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Nitin Jain

Contact Info

Natin JainNitin Jain
Associate Professor, BCMB

Office: Mossman 411, (865-974-4045)
Lab: Mossman 441A

Ph.D. Physical Chemistry, Brandeis University, Waltham MA

Research Statement

My laboratory is primarily interested in application of biochemical and biophysical approaches for elucidation of Structure/Dynamics-Function relationships in biomolecules. Owing to the diverse nature of biological problems investigated, we utilize techniques from wide-ranging areas in biology such as molecular biology, cell biology, protein biochemistry, structural and computational biology. We currently have two active areas of research:

Functional dynamics of cytochrome P450 enzymes.
The cytochrome P450 family of enzymes in humans plays an important role in metabolism of greater than 90% of pharmaceutical drugs out in the market. We are interested in elucidation of functional dynamics in several important human and bacterial P450s that can help us understand why people metabolize drugs differently and why different people exhibit a variable spectrum of adverse drug effects. Results from such studies can immensely benefit pharmaceutical research, leading to better drug design and help prevent potentially lethal drug-drug interactions in wide-ranging diseases conditions (such as cancer, autoimmune diseases, cardiovascular diseases etc.) where these drugs are administered. Additionally, we are interested in structural and dynamic characterization of several commercially relevant bacterial P450s to identify mechanisms inherent to these proteins in terms of their specific substrate binding and chemical properties. An understanding of these will help in design of more efficient biocatalysts for novel chemical reactions.

Molecular basis of endotoxin recognition by receptors involved in the innate immune system.

Recognition of endotoxins released by microbial pathogens during infection of higher organisms leads to an appropriate host innate immune response. This response if uncontrolled, often leads to sepsis and septic shock, a major cause of mortality in hospitals. Onset of sepsis occurs in a series of signaling steps, initiated by binding of endotoxins to a key host cell receptor CD14 expressed on the surface of monocytes and tissue macrophages of the host. Efforts in our laboratory are focused on a precise understanding of the molecular mechanism underlying CD14-dependent endotoxin recognition and signaling, mainly using site-directed mutagenesis, cell-based functional assays and spectroscopic techniques. Insights gained from these studies will be quite useful in the design of effective antagonists and development of new strategies for prevention and therapeutic treatment of sepsis as well as infectious diseases.

Selected Publications

Liu Z, Lemmonds S, Huang J, Tyagi M, Hong L and Jain NU “Entropic contribution to enhanced thermal stability in the thermostable P450 CYP119” (2018) Proceedings of the Natural Academy of Sciences, 115 (43) E10049-E10058

Hong L, Jain NU, Cheng X, Bernal-Gomez A, Tyagi M, and Smith JC “Determination of functional collective motions in a protein at atomic resolution using coherent neutron scattering” (2016), Science Advances 2(10).

Miao Y, Yi Z, Glass D, Cantrell C, Baudry J, Jain NU and Smith JC “Coupled Flexibility Change in Cytochrome P450cam Determined by Neutron Scattering, NMR and Molecular Dynamics Simulation”  (2012) Biophys. J, 103: 2167-2176.

Miao Y, Yi Z, Glass D, Hong L, Tyagi M, Baudry J, Jain NU and Smith JC “Temperature-dependent dynamical transitions of different classes of amino acid residue in a globular protein” (2012) J. Am. Chem. Soc., 134: 19576-19579.

Albright S, Agrawal P and Jain NU “NMR spectral mapping of Lipid A molecular patterns affected by interaction with the innate immune receptor CD14” (2009) Biochem Biophys Res Commun, 378: 721-726.

Zhang W, Pochapsky SS, Pochapsky TC and Jain NU “Solution NMR structure of putidaredoxin-cytochrome P450cam complex via a combined residual dipolar coupling-spin labeling approach suggests a role for Trp106 of putidaredoxin in complex formation” (2008) J. Mol. Biol. 384(2): 349-363.