Mohammad Javed Equbal | Children's Hospital of Philadelphia (original) (raw)

Papers by Mohammad Javed Equbal

Research paper thumbnail of Immunodominant protein MIP_05962 from Mycobacterium indicus pranii displays chaperone activity

The FEBS Journal, 2017

Tuberculosis, a contagious disease of infectious origin is currently a major cause of deaths worl... more Tuberculosis, a contagious disease of infectious origin is currently a major cause of deaths worldwide. Mycobacterium indicus pranii (MIP), a saprophytic nonpathogen and a potent immunomodulator is currently being investigated as an intervention against tuberculosis along with many other diseases with positive outcome. The apparent paradox of multiple chaperones in mycobacterial species and enigma about the cellular functions of the client proteins of these chaperones need to be explored. Chaperones are the known immunomodulators; thus, there is need to exploit the proteome of MIP for identification and characterization of putative chaperones. One of the immunogenic proteins, MIP_05962 is a member of heat shock protein (HSP) 20 family due to the presence of a-crystallin domain, and has amino acid similarity with Mycobacterium leprae HSP18 protein. The diverse functions of M. leprae HSP18 in stress conditions implicate MIP_05962 as an important protein that needs to be explored. Biophysical and biochemical characterization of the said protein proved it to be a chaperone. The observations of aggregation prevention and refolding of substrate proteins in the presence of MIP_05962 along with interaction with non-native proteins, surface hydrophobicity, formation of large oligomers, in-vivo thermal rescue of Escherichia coli expressing MIP_05962, enhancing solubility of insoluble protein maltodextrin glucosidase (MalZ) under in-vivo conditions, and thermal stability and reversibility confirmed MIP_05962 as a molecular chaperone.

Research paper thumbnail of Novel expression system for Corynebacterium acetoacidophilum and Escherichia coli based on the T7 RNA polymerase-dependent promoter

Applied Microbiology and Biotechnology, 2013

The industrially important species of corynebacteria viz. Corynebacterium acetoacidophilum appear... more The industrially important species of corynebacteria viz. Corynebacterium acetoacidophilum appear to be alternative hosts for recombinant protein production; despite many efforts, a strong promoter-based system in corynebacteria has not been established so far. Described here is a T7 promoter-based expression system which was functional in both gram-positive C. acetoacidophilum and gram-negative Escherichia coli in an external inducer independent manner. This is the very first report of a T7 expression system for Corynebacterium sp. Also, it is a useful addition in the existing T7 expression systems of E. coli.

Research paper thumbnail of Inhibition of PKCβ Mediates Cardioprotective Activity of Ambrex against Isoproterenol-Induced Myocardial Necrosis: in vivo and in silico Studies

Biology and Medicine, 2018

Aims and objectives: The current study characterized the morphology of Ambrex formulation by Scan... more Aims and objectives: The current study characterized the morphology of Ambrex formulation by Scanning Electron Microscopy and assessed its cardioprotective activity against Isoproterenol (ISPH)-induced myocardial necrosis in rats by biochemical and histopathological evaluations, and also attempted to predict the prospective protein-targets of Ambrex and the signaling pathway that mediates this activity through molecular docking approach. Materials and methods: Sprague-Dawley male rats (4 groups, 6 rats per group) chosen for the current study were acclimatized to the laboratory conditions for 7 days prior to actual treatment; they were pretreated with Ambrex (40 mg/kg b.wt/day, p.o) everday for 21 days and then intoxicated with ISPH (85 mg/kg b.wt, s.c) on day-20 and 21 to experimentally induce myocardial necrosis. The extent of ISPH-induced myocardial necrosis was quantified in terms of the serum levels of two cardiac biomarkers: creatine kinase-MB and lactate dehydrogenase. The extent of ISPH-induced oxidative stress was quantified in terms of the tissue levels of five oxidative stress biomarkers: superoxide dismutase, catalase, reduced glutathione, glutathione peroxidase and lipid peroxidation. Results and discussion: The Scanning Electron Microscopy image of Ambrex formulation showed the formation of nanoparticles with thickness of 65 nm, making Ambrex a unique metal-deficient Siddha-medicine based polyherbal nano-formulation characterized and evaluated in India. Pretreatment with Ambrex attenuated the extent of ISPH-induced oxidative stress, lipid peroxidation and generation of reactive oxygen species as reflected by biochemical evaluations, and also ameliorated the degree of ISPH-induced myocardial necrosis and membrane damage as reflected by histopathological evaluations. The results of molecular docking revealed that Withaferin-A and Methyl Commate-A (the key metabolites of Withania somnifera and Ambrex respectively) inhibit Protein Kinase-C Beta, and renders Ambrex its cardioprotective activity by maintaining the intracellular antioxidant homeostasis and myocardial membrane architecture.

