Smita Mohanty
Associate Professor
Biochemistry


Department of Chemistry and Biochemistry

Auburn University

Auburn, AL 36849-5312

Phone:  334-826-7980

mohansm@auburn.edu




University of Delhi, India, Ph.D., 1988

University of Washington, Seattle, WA, Postdoctoral Research Associate, 1991-1993

Albert Einstein College of Medicine, NY, Postdoctoral Research Associate, 1997-1998

State University of New York at Stony Brook, NY, Assistant Professor (Research), 1999-2005

Auburn University, Auburn, AL, Associate Professor (tenure-track), 2005-2011

Auburn University, Auburn, AL, Associate Professor (tenured), 2011-Present.



PECASE (Presidential Early Career Award for Scientist and Engineers) – 2000.

POWRE award from NSF-October 2000

Executive Editor,  Biochemistry & Physiology: Open Access (2011-Present).
(http://www.omicsgroup.org/journals/editorialboardBCP.php)

Editor. Special Issue on Structure and Function of Protein, Biochemistry & Physiology: Open Access http://www.omicsgroup.org/journals/ArchiveBCP/specialissue-biochemistry-physiology-open-access-S2.php

Editorial Article for the Special Issue: Structure and Function of Protein, Smita Mohanty, Biochem Physiol, S2:e001. doi: 10.4172/2168-9652.S2-e001 (2013).

Editorial Board Member, JSciMed Chemistry, 2013
(http://www.jscimedcentral.com/Chemistry/editors.php)

Editorial Board Member, Journal of Metabolomics & Systems Biology, Open Access, 2013(http://www.avensonline.org/biotechnology/metabolomics-systems-biology/editorial-board-26)



Biochemistry, Structural Biology, Molecular Biology, and Computational Chemistry:  
Cloning, expression, purification and 3-dimensional structure determination of proteins by NMR and X-ray crystallography, mutagenesis and functional studies of proteins involved in cancer, various signaling pathways and many diseases.

Research Summary

Our research interest has focused on structure-function studies of proteins using high-resolution solution NMR, circular dichroism (CD) and fluorescence spectroscopy techniques. It is amazing to see the relationship between the primary sequence of a protein to its 3-dimensional structure that defines specificity as well as diversity in its functions and how even a point mutation can sometimes disrupt or modify the functions of a protein causing in many instances abnormalities or diseases. To get a view of protein structure, function and mode of interactions at a molecular level, we use high resolution solution NMR, circular dichorism (CD), fluorescence techniques along with biochemical, molecular biology (cloning, mutagenesis) and computational chemistry.

Thus molecular biology, biochemistry, protein chemistry, biophysical chemistry (NMR and other techniques) and computational chemistry are used in our laboratory to understand and correlate the structure-functions of both soluble and membrane bound proteins. Several projects are currently in progress in our laboratory. Research work in our laboratory is supported by funding from NSF, USDA and NIH.

Congenital Disorders of Glycosylation

We are investigating the molecular mechanisms of function of an extremely important eukaryotic membrane bound enzyme “oligosaccharyltransferase (OST)”. Oligosaccharyltransferase is a membrane associated multimeric enzyme located in the endoplasmic reticulum (ER) and is involved in co-translational N-linked glycosylation of nascent protein. Genetic defects in OST cause a series of clinical problems known as congenital disorders of glycosylation (CDG) that includes mental retardation, developmental delay, hypoglycemia, dysmorphic features, anorexia etc. Complete loss is lethal for all animals. Our group is actively involved in the structure-function studies of both yeast and human Oligosaccharyltransferase enzymes. The 3-dimensional structures of proteins are essentially “blueprints” for the development of a chemical compound to be a successful drug. Our group has already solved the 3-dimensional solution structure of the first eukaryotic yeast OST subunit, Ost4p (shown below).

figure 2
(A) Stereo view of the ensemble of the 20 lowest energy NMR structures of Ost4p (B) Ribbon view of the structure of Ost4p. (C) Ost4p structure in membrane (D) Structure of Ost4p from the restricted molecular dynamics calculation in a water/octane/water simulation cell. Octane molecules in grey, water molecules in red and white. (E) Location of the mutation-sensitive residues on the helix a2, viewed along the helix axis. (F) Model of Stt3p-Ost4p-Ost4p complex 

Moreover, we have cloned, successfully overexpressed, and purified the most critical OST subunit, Stt3p. Structural and functional characterization of Stt3p containing the catalytic site of OST enzyme along with that of other yeast and human OST subunits is in progress in our laboratory. These studies will provide insight into the mechanisms of function of this essential and critical enzyme.

