Tej P Singh
Encyclopedia
Tej P. Singh is an eminent India
n biophysicist who has made original and novel contributions to the structural studies of proteins and has implemented a strong programme on rational structure based drug design.
and lactoferrin
from several species, ribosome
inactivating protein and its complex with a natural ligand from mistletoe
, bifunctional inhibitor proteins from plant seeds and various serine proteases and their inhibitors have been determined by his group.
The elaborate structural studies of proteins from several important systems as potential drug targets such as phospholipase
A2, cyclooxygenase
, lipoxygenase
, endothelin
receptor, endothelin converting enzyme, breast cancer
regression proteins and matrix metanosomal proteins as well as their complexes with natural and designed synthetic ligands have been carried out.
His laboratory has submitted more than 301 sets of proteins structure coordinates in the protein data bank
(PDB) which makes it the highest number in India. Initially, he had contributed significantly on the structure - function studies of a number of antipyretic
, analgesic
and anti-inflammatory agents and then on antibactrial sufonamides and their derivatives. He had developed the rules of peptide design with alpha, beta – dehydro - amino acids through extensive studies using syntheses, and X-ray and NMR structure determinations. These design rules are being exploited for making specific peptides to act as tight inhibitors of target enzymes and potent antagonists of target receptors for eventually leading to useful therapeutic agents.
As part of his protein structural studies, a large number of structures of lactoferrin
proteins from various species in iron-saturated and apo-forms as well as those of its proteolytically generated monoferric functional N- and C-lobes have been determined in his laboratory through which it was demonstrated that large scale conformational changes occur in the structures of lactoferrins upon iron-binding and iron-release, cations other than ferric ion also bind to the iron-binding cleft but with lower affinity, similarly anions other than carbonate/bicarbonate can also bind with reduced potency, and bilobal lactoferrin
can be converted into two functional N-terminal and C-terminal lobes with proteinase K. It was only his group in the whole world that successfully demonstrated the proteolytic production of N- and C-terminal molecular halves of lactoferrin and determined their three-dimensional structures. These studies have provided valuable insights into the structural basis of iron-binding and iron-release in lactoferrins and their roles as antibacterial agents and in other therapeutic applications.
While carrying out enzymatic cleavage of lactoferrin proteins, a novel antifungal
decapeptide was discovered whose excellent potency against bacterial infections has been established.
His group has carried out extensive structural studies of phospholipase
A2 enzymes and their complexes with various natural compounds, substrate analogues, non-steroidal anti-inflammatory agents and designed peptides. The new molecules have also been designed against cyclooxygenase and lypoxygenase. The enzymes phospholipase A2, cyclooxygenase and lypoxygenase are involved in the production of pro-inflammatory compounds collectively called as eicosanoids. He has already developed several highly potent inhibitors that are under consideration for further evaluation as anti-inflammatory agents. His group has been practicing the rational approach of structure-based drug design for developing therapeutic agents against various inflammatory disorders such as rheumatism and arthritis using PLA2, COX-2 and LOX enzymes as macromolecular targets.
In yet another area of current interest, his group has determined the crystal structures of several secretory glycoproteins isolated from dry secretions of various mammalian species including humans. This is a new class of proteins, first time detected whose functions and structures were unknown. These proteins are implicated as protective signaling factors in the large scale tissue remodeling processes. Their role in the breast cancers as protective factors for the breast cancer cells makes them important targets for structure - based drug design and offers opportunities for developing new therapeutic agents against breast cancer. He has been able to design several peptides that bind to these proteins with potencies ranging up to 10-7 M. The crystal structures of the complexes of these proteins with designed peptides have helped in identifying the site of binding in this protein. The structures of the complexes with various oligosachharides have provided information about the potencies of sugar binding. It also indicated the type and nature of sugars that will bind to this class of proteins specifically. Furthermore, several crystal structures of the ternary complexes of these proteins with peptides and sugars have helped in understanding the mode of binding of these proteins to cell surface receptors.
Recently he initiated a new programme on Clinical Proteomics
in which it is intended to characterize all the proteins that are expressed during various patho/physiological conditions. The newly identified proteins will either be useful as biomarkers or they may be associated with the progression of diseases making them important targets for drug design.
He has published more than 307 research papers in the leading journals.
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|Structure of Peptidoglycan Recognition Protein
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. He started his research career in 1971 as a graduate student at the Indian Institute of Science
, Bangalore
. He obtained his Ph. D degree in the mid 70's working on the crystal structure determinations and design of anti-inflammatory analgesics for new drug discovery.
, who later received the Nobel Prize
. After his return to India he worked as a reader at Sardar Patel University (1980–83) and an Additional Professor (1984–85) in the Department of Biophysics at the All India Institute of Medical Sciences, New Delhi. He was appointed Professor and Head of the Department in 1986, where he established a flourishing school of structural biology and new drug discovery.
