Raghavan Varadarajan

Strategy for purifying maltose binding protein fusion proteins by affinity precipitation (2008)

Raghava, Smita, Aquil, Samina, Bhattacharyya, Sanchari, Varadarajan, Raghavan, Gupta, Munishwar N

The maltose binding protein (MBP) affinity tag has been extensively used for protein purification. A commercial grade cationic starch could precipitateMBPor anMBP-tagged protein quantitatively by...

Stereochemical Criteria for Prediction of the Effects of Proline Mutations on Protein Stability (2007)

Kanika Bajaj, M. S. Madhusudhan, Bharat V. Adkar, Purbani Chakrabarti, C. Ramakrishnan, Andrej Sali, ...

When incorporated into a polypeptide chain, proline (Pro) differs from all other naturally occurring amino acid residues in two important respects. The ϕ dihedral angle of Pro is constrained to...

Stereochemical Criteria for Prediction of the Effects of Proline Mutations on Protein Stability (2007)

Kanika Bajaj, M.S. Madhusudhan, Bharat V Adkar, Purbani Chakrabarti, C Ramakrishnan, Andrej Sali, ...

When incorporated into a polypeptide chain, Proline (Pro) differs from all other naturally occurring amino acid residues in two important respects. The φ dihedral angle of Pro is constrained to...

Role of Stimuli-Sensitive Polymers in Protein Refolding: \alpha-Amylase and CcdB (Controller of Cell Division or Death B) as Model Proteins (2007)

Mondal, Kalyani, Raghava, Smita, Barua, Bipasha, Varadarajan, Raghavan, Gupta, Munishwar N

Alginate, a calcium-sensitive polymer, could carry out simultaneous purification and refolding of 8 M urea/100 mM dithiothreitol (DTT) denatured and thermally denatured R-amylase present in a...

Thermodynamic Effects of Proline Introduction on Protein Stability (2007)

Prajapati, Ravindra Singh, Das, Mili, Sreeramulu, Sridhar, Sirajuddin, Minhajuddin, Srinivasan, Sankaranarayanan, Krishnamurthy, Vaishnavi, ...

The amino acid Pro is more rigid than other naturally occurring amino acids and, in proteins, lacks an amide hydrogen. To understand the structural and thermodynamic effects of Pro substitutions, it...

Design and Isolation of Temperature-sensitive Mutants of Gal4 in Yeast and Drosophila (2007)

Mondal, Kajari, Dastidar, Antara Ghosh, Singh, Guramrit, Madhusudhanan, S, Gande, Santosh Lakshmi, VijayRaghavan, K, ...

Little is known about mechanisms responsible for the temperature-sensitive (ts) phenotype, or of the transferability of ts mutants of a specific gene between organisms. Using a structure-based...

Stereochemical Criteria for Prediction of the Effects of Proline Mutations on Protein Stability (2007)

Bajaj, Kanika, Madhusudhan, MS, Adkar, Bharat V, Chakrabarti, Purbani, Ramakrishnan, C, Sali, Andrej, ...

When incorporated into a polypeptide chain, proline (Pro) differs from all other naturally occurring amino acid residues in two important respects. The \phi dihedral angle of Pro is constrained to...

Design of Disulfide-linked Thioredoxin Dimers and Multimers Through Analysis of Crystal Contacts (2007)

Das, Mili, Kobayashi, Masanori, Yamada, Yusuke, Sreeramulu, Sridhar, Ramakrishnan, C, Wakatsuki, Soichi, ...

Disulfide bonds play an important role in protein stability and function. Here, we describe a general procedure for generating disulfide-linked dimers and multimers of proteins of known crystal...

Design and Utility of Temperature-Sensitive Gal4 Mutants for Conditional Gene Expression in Drosophila (2007)

Mondal, Kajari, VijayRaghavan, K, Varadarajan, Raghavan

Temperature-sensitive (ts) mutants are valuable tools to study the function of essential genes in vivo. Despite their widespread use, little is known about mechanisms responsible for the...