Human PDZ domain and Tumorigenesis

Glutaminase-interacting protein (GIP) is a small 14 kDa protein containing a single PDZ domain. GIP was originally identified in a yeast two-hybrid genetic selection system in human brain while looking for interactors of glutaminase. GIP is directly involved in the modulation of tumor growth through regulation of glutaminase and b-catenin. In addition, we have found that GIP interacts with the cell surface protein FAS, which belongs to tumor necrosis factor (TNF) receptor family and mediates cell apoptosis. Apart from glutaminase, b-catenin and FAS, a plethora of binding partners has been reported implicating GIP in key biological processes. Indeed, all the signal transduction pathways involving GIP can lead to cancer when unregulated. Interestingly, GIP regulates many of these signaling processes through its PDZ domain. Because PDZ proteins have well-defined binding sites, they are promising targets for drug discovery. Furthermore, GIP is one of the smallest members of the PDZ family, containing only one PDZ domain that represents its full primary structure, thus offering it as a very suitable candidate for structural studies. Structure, function, and interaction studies of GIP with different binding partners will provide us the insight into the mechanisms of action of this multifunctional protein, which is indeed a necessary prelude for successful drug design. Our investigation into structure, function, kinetics, dynamics, and interaction studies of GIP with different binding partners will provide the insight into the mechanisms and role of this PDZ domain containing human protein plays in recognition, signaling and tumorigenesis, which is essential for successful drug design.

figure 3
3D Model of GIP  

Signal Transduction in Olfaction

We have made great progress in understanding the mechanisms of odor detection in lepidopteran moth by the olfactory receptor using the proteins of “smell” or odorant binding protein (OBP). Our solution NMR structure of an OBP revealed the details of the odorant-binding site and provided the first insight into the nature of the odor uptake mechanism at neutral pH. Moreover, from the NMR structure of this protein at acidic pH, we reported a novel mechanism of odor release, triggered by the protonation of key histidine residues near the olfactory neuron where the membrane potential decreases the local pH. Our current research efforts are focused to test the above model of ligand release by mutational studies and to address the question of molecular recognition and mechanisms of substrate specificity by OBPs of different moth species.

figure 4  ApolPBP Binding cavity




















ApolPBP acetate binding site



Sevil Zencir, Monimoy Banerjee, Melanie J. Dobson, Ferhan Ayaydin, Elfrieda Ayaydin Fodor, Zeki Topcu and Smita Mohanty, New partner proteins containing novel internal recognition motif for human Glutaminase Interacting Protein (hGIP), Biochem. Biophys. Res. Commun. 432 (1),10-15 (2013).

*Dr. Zeki Topcu received Fulbright Scholarship and worked in Dr. Smita Mohanty's laboratory between 2009-2010.

Uma V. Katre, Suman Mazumder, and Smita Mohanty, Structural insights into the ligand binding and releasing mechanism of Antheraea polyphemus PBP1: role of the C-terminal tail, Biochemistry, 52, 1037-1044 (2013).

Monimoy Banerjee, David Zoetewey, Mohiuddin Ovee, Suman Mazumder, Valery Petrenko, Tatiana Samoylova and Smita Mohanty, Specificity and Promiscuity in human Glutaminase Interacting Protein (GIP) recognition: Insight from the binding of internal and C-terminal motif, Biochemistry, 51 (35), 6950–6960 (2012).

Chengdong Huang, Rajgopalan Bhaskaran and Smita Mohanty, Eukaryotic N-glycosylation Occurs Via membrane-anchored C-terminal domain of Stt3p subunit of oligosaccharyl transferase, Journal of Biological Chemistry, 287 (39), 32450-32458, (2012).