Research paper thumbnail of Role of N-terminal region of Escherichia coli maltodextrin glucosidase in folding and function of the protein

Biochimica et biophysica acta, Sep 16, 2016

Maltodextrin glucosidase (MalZ) hydrolyses short malto-oligosaccharides from the reducing end rel... more Maltodextrin glucosidase (MalZ) hydrolyses short malto-oligosaccharides from the reducing end releasing glucose and maltose in Escherichia coli. MalZ is a highly aggregation prone protein and molecular chaperonins GroEL and GroES assist in the folding of this protein to a substantial level. The N-terminal region of this enzyme appears to be a unique domain as seen in sequence comparison studies with other amylases as well as through homology modelling. The sequence and homology model analysis show a probability of disorder in the N-Terminal region of MalZ. The crystal structure of this enzyme has been reported in the present communication. Based on the crystallographic structure, it has been interpreted that the N-terminal region of the enzyme (Met1-Phe131) might be unstructured or flexible. To understand the role of the N-terminal region of MalZ in its enzymatic activity, and overall stability, a truncated version (Ala111-His616) of MalZ was created. The truncated version failed to...

Research paper thumbnail of Prospective therapeutic potential of Tanshinone IIA: An updated overview

Research paper thumbnail of Recent Nano-based therapeutic intervention of Bioactive Sesquiterpenes: Prospects in cancer therapeutics

Current Pharmaceutical Design

: In recent scenario, nanotechnology based therapeutics intervention has gained tremendous impetu... more : In recent scenario, nanotechnology based therapeutics intervention has gained tremendous impetus all across the globe. Nano-based pharmacological intervention of various bioactive compounds has been explored on an increasing scale. Sesquiterpenes are major constituents of essential oils (EOs) present in various plant species which embodies intriguing therapeutic potentials. However, owing to their poor physico-chemical properties; they have pharmacological limitations. Recent advances in nano-based therapeutic interventions offer various avenues to improve their therapeutic applicability. Reckoning with these, the present review collates various nano-based therapeutic intervention of sesquiterpenes with prospective potential against various debilitating diseases especially cancer. In our viewpoint, considering the burgeoning advancement in the field of nanomedicine; in the near future, clinical applicability of these nano-formulated sesquiterpenes can be foreseen with great enthusiasm.

Research paper thumbnail of Recent Nano based Therapeutic Intervention of Bioactive Sesquiterpenes Prospects in Cancer Therapeutics

Current Pharmaceutical Design, 2020

In the recent scenario, nanotechnology-based therapeutics intervention has gained tremendous impe... more In the recent scenario, nanotechnology-based therapeutics intervention has gained tremendous impetus
all across the globe. Nano-based pharmacological intervention of various bioactive compounds has been explored
on an increasing scale. Sesquiterpenes are major constituents of essential oils (EOs) present in various plant species
which possess intriguing therapeutic potentials. However, owing to their poor physicochemical properties;
they have pharmacological limitations. Recent advances in nano-based therapeutic interventions offer various
avenues to improve their therapeutic applicability. Reckoning with these, the present review collates various
nano-based therapeutic intervention of sesquiterpenes with prospective potential against various debilitating diseases
especially cancer. In our viewpoint, considering the burgeoning advancement in the field of nanomedicine;
in the near future, the clinical applicability of these nano-formulated sesquiterpenes can be foreseen with great
enthusiasm.