Contribution of Cation-\pi Interactions to Protein Stability (2006)

Prajapati, Ravindra S, Sirajuddin, Minhajuddin, Durani, Venuka, Sreeramulu, Sridhar, Varadarajan, Raghavan

Calculations predict that cation-\pi interactions make an important contribution to protein stability. While there have been some attempts to experimentally measure strengths of cation-\pi...

Design of immunogens that present the crown of the HIV-1 V3 loop in a conformation competent to generate 447-52D-like antibodies (2006)

Chakraborty, Kausik, Durani, Venuka, Roshan Miranda, Edward, Citron, Michael, Liang, Xiaoping, Schleif, William, ...

gp120 is a subunit of the envelope glycoprotein of HIV-1. The third variable loop region of gp120 (V3 loop) contains multiple immunodominant epitopes and is also functionally important for deciding...

Attempts to Delineate the Relative Contributions of Changes in Hydrophobicity and Packing to Changes in Stability of Ribonuclease S Mutants (2005)

Das, Mili, Rao, Bharathi Vasudeva, Ghosh, Sanjukta, Varadarajan, Raghavan

While the hydrophobic driving force is thought to be a majorcontributor to protein stability, it is difficult to experimentallydissect out its contribution to the overall free energy of folding....

NMR structural analysis of a peptide mimic of the bridging sheet of HIV-1 gp120 in methanol and water (2005)

Chakraborty, Kausik, Shivakumar, P, Raghothama, S, Varadarajan, Raghavan

gp120 is a subunit of the Env (viral envelope protein) of HIV-1. The protein consists of inner and outer domains linked by a bridging sheet. Several gp120 residues that bind the neutralizing antibody...

Mutagenesis-based definitions and probes of residue burial in proteins (2005)

Bajaj, Kanika, Chakrabarti, Purbani, Varadarajan, Raghavan

Every residue of the 101-aa Escherichia, coli toxin CcdB was substituted with Ala, Asp, Glu, Lys, and Arg by using site-directed mutagenesis. The activity of each mutant in vivo was characterized as...

Protein Minimization of the gp120 Binding Region of Human CD4 \dagger (2005)

Sharma, Deepak, Balamurali, MM, Chakraborty, Kausik, Kumaran, Sowmini, Jeganathan, Sadasivam, Rashid, Umar, ...

CD4 is an important component of the immune system and is also the cellular receptor for HIV-1. CD4 consists of a cytoplasmic tail, one transmembrane region, and four extracellular domains, D1-D4....

Protein Stabilization by Introduction of Cross-Strand Disulfides (2005)

Chakraborty, Kausik, Thakurela, Sudhir, Prajapati, Ravindra Singh, Indu, S, Ali, Shaik Syed P, Ramakrishnan, C, ...

Disulfides cross-link residues in a protein that are separated in primary sequence and stabilize the protein through entropic destabilization of the unfolded state. While the removal of naturally...

Characterization of gp120 and its Single-Chain Derivatives, $gp120-CD4_D_1_2$ and gp120-M9: Implications for Targeting the $CD4_i$ Epitope in Human Immunodeficiency Virus Vaccine Design (2005)

Varadarajan, Raghavan, Sharma, Deepak, Chakraborty, Kausik, Patel, Mayuri, Citron, Michael, Sinha, Prem, ...

Single-chain derivatives of JRFL gp120 linked to the first two domains of human CD4 $(gp120-CD4_D_1_2)$ or to the CD4 miniprotein analog CD4M9 (gp120-M9), have been constructed. Biacore studies...

Design of temperature-sensitive mutants solely from amino acid sequence (2004)

Chakshusmathi, Ghadiyaram, Mondal, Kajari, Lakshmi, Santosh G, Singh, Guramrit, Roy, Ankita, Babu, Ravindra Ch, ...

Temperature-sensitive (Ts) mutants are a powerful tool with which to study gene function in vivo. Ts mutants are typically generated by random mutagenesis followed by laborious screening procedures....

