An Insight from QM/MM Simulations C. R. Reinhardt *, Q. H. Hu *, C. G. Bresnahan *, S. Hati, and S. Bhattacharyya, S. (2018)  ACS Catal.,  8, 12015-12029. (DOI: 10.1021/acscatal.8b04193)

36. Integrating Research into the Curriculum: A Low-Cost Strategy for Promoting Undergraduate Research S. Hati and S. Bhattacharyya, ACS Symposium Series "Best Practices for Supporting and Expanding Undergraduate Research in Chemistry" Eds. Gourley, B. L. and Jones, R. M. 2018, 119-141. (DOI:10.1021/bk-2018-1275.ch008)

35.  Investigation of Intrinsic Dynamics of Enzymes Involved in Metabolic Pathways using Coarse-grained Normal Mode Analysis.” S. Meeuwsen*; L. M. Adams*; A. N. Hodac*; R.D. McMunn*, A. S. Maxwell*, K. J. Carothers*, R. E. Egdorf*, P. M. Hanneman*, J. P. Kitzrow*, C. K. Keonigsberg*, O. Lopez-Martinez*, P. A. Matthew*, E. H. Richter*, J. E. Schenk*, H. L. Schmit*, M.A. Scott*, E. M. Volenec*, and Hati (2017) Cogent Biology, 3, 1291877

34.  Insight into the Kinetics and Thermodynamics of the Hydride Transfer Reactions between Quinones and Lumiflavin: A Density Functional Theory Study .C. R. Reinhardt,T. C. Jaglinski, A. M. Kastenschmidt, E. H.Song, A. K. Gross, A. J. Krause, J. M. Gollmar, ‎K. J. Meise, ‎Z. S. Stenerson, T. J. Weibel, A. Dison,‡ M. R. Finnegan, D. S. Griesi, ‎ M. D. Heltne, ‎T. G. Hughes, ‎C. D. Hunt, ‎K. A. Jansen, ‎ A. H. Xiong, S. Hati, and S. Bhattacharyya (2016) J.Mol. Model.,22, 199.

33. Incorporating modeling and simulations in undergraduate biophysical chemistry course to promote understanding of structure-dynamics-function relationships in proteins. S. Hati and S. Bhattacharyya (2016) Biochemistry and Molecular Biology Education, 44, 140-159.

32. Comparison of intrinsic dynamics of cytochrome P450 proteins using normal mode analysis. M. Dorner, R. McMunn, Students of Biophysical course, Fall 2013, and S. Hati (2015) Protein Science, 1495-1507.

31. Probing the global and local dynamics of aminoacyl-tRNA synthetases using all-atom and coarse-grained simulations.  A. M. Strom, S. C. Fehling, S. Bhattacharyya, and S. Hati (2014) J. Mol.  Model., 20,2235.

30.  Comparison of the intrinsic dynamics of aminoacyl-tRNA synthetases. N. Warren, A. Strom, B. Nicolet, K. Albin, J. Albrecht, B. Bausch, M. Dobbe, M. Dudek, S. Firgens, C. Fritsche, A. Gunderson, J. Heimann, C. Her, J. Hurt, D. Konorev, M. Lively, S. Meacham, V.Rodriguez, S.Tadayon, D. Trcka, Y. Yang, S. Bhattacharyya, and S. Hati (2014) Protein J. , 184-198.

29. Strictly conserved lysine of prolyl-tRNA synthetase editing domain facilitates binding and positioning of misacylated tRNAPro. T. G. Bartholow, B. L. Sanford, B. Cao, H. L. Schmit, J. M. Johnson, J. Meitzner, S. Bhattacharyya, K. Musier-Forsyth, and S. Hati (2014) Biochemistry, 53,1059-1068.

28. Multiple pathways promote dynamical coupling between catalytic domains in Escherichia coli prolyl-tRNA synthetase. J. M. Johnson, B. L. Sanford, A. M. Strom, S. N. Tadayon, B. P. Lehman, A. M. Zirbes, S. Bhattacharyya, K. Musier-Forsyth, and S. Hati (2013) Biochemistry, 52, 4399-4412.

27. Role of coupled motions in the catalytic activity of prokaryotic-like prolyl-tRNA synthetases. B. L. Sanford, B. V. Cao, J. M. Johnson, K. Zimmerman, A. M. Storm, R. M. Mueller, S. Bhattacharyya, K. Musier-Forsyth, and S. Hati (2012) Biochemistry, 51, 2146-2156.

26. Interplay of flavin's redox states and protein dynamics: an insight from QM/MM simulations of dihydronicotinamide riboside quinone oxidoreductase 2. R. M. Mueller, M. A. North, C. Yang, S. Hati, and S. Bhattacharyya (2011) J. Phys. Chem. B, 115, 3632-3641.

25. Evolutionary basis for the coupled-domain motions in Thermus thermophilus leucyl-tRNA synthetase. K. M. Weimer, B. L. Shane, M. Brunetto, S. Bhattacharyya, and S. Hati (2009) J. Biol. Chem., 284, 10088-99.

24. Restoring species-specific posttransfer editing activity to a synthetase with a defunct editing domain.  J. SternJohn, S. Hati, P. G. Siliciano, and K. Musier-Forsyth (2007) Proc. Natl. Acad. Sci. USA, 104, 2127-32.

23. Pre-transfer editing by class II prolyl-tRNA synthetase: role of aminoacylation active site in �selective release� of noncognate amino acids. S. Hati, B. Ziervogel, J. SternJohn, F. C. Wong, M. C. Nagan, A. R. Rosen, P. G. Siliciano, J. Chihade, and K. Musier-Forsyth (2006) J. Biol. Chem., 281, 27862-27872.