Research paper thumbnail of Inhibition of PKCβ Mediates Cardioprotective Activity of Ambrex against Isoproterenol-Induced Myocardial Necrosis: in vivo and in silico Studies

Biology and Medicine, 2018

Aims and objectives: The current study characterized the morphology of Ambrex formulation by Scan... more Aims and objectives: The current study characterized the morphology of Ambrex formulation by Scanning Electron Microscopy and assessed its cardioprotective activity against Isoproterenol (ISPH)-induced myocardial necrosis in rats by biochemical and histopathological evaluations, and also attempted to predict the prospective protein-targets of Ambrex and the signaling pathway that mediates this activity through molecular docking approach. Materials and methods: Sprague-Dawley male rats (4 groups, 6 rats per group) chosen for the current study were acclimatized to the laboratory conditions for 7 days prior to actual treatment; they were pretreated with Ambrex (40 mg/kg b.wt/day, p.o) everday for 21 days and then intoxicated with ISPH (85 mg/kg b.wt, s.c) on day-20 and 21 to experimentally induce myocardial necrosis. The extent of ISPH-induced myocardial necrosis was quantified in terms of the serum levels of two cardiac biomarkers: creatine kinase-MB and lactate dehydrogenase. The extent of ISPH-induced oxidative stress was quantified in terms of the tissue levels of five oxidative stress biomarkers: superoxide dismutase, catalase, reduced glutathione, glutathione peroxidase and lipid peroxidation. Results and discussion: The Scanning Electron Microscopy image of Ambrex formulation showed the formation of nanoparticles with thickness of 65 nm, making Ambrex a unique metal-deficient Siddha-medicine based polyherbal nano-formulation characterized and evaluated in India. Pretreatment with Ambrex attenuated the extent of ISPH-induced oxidative stress, lipid peroxidation and generation of reactive oxygen species as reflected by biochemical evaluations, and also ameliorated the degree of ISPH-induced myocardial necrosis and membrane damage as reflected by histopathological evaluations. The results of molecular docking revealed that Withaferin-A and Methyl Commate-A (the key metabolites of Withania somnifera and Ambrex respectively) inhibit Protein Kinase-C Beta, and renders Ambrex its cardioprotective activity by maintaining the intracellular antioxidant homeostasis and myocardial membrane architecture.

Research paper thumbnail of Immunodominant protein MIP_05962 from Mycobacterium indicus pranii displays chaperone activity

FEBS Journal, 2017

Tuberculosis, a contagious disease of infectious origin is currently a major cause of deaths worl... more Tuberculosis, a contagious disease of infectious origin is currently a major
cause of deaths worldwide. Mycobacterium indicus pranii (MIP), a saprophytic
nonpathogen and a potent immunomodulator is currently being investigated
as an intervention against tuberculosis along with many other diseases
with positive outcome. The apparent paradox of multiple chaperones in
mycobacterial species and enigma about the cellular functions of the client
proteins of these chaperones need to be explored. Chaperones are the known
immunomodulators; thus, there is need to exploit the proteome of MIP for
identification and characterization of putative chaperones. One of the
immunogenic proteins, MIP_05962 is a member of heat shock protein (HSP)
20 family due to the presence of a-crystallin domain, and has amino acid similarity
with Mycobacterium leprae HSP18 protein. The diverse functions of
M. leprae HSP18 in stress conditions implicate MIP_05962 as an important
protein that needs to be explored. Biophysical and biochemical characterization
of the said protein proved it to be a chaperone. The observations of aggregation
prevention and refolding of substrate proteins in the presence of
MIP_05962 along with interaction with non-native proteins, surface
hydrophobicity, formation of large oligomers, in-vivo thermal rescue of
Escherichia coli expressing MIP_05962, enhancing solubility of insoluble protein
maltodextrin glucosidase (MalZ) under in-vivo conditions, and thermal
stability and reversibility confirmed MIP_05962 as a molecular chaperone.

Research paper thumbnail of Role of N-terminal region of Escherichia coli maltodextrin glucosidase in folding and function of the protein

BBA - Proteins and Proteomics , 2016

Maltodextrin glucosidase (MalZ) hydrolyses short malto-oligosaccharides from the reducing end rel... more Maltodextrin glucosidase (MalZ) hydrolyses short malto-oligosaccharides from the reducing end releasing glucose and maltose in Escherichia coli. MalZ is a highly aggregation prone protein and molecular chaperonins GroEL and GroES assist in the folding of this protein to a substantial level. The N-terminal region of this enzyme appears to be a unique domain as seen in sequence comparison studies with other amylases as well as through homology modelling. The sequence and homology model analysis show a probability of disorder in the N-Terminal region of MalZ. The crystal structure of this enzyme has been reported in the present communication. Based on the crystallographic structure, it has been interpreted that the N-terminal region of the enzyme (Met1– Phe131) might be unstructured or flexible. To understand the role of the N-terminal region of MalZ in its enzymatic activity, and overall stability, a truncated version (Ala111-His616) of MalZ was created. The truncated version failed to fold into an active enzyme both in E. coli cytosol and in vitro even with the assistance of chaperonins GroEL and GroES. Furthermore, the refolding effort of N-truncated MalZ in the presence of isolated N-terminal domain didn't succeed. Our studies suggest that while the structural rigidity or orientation of the N-terminal region of the MalZ protein may not be essential for its stability and function, but the said domain is likely to play an important role in the formation of the native structure of the protein when present as an integral part of the protein.