Thermodynamic characterization of monomeric and dimeric forms of CcdB (controller of cell division or death B protein) (2004)

Bajaj, Kanika, Chakshumathi, Ghadiyaram, Bachhawat-Sikder, Kiran, Surolia, Avadhesha, Varadarajan, Raghavan

The protein CcdB (controller of cell division or death B)is an Fplasmid-encoded toxin that acts as an inhibitor of Escherichia coli DNA gyrase. The stability and aggregation state of CcdB have been...

Thermodynamic Effects of Replacements of Pro Residues in Helix Interiors of Maltose-Binding Protein (2003)

Prajapati, RS, Lingaraju, GM, Bacchawat, Kiran, Surolia, Avadhesha, Varadarajan, Raghavan

Introduction of Pro residues into helix interiors results in protein destabilization. It is currently unclear if the converse substitution (i.e., replacement of Pro residues that naturally occur in...

A Procedure for Detection and Quantitation of Cavity Volumes in Proteins (2002)

Chakravarty, Suvobrata, Bhinge, Akshay, Varadarajan, Raghavan

Accurate identification of cavities is important in the study of protein structure, stability, design, and ligand binding. Identification and quantitation of cavities is a nontrivial problem because...

A procedure for detection and quantitation of cavity volumes in proteins. Application to measure the strength of the hydrophobic driving force in protein folding (2002)

Chakravarty, Suvobrata, Bhinge, Akshay, Varadarajan, Raghavan

Accurate identification of cavities is important in the study of protein structure, stability, design, and ligand binding. Identification and quantitation of cavities is a nontrivial problem because...

Elucidation of Factors Responsible for Enhanced Thermal Stability of Proteins: A Structural Genomics Based Study (2002)

Chakravarty, Suvobrata, Varadarajan, Raghavan

Understanding the molecular basis for the enhanced stability of proteins from thermophiles has been hindered by a lack of structural data for homologous pairs of proteins from thermophiles and...

Electron Spin Resonance and Fluorescence Studies of the Bound-state Conformation of a Model Protein Substrate to the Chaperone SecB (2001)

Panse, Vikram G, Beena, K, Philipp, Reinhard, Trommer, Wolfgang E, Vogel, Pia D, Varadarajan, Raghavan

SecB is a homotetrameric, cytosolic chaperone that forms part of the protein translocation machinery in Escherichia coli. We have investigated the bound-state conformation of a model protein...

Reversible formation of on-pathway macroscopic aggregates during the folding of maltose binding protein (2001)

Ganesh, C, Zaidi, Faisal N, Udgaonkar, Jayant B, Varadarajan, Raghavan

Maltose binding protein (MBP) is widely used as a model for protein folding and export studies. We show here that macroscopic aggregates form transiently during the refolding of MBP at micromolar...

Thermodynamics of Substrate Binding to the Chaperone SecB (2000)

Panse, Vikram G, Swaminathan, Chittoor P, Surolia, Avadhesha, Varadarajan, Raghavan

The thermodynamics of binding of unfolded polypeptides to the chaperone SecB was investigated in vitro by isothermal titration calorimetry and fluorescence spectroscopy. The substrates were reduced...

Protein stabilization through phage display (2000)

Chakravarty, Suvobrata, Mitra, Nivedita, Queitsch, Iris, Surolia, Avadhesha, Varadarajan, Raghavan, Dubel, Stefan

RNase S consists of two proteolytic fragments of RNase A, residues 1–20 (S20) and residues 21–124 (S pro). A 15-mer peptide (S15p) with high affinity for S pro was selected from a phage display...

Elucidation of determinants of protein stability through genome sequence analysis (2000)

Chakravarty, Suvobrata, Varadarajan, Raghavan

Sequences of putative soluble proteins from complete genomes of eight thermophiles and 12 mesophiles were analyzed to gain insight into determinants of protein thermostability. The predator algorithm...