Distinguished Biotechnology Research Professor (DBT), 2009
GN Ramachandran Gold Medal for excellence in Science and Technology (CSIR), 2006
Distinguished Biotechnologist (DBT), 2006
Vice President, Indian National Science Academy, 2007–2009
JC Bose Memorial Award, 2005
Alexander von Humboldt Fellow, 1977
Canadian Development Agency Award, 1999
Fellow of the Indian Academy of Sciences, 1994
Fellow of the National Academy of Sciences, 1998
Fellow of the Indian National Science Academy, 2000 -
Fellow of the Third World Academy of Sciences : F.T.W.A.S. 2003 -
Member of the Commission on Biological Macromolecules of the International Union of Crystallography (IUCr) (2005–2008)
Executive member of the International Union of Pure and Applied Biophysics (IUPAB) (2002–2005)
Member Secretary of the INSA National Committee for IUPAB (1988–91)
Member of the INSA National Committee for International Union of Pure and Applied Biophysics (IUPAB) (1985–88)
Member of the INSA National Committee for International Union of Crystallography (IUCr) (2000–2003)
Ex-officio member of the Joint National Committee of INSA for IUPAB and IUCr (2002–2005) , (2005–2008)
Member of a committee to select fellows for Indian National Science Academy (2001–2003)
Member of the Committee to select fellows for the Indian Academy of Sciences, 2005
Member of the Indian Biophysical Society since 1977
Member of the Society of Biological Chemists of India , 1982
Vice President of the Indian Biophysical society (1994–1996)
Member of the American Society for Biochemistry and Molecular Biology (ASBMB), since 2000
Member Technology Development Board on Pharmaceutical Industry (2002)
Member of the Senate of Indian Institute of Technology Delhi, (2001–2002)
Chairman of the DST Committee for the Fast Track Programme in life Sciences (2002–2004) , (2005–2007)
Member of the Apex Committee of the DBT for the programme support at I.I.Sc. Bangalore (1998–2001), (2002–2004) , (2005–2008)
Member of the Programme Advisory Committee of DST on Biochemistry, Biophysics, Molecular Biology including Microbiology (1996–1998) , (1999–2001)
Member of the DBT task force on Basic Biology / Modern Biology (1996–1998) , (1999–2001)
Member of the DBT task force on Infrastructure (2001–2003) , (2004–2006) , (2006–2008)
Member of the DBT task force on Bioinformatics (1994–1996)
Member of the Advisory Committee of Biotechnology Teaching Programme of the Biotechnology Centre, JNU (2002)
Member of the Executive Committee of the Bioinformatics Centre at Madurai Kamraj University (2002–2003)
Member of the Academic Committee of the Biotechnology Unit of AMU, Aligarh (2004–2006)
Member of the Research Area Panel of the National Institute of Immunology (1994–1996)
Member of the Special Committee of the School of Life Sciences, JNU (1988–1990) , (1991–1993)
Member of the Special Committee of the Centre for Biotechnology, JNU (1991–1993) , (1994–1996) , (1997–1999) , (2000–2002) , (2003–2005)
Member of the Special Committee of the Special Centre of Molecular Medicine, JNU (2001–2003) , (2004–2006)
Member of the Special Committee of the School of Environmental Sciences, JNU (2001–2003) , (2004–2006)
Member of the Academic Committee of the Nuclear Science Centre, New Delhi, (2002–2004), (2004–2006)
Member of the Academic Committee of Central Drug Research Institute, Lucknow, (2005–2006)
Member of the Academic Committee of the Institute of Microbial Technology, Chandigarh, (2005–2006)
Member of the Executive Council of the Centre of Bioinformatics, Institute of Microbial Technology, Chandigarh, 2005
Member of the Academic Council of the Central Unversityof Hyderabad, 2006–2007
Executive member of the Council of the International Union of Pure and Applied Biophysics (IUPAB) (2005–2008)
K.K.Foundation National Award for Science and Technology, 2001
Chairman of the Fast-Track Programme of DST in Life Sciences, 2001–2003
Member of the Technology Development Board on Pharmaceutical Industry, 2002–2003
Executive member of the Council of International Union of Pure and Applied Biophysics, 2002–2005
Max-Planck - Humbodt Award - 1999
Canadian Development Agency Award - 1991
Danish International Development Agency Award - 1978
First Rank in M.Sc. in the University of Allahabad - 1971
India
India , officially the Republic of India , is a country in South Asia. It is the seventh-largest country by geographical area, the second-most populous country with over 1.2 billion people, and the most populous democracy in the world...
n biophysicist who has made original and novel contributions to the structural studies of proteins and has implemented a strong programme on