Research paper thumbnail of Nanotechnology as a next generation therapeutics: Hope for cancer treatment

Nanoparticle-based carriers are one of the promising approaches for diagnosis and treatment of ca... more Nanoparticle-based carriers are one of the promising approaches for diagnosis and treatment of cancer which may bring hope in cancer patients in near future because of their unique physical, chemical and biological properties which allow them to bind, adsorb, and carry both hydrophobic and hydrophilic drugs, molecules, and imaging agents with higher efficiency. Several biodegradable and biocompatible nanoparticles have been developed for cancer therapy such as liposomes, polymer-based nanoparticles, polymersomes, micelles, proteins, dendrimers, and inorganic nanoparticles. In this chapter, we will discuss the synthesis and properties of nanoparticles, and different types of nanoparticle technologies developed for cancer therapy. We will also highlight the photodynamic therapy, photothermal therapy, and theranostic agents manufactured for cancer therapy and diagnosis. This chapter also examines nanotherapeutics which is approved and is in clinical and preclinical stages. Moreover, we...

Research paper thumbnail of Novel expression system for Corynebacterium acetoacidophilum and Escherichia coli based on the T7 RNA polymerase-dependent promoter

Appl Microbiol Biotechnol , 2013

The industrially important species of corynebacteria viz. Corynebacterium acetoacidophilum appear... more The industrially important species of corynebacteria viz. Corynebacterium acetoacidophilum appear to be alternative hosts for recombinant protein production; despite many efforts, a strong promoter-based system in corynebacteria has not been established so far. Described here is a T7 promoter-based expression system which was functional in both gram-positive C. acetoacidophilum and gram-negative Escherichia coli in an external inducer independent manner. This is the very first report of a T7 expression system for Corynebacterium sp. Also, it is a useful addition in the existing T7 expression systems of E. coli.

Research paper thumbnail of Immunodominant protein MIP_05962 from Mycobacterium indicus pranii displays chaperone activity

The FEBS Journal, 2017

Tuberculosis, a contagious disease of infectious origin is currently a major cause of deaths worl... more Tuberculosis, a contagious disease of infectious origin is currently a major cause of deaths worldwide. Mycobacterium indicus pranii (MIP), a saprophytic nonpathogen and a potent immunomodulator is currently being investigated as an intervention against tuberculosis along with many other diseases with positive outcome. The apparent paradox of multiple chaperones in mycobacterial species and enigma about the cellular functions of the client proteins of these chaperones need to be explored. Chaperones are the known immunomodulators; thus, there is need to exploit the proteome of MIP for identification and characterization of putative chaperones. One of the immunogenic proteins, MIP_05962 is a member of heat shock protein (HSP) 20 family due to the presence of a-crystallin domain, and has amino acid similarity with Mycobacterium leprae HSP18 protein. The diverse functions of M. leprae HSP18 in stress conditions implicate MIP_05962 as an important protein that needs to be explored. Biophysical and biochemical characterization of the said protein proved it to be a chaperone. The observations of aggregation prevention and refolding of substrate proteins in the presence of MIP_05962 along with interaction with non-native proteins, surface hydrophobicity, formation of large oligomers, in-vivo thermal rescue of Escherichia coli expressing MIP_05962, enhancing solubility of insoluble protein maltodextrin glucosidase (MalZ) under in-vivo conditions, and thermal stability and reversibility confirmed MIP_05962 as a molecular chaperone.

Research paper thumbnail of Novel expression system for Corynebacterium acetoacidophilum and Escherichia coli based on the T7 RNA polymerase-dependent promoter

Applied Microbiology and Biotechnology, 2013

The industrially important species of corynebacteria viz. Corynebacterium acetoacidophilum appear... more The industrially important species of corynebacteria viz. Corynebacterium acetoacidophilum appear to be alternative hosts for recombinant protein production; despite many efforts, a strong promoter-based system in corynebacteria has not been established so far. Described here is a T7 promoter-based expression system which was functional in both gram-positive C. acetoacidophilum and gram-negative Escherichia coli in an external inducer independent manner. This is the very first report of a T7 expression system for Corynebacterium sp. Also, it is a useful addition in the existing T7 expression systems of E. coli.