Unfolding Thermodynamics of the Tetrameric Chaperone, SecB (2000)

Panse, Vikram G, Swaminathan, Chittor P, Aloor, Jim J, Surolia, Avadhesha, Varadarajan, Raghavan

SecB is a cytosolic tetrameric chaperone in Escherichia coli, which maintains polypeptides, destined for export in a translocation competent state. The thermodynamics of unfolding of SecB was studied...

A Thermodynamic Coupling Mechanism for the Disaggregation of a Model Peptide Substrate by Chaperone SecB (2000)

Panse, Vikram G, Vogel, Pia, Trommer, Wolfgang E, Varadarajan, Raghavan

Molecular chaperones prevent protein aggregation in vivo and in vitro. In a few cases, multichaperone systems are capable of dissociating aggregated state(s) of substrate proteins, although little is...

Thermodynamic and kinetic analysis of the Escherichia coli thioredoxin-C fragment complementation system (1999)

Ghoshal, Alokesh K, Swaminathan, Chittoor P, Thomas, Celestine J, Surolia, Avadhesha, Varadarajan, Raghavan

Escherichia coli thioredoxin was cleaved with CNBr at its single Met residue at position 37, which lies in the middle of a long \alpha -helix. The two fragments, 1–37 and 38–108, were purified...

Residue depth: A novel parameter for the analysis of protein structure and stability (1999)

Chakravarty, Suvobrata, Varadarajan, Raghavan

Accessible surface area is a parameter that is widely used in analyses of protein structure and stability. Accessible surface area does not, however, distinguish between atoms just below the protein...

Prediction of the maximal stability temperature of monomeric globular proteins solely from amino acid sequence (1999)

Ganesh, C, Eswar, Narayanan, Srivastava, Sarika, Ramakrishnan, Chandrasekharan, Varadarajan, Raghavan

Globular protein thermostability is characterized the cold denaturation, maximal stability $(T_{ms})$ and heat denaturation temperatures. For mesophilic globular proteins, $T_{ms}$ typically ranges...

Disordered N-terminal residues affect the folding thermodynamics and kinetics of maltose binding protein (1999)

Ganesh, C, Banerjee, Antara, Shah, Aseema, Varadarajan, Raghavan

Maltose binding protein (MBP) exhibits a slow phase of folding at pH 7.4, 298 K. The kinetics of this phase has been characterized as a function of denaturant concentration and temperature....

Design of temperature-sensitive mutants solely from amino acid sequence

Chakshusmathi, Ghadiyaram, Mondal, Kajari, Lakshmi, G. Santosh, Singh, Guramrit, Roy, Ankita, Ch., Ravindra Babu, ...

Temperature-sensitive (Ts) mutants are a powerful tool with which to study gene function in vivo. Ts mutants are typically generated by random mutagenesis followed by laborious screening procedures....

Characterization of gp120 and Its Single-Chain Derivatives, gp120-CD4D12 and gp120-M9: Implications for Targeting the CD4i Epitope in Human Immunodeficiency Virus Vaccine Design

Varadarajan, Raghavan, Sharma, Deepak, Chakraborty, Kausik, Patel, Mayuri, Citron, Michael, Sinha, Prem, ...

Single-chain derivatives of JRFL gp120 linked to the first two domains of human CD4 (gp120-CD4D12) or to the CD4 miniprotein analog CD4M9 (gp120-M9), have been constructed. Biacore studies revealed...

NMR structural analysis of a peptide mimic of the bridging sheet of HIV-1 gp120 in methanol and water

Chakraborty, Kausik, Shivakumar, P., Raghothama, S., Varadarajan, Raghavan

gp120 is a subunit of the Env (viral envelope protein) of HIV-1. The protein consists of inner and outer domains linked by a bridging sheet. Several gp120 residues that bind the neutralizing antibody...

Thermodynamic characterization of monomeric and dimeric forms of CcdB (controller of cell division or death B protein).

Bajaj, Kanika, Chakshusmathi, Ghadiyaram, Bachhawat-Sikder, Kiran, Surolia, Avadhesha, Varadarajan, Raghavan

The protein CcdB (controller of cell division or death B) is an F-plasmid-encoded toxin that acts as an inhibitor of Escherichia coli DNA gyrase. The stability and aggregation state of CcdB have been...