Smita Mohanty, Moth Olfaction: A Model of Exquisite Sensitivity and Specificity. Biochem Physiol 1:e106. doi:10.4172/bcpc.1000e106 (2012). (http://www.omicsgroup.org/journals/ArchiveBCP/articleinpressBCP.php).

Amit Kumar*, Priscilla Ward, Uma Katre and Smita Mohanty, A Novel Method of Production and Biophysical Characterization of a Mini-Membrane protein, Ost4p:  A Subunit of Yeast Oligosaccharyl Transferase, Biopolymers, 97, 499-507, (2012).*A. Kumar is a high school student, joined NYU in the fall of 2012).

Sevil Zencir, Mohiudeen Ovee, Melanie Donson, Monimoy Banerjee, Zeki Topcu and Smita Mohanty, Identification of brain-specific angiogenesis inhibitor 2 as an interaction partner of glutaminase interacting protein, Biochem. Biophys. Res. Commun. 411,792-797 (2011).

Janarthanan Krishnamoorthy and Smita Mohanty, Open-ITC: An alternate computational approach to analyze the ITC data of complex binding mechanisms, Journal of Molecular Recognition, 24, 1056-1066 (2011).

David Zoetewey, Mohiuddin Ovee, Monimoy Banerjee, Rajgopalan Bhaskaran and Smita Mohanty, Promiscuous binding at the crossroads of numerous cancer pathways: Insight from the binding of GIP with glutaminase L, Biochemistry, 50, 3528-3539, (2011).

Chengdong Huang and Smita Mohanty, Challenging the Limits: NMR Assignment of a 31 kDa Helical Membrane Protein, Journal of American Chemical Society2010, 132 (11),3662–3663.

Chengdong Huang, Smita Mohanty and Monimoy Banerjee, A Novel Method of Production and Biophysical Characterization of the Catalytic Domain of Yeast Oligosaccharyl Transferase,Biochemistry2010, 49, 1115-1126.

Uma V. Katre, Suman Mazumder, Rabi K. Prusti, and Smita Mohanty, Ligand Binding Turns Moth Pheromone-binding Protein into a pH Sensor: Effect On The Antheraea Polyphemus PBP1 Conformation,  Journal of Biological Chemistry ,  2009 , 284 (46), 32167-32177.

Monimoy Banerjee, Chengdong Huang, Javier Marquez, and Smita Mohanty, Probing the structure, function and dynamics of human gulataminase-interacting protein (GIP): A possible target for drug design, Biochemistry2008, 47 (35), 9208-9219.

Monimoy Banerjee, Erich Meyerowitz, Chengdong Huang & Smita Mohanty, Probing the Conformation and Dynamics of Allatostatin Neuropeptides: A Structural Model for Functional Differences, Peptides2008, 29(3):375-385.

Priscilla Ward, Chengdong Huang, Monimoy Banerjee & Smita Mohanty, Interaction of Metal Ions with Glutaminase Interacting Protein (GIP): A Potential Role of GIP in Brain Diseases,Spectroscopy2008, Volume 22, No. 4, page 213-221

Joshua Ring, Rabi K. Prusti & Smita Mohanty, Chemical Communication: A visit with insects,Current Chemical Biology2008, 2, Number 1, 83-96.

S. Zubkov, A. Gronenborn, I. L. Byeon & S. Mohanty, Structural consequences of the pH-induced conformational switch in A. polyphemus pheromone-binding protein: mechanisms of ligand release, Journal of Molecular Biology2005, 354, 1081-1090.

S. Mohanty, S. Zubkov & A. Gronenborn, Solution NMR structure of Antheraea polyphemus PBP provides new insight into pheromone recognition by pheromone binding proteins, Journal of Molecular Biology2004, 337, 443-451.

S. Zubkov, W. J. Lennarz & S. Mohanty, Structural basis for the function of a novel minimembrane protein subunit of yeast oligosaccharyltransferase Proc. Natl. Acad. Sci. U.S.A2004 101, issue 11, 3821-3826.

Smita Mohanty, Sergey Zubkov and Ramon Campos-Olivas, 1H, 13C and 15N backbone assignments of the pheromone binding protein from the silk moth Antheraea polyphemus (ApolPBP). J. Biomol. NMR2003, 27, 393.

Last updated: 11/11/2013