Research paper thumbnail of Inhibition of PKCβ Mediates Cardioprotective Activity of Ambrex against Isoproterenol-Induced Myocardial Necrosis: in vivo and in silico Studies

Biology and Medicine, 2018

Aims and objectives: The current study characterized the morphology of Ambrex formulation by Scan... more Aims and objectives: The current study characterized the morphology of Ambrex formulation by Scanning Electron Microscopy and assessed its cardioprotective activity against Isoproterenol (ISPH)-induced myocardial necrosis in rats by biochemical and histopathological evaluations, and also attempted to predict the prospective protein-targets of Ambrex and the signaling pathway that mediates this activity through molecular docking approach. Materials and methods: Sprague-Dawley male rats (4 groups, 6 rats per group) chosen for the current study were acclimatized to the laboratory conditions for 7 days prior to actual treatment; they were pretreated with Ambrex (40 mg/kg b.wt/day, p.o) everday for 21 days and then intoxicated with ISPH (85 mg/kg b.wt, s.c) on day-20 and 21 to experimentally induce myocardial necrosis. The extent of ISPH-induced myocardial necrosis was quantified in terms of the serum levels of two cardiac biomarkers: creatine kinase-MB and lactate dehydrogenase. The extent of ISPH-induced oxidative stress was quantified in terms of the tissue levels of five oxidative stress biomarkers: superoxide dismutase, catalase, reduced glutathione, glutathione peroxidase and lipid peroxidation. Results and discussion: The Scanning Electron Microscopy image of Ambrex formulation showed the formation of nanoparticles with thickness of 65 nm, making Ambrex a unique metal-deficient Siddha-medicine based polyherbal nano-formulation characterized and evaluated in India. Pretreatment with Ambrex attenuated the extent of ISPH-induced oxidative stress, lipid peroxidation and generation of reactive oxygen species as reflected by biochemical evaluations, and also ameliorated the degree of ISPH-induced myocardial necrosis and membrane damage as reflected by histopathological evaluations. The results of molecular docking revealed that Withaferin-A and Methyl Commate-A (the key metabolites of Withania somnifera and Ambrex respectively) inhibit Protein Kinase-C Beta, and renders Ambrex its cardioprotective activity by maintaining the intracellular antioxidant homeostasis and myocardial membrane architecture.

Research paper thumbnail of Role of N-terminal region of Escherichia coli maltodextrin glucosidase in folding and function of the protein

Biochimica et biophysica acta, Sep 16, 2016

Maltodextrin glucosidase (MalZ) hydrolyses short malto-oligosaccharides from the reducing end rel... more Maltodextrin glucosidase (MalZ) hydrolyses short malto-oligosaccharides from the reducing end releasing glucose and maltose in Escherichia coli. MalZ is a highly aggregation prone protein and molecular chaperonins GroEL and GroES assist in the folding of this protein to a substantial level. The N-terminal region of this enzyme appears to be a unique domain as seen in sequence comparison studies with other amylases as well as through homology modelling. The sequence and homology model analysis show a probability of disorder in the N-Terminal region of MalZ. The crystal structure of this enzyme has been reported in the present communication. Based on the crystallographic structure, it has been interpreted that the N-terminal region of the enzyme (Met1-Phe131) might be unstructured or flexible. To understand the role of the N-terminal region of MalZ in its enzymatic activity, and overall stability, a truncated version (Ala111-His616) of MalZ was created. The truncated version failed to...

Research paper thumbnail of Prospective therapeutic potential of Tanshinone IIA: An updated overview

Research paper thumbnail of Recent Nano-based therapeutic intervention of Bioactive Sesquiterpenes: Prospects in cancer therapeutics

Current Pharmaceutical Design

: In recent scenario, nanotechnology based therapeutics intervention has gained tremendous impetu... more : In recent scenario, nanotechnology based therapeutics intervention has gained tremendous impetus all across the globe. Nano-based pharmacological intervention of various bioactive compounds has been explored on an increasing scale. Sesquiterpenes are major constituents of essential oils (EOs) present in various plant species which embodies intriguing therapeutic potentials. However, owing to their poor physico-chemical properties; they have pharmacological limitations. Recent advances in nano-based therapeutic interventions offer various avenues to improve their therapeutic applicability. Reckoning with these, the present review collates various nano-based therapeutic intervention of sesquiterpenes with prospective potential against various debilitating diseases especially cancer. In our viewpoint, considering the burgeoning advancement in the field of nanomedicine; in the near future, clinical applicability of these nano-formulated sesquiterpenes can be foreseen with great enthusiasm.