Mutagenesis-based definitions and probes of residue burial in proteins

Bajaj, Kanika, Chakrabarti, Purbani, Varadarajan, Raghavan

Every residue of the 101-aa Escherichia coli toxin CcdB was substituted with Ala, Asp, Glu, Lys, and Arg by using site-directed mutagenesis. The activity of each mutant in vivo was characterized as a...

Design of temperature-sensitive mutants solely from amino acid sequence

Chakshusmathi, Ghadiyaram, Mondal, Kajari, Lakshmi, G. Santosh, Singh, Guramrit, Roy, Ankita, Ch., Ravindra Babu, ...

Temperature-sensitive (Ts) mutants are a powerful tool with which to study gene function in vivo. Ts mutants are typically generated by random mutagenesis followed by laborious screening procedures....

Characterization of gp120 and Its Single-Chain Derivatives, gp120-CD4D12 and gp120-M9: Implications for Targeting the CD4i Epitope in Human Immunodeficiency Virus Vaccine Design

Varadarajan, Raghavan, Sharma, Deepak, Chakraborty, Kausik, Patel, Mayuri, Citron, Michael, Sinha, Prem, ...

Single-chain derivatives of JRFL gp120 linked to the first two domains of human CD4 (gp120-CD4D12) or to the CD4 miniprotein analog CD4M9 (gp120-M9), have been constructed. Biacore studies revealed...

NMR structural analysis of a peptide mimic of the bridging sheet of HIV-1 gp120 in methanol and water

Chakraborty, Kausik, Shivakumar, P., Raghothama, S., Varadarajan, Raghavan

gp120 is a subunit of the Env (viral envelope protein) of HIV-1. The protein consists of inner and outer domains linked by a bridging sheet. Several gp120 residues that bind the neutralizing antibody...

Thermodynamic characterization of monomeric and dimeric forms of CcdB (controller of cell division or death B protein).

Bajaj, Kanika, Chakshusmathi, Ghadiyaram, Bachhawat-Sikder, Kiran, Surolia, Avadhesha, Varadarajan, Raghavan

The protein CcdB (controller of cell division or death B) is an F-plasmid-encoded toxin that acts as an inhibitor of Escherichia coli DNA gyrase. The stability and aggregation state of CcdB have been...

Mutagenesis-based definitions and probes of residue burial in proteins

Bajaj, Kanika, Chakrabarti, Purbani, Varadarajan, Raghavan

Every residue of the 101-aa Escherichia coli toxin CcdB was substituted with Ala, Asp, Glu, Lys, and Arg by using site-directed mutagenesis. The activity of each mutant in vivo was characterized as a...

Design of immunogens that present the crown of the HIV-1 V3 loop in a conformation competent to generate 447-52D-like antibodies

Chakraborty, Kausik, Durani, Venuka, Miranda, Edward Roshan, Citron, Michael, Liang, Xiaoping, Schleif, William, ...

gp120 is a subunit of the envelope glycoprotein of HIV-1. The third variable loop region of gp120 (V3 loop) contains multiple immunodominant epitopes and is also functionally important for deciding...

Stereochemical Criteria for Prediction of the Effects of Proline Mutations on Protein Stability

Bajaj, Kanika, Madhusudhan, M. S, Adkar, Bharat V, Chakrabarti, Purbani, Ramakrishnan, C, Sali, Andrej, ...

When incorporated into a polypeptide chain, proline (Pro) differs from all other naturally occurring amino acid residues in two important respects. The φ dihedral angle of Pro is constrained to...

Reversible formation of on-pathway macroscopic aggregates during the folding of maltose binding protein

Ganesh, C., Zaidi, Faisal. N., Udgaonkar, Jayant. B., Varadarajan, Raghavan

Maltose binding protein (MBP) is widely used as a model for protein folding and export studies. We show here that macroscopic aggregates form transiently during the refolding of MBP at micromolar...