Research paper thumbnail of Recent Nano based Therapeutic Intervention of Bioactive Sesquiterpenes Prospects in Cancer Therapeutics

Current Pharmaceutical Design, 2020

In the recent scenario, nanotechnology-based therapeutics intervention has gained tremendous impe... more In the recent scenario, nanotechnology-based therapeutics intervention has gained tremendous impetus
all across the globe. Nano-based pharmacological intervention of various bioactive compounds has been explored
on an increasing scale. Sesquiterpenes are major constituents of essential oils (EOs) present in various plant species
which possess intriguing therapeutic potentials. However, owing to their poor physicochemical properties;
they have pharmacological limitations. Recent advances in nano-based therapeutic interventions offer various
avenues to improve their therapeutic applicability. Reckoning with these, the present review collates various
nano-based therapeutic intervention of sesquiterpenes with prospective potential against various debilitating diseases
especially cancer. In our viewpoint, considering the burgeoning advancement in the field of nanomedicine;
in the near future, the clinical applicability of these nano-formulated sesquiterpenes can be foreseen with great
enthusiasm.

Research paper thumbnail of Inhibition of PKCβ Mediates Cardioprotective Activity of Ambrex against Isoproterenol-Induced Myocardial Necrosis: in vivo and in silico Studies

Biology and Medicine, 2018

Aims and objectives: The current study characterized the morphology of Ambrex formulation by Scan... more Aims and objectives: The current study characterized the morphology of Ambrex formulation by Scanning Electron Microscopy and assessed its cardioprotective activity against Isoproterenol (ISPH)-induced myocardial necrosis in rats by biochemical and histopathological evaluations, and also attempted to predict the prospective protein-targets of Ambrex and the signaling pathway that mediates this activity through molecular docking approach. Materials and methods: Sprague-Dawley male rats (4 groups, 6 rats per group) chosen for the current study were acclimatized to the laboratory conditions for 7 days prior to actual treatment; they were pretreated with Ambrex (40 mg/kg b.wt/day, p.o) everday for 21 days and then intoxicated with ISPH (85 mg/kg b.wt, s.c) on day-20 and 21 to experimentally induce myocardial necrosis. The extent of ISPH-induced myocardial necrosis was quantified in terms of the serum levels of two cardiac biomarkers: creatine kinase-MB and lactate dehydrogenase. The extent of ISPH-induced oxidative stress was quantified in terms of the tissue levels of five oxidative stress biomarkers: superoxide dismutase, catalase, reduced glutathione, glutathione peroxidase and lipid peroxidation. Results and discussion: The Scanning Electron Microscopy image of Ambrex formulation showed the formation of nanoparticles with thickness of 65 nm, making Ambrex a unique metal-deficient Siddha-medicine based polyherbal nano-formulation characterized and evaluated in India. Pretreatment with Ambrex attenuated the extent of ISPH-induced oxidative stress, lipid peroxidation and generation of reactive oxygen species as reflected by biochemical evaluations, and also ameliorated the degree of ISPH-induced myocardial necrosis and membrane damage as reflected by histopathological evaluations. The results of molecular docking revealed that Withaferin-A and Methyl Commate-A (the key metabolites of Withania somnifera and Ambrex respectively) inhibit Protein Kinase-C Beta, and renders Ambrex its cardioprotective activity by maintaining the intracellular antioxidant homeostasis and myocardial membrane architecture.

Research paper thumbnail of Immunodominant protein MIP_05962 from Mycobacterium indicus pranii displays chaperone activity

FEBS Journal, 2017

Tuberculosis, a contagious disease of infectious origin is currently a major cause of deaths worl... more Tuberculosis, a contagious disease of infectious origin is currently a major
cause of deaths worldwide. Mycobacterium indicus pranii (MIP), a saprophytic
nonpathogen and a potent immunomodulator is currently being investigated
as an intervention against tuberculosis along with many other diseases
with positive outcome. The apparent paradox of multiple chaperones in
mycobacterial species and enigma about the cellular functions of the client
proteins of these chaperones need to be explored. Chaperones are the known
immunomodulators; thus, there is need to exploit the proteome of MIP for
identification and characterization of putative chaperones. One of the
immunogenic proteins, MIP_05962 is a member of heat shock protein (HSP)
20 family due to the presence of a-crystallin domain, and has amino acid similarity
with Mycobacterium leprae HSP18 protein. The diverse functions of
M. leprae HSP18 in stress conditions implicate MIP_05962 as an important
protein that needs to be explored. Biophysical and biochemical characterization
of the said protein proved it to be a chaperone. The observations of aggregation
prevention and refolding of substrate proteins in the presence of
MIP_05962 along with interaction with non-native proteins, surface
hydrophobicity, formation of large oligomers, in-vivo thermal rescue of
Escherichia coli expressing MIP_05962, enhancing solubility of insoluble protein
maltodextrin glucosidase (MalZ) under in-vivo conditions, and thermal
stability and reversibility confirmed MIP_05962 as a molecular chaperone.

Research paper thumbnail of Role of N-terminal region of Escherichia coli maltodextrin glucosidase in folding and function of the protein

BBA - Proteins and Proteomics , 2016

Maltodextrin glucosidase (MalZ) hydrolyses short malto-oligosaccharides from the reducing end rel... more Maltodextrin glucosidase (MalZ) hydrolyses short malto-oligosaccharides from the reducing end releasing glucose and maltose in Escherichia coli. MalZ is a highly aggregation prone protein and molecular chaperonins GroEL and GroES assist in the folding of this protein to a substantial level. The N-terminal region of this enzyme appears to be a unique domain as seen in sequence comparison studies with other amylases as well as through homology modelling. The sequence and homology model analysis show a probability of disorder in the N-Terminal region of MalZ. The crystal structure of this enzyme has been reported in the present communication. Based on the crystallographic structure, it has been interpreted that the N-terminal region of the enzyme (Met1– Phe131) might be unstructured or flexible. To understand the role of the N-terminal region of MalZ in its enzymatic activity, and overall stability, a truncated version (Ala111-His616) of MalZ was created. The truncated version failed to fold into an active enzyme both in E. coli cytosol and in vitro even with the assistance of chaperonins GroEL and GroES. Furthermore, the refolding effort of N-truncated MalZ in the presence of isolated N-terminal domain didn't succeed. Our studies suggest that while the structural rigidity or orientation of the N-terminal region of the MalZ protein may not be essential for its stability and function, but the said domain is likely to play an important role in the formation of the native structure of the protein when present as an integral part of the protein.

Research paper thumbnail of Nanotechnology as a next generation therapeutics: Hope for cancer treatment

Nanoparticle-based carriers are one of the promising approaches for diagnosis and treatment of ca... more Nanoparticle-based carriers are one of the promising approaches for diagnosis and treatment of cancer which may bring hope in cancer patients in near future because of their unique physical, chemical and biological properties which allow them to bind, adsorb, and carry both hydrophobic and hydrophilic drugs, molecules, and imaging agents with higher efficiency. Several biodegradable and biocompatible nanoparticles have been developed for cancer therapy such as liposomes, polymer-based nanoparticles, polymersomes, micelles, proteins, dendrimers, and inorganic nanoparticles. In this chapter, we will discuss the synthesis and properties of nanoparticles, and different types of nanoparticle technologies developed for cancer therapy. We will also highlight the photodynamic therapy, photothermal therapy, and theranostic agents manufactured for cancer therapy and diagnosis. This chapter also examines nanotherapeutics which is approved and is in clinical and preclinical stages. Moreover, we...

Research paper thumbnail of Novel expression system for Corynebacterium acetoacidophilum and Escherichia coli based on the T7 RNA polymerase-dependent promoter

Appl Microbiol Biotechnol , 2013

The industrially important species of corynebacteria viz. Corynebacterium acetoacidophilum appear... more The industrially important species of corynebacteria viz. Corynebacterium acetoacidophilum appear to be alternative hosts for recombinant protein production; despite many efforts, a strong promoter-based system in corynebacteria has not been established so far. Described here is a T7 promoter-based expression system which was functional in both gram-positive C. acetoacidophilum and gram-negative Escherichia coli in an external inducer independent manner. This is the very first report of a T7 expression system for Corynebacterium sp. Also, it is a useful addition in the existing T7 expression systems of E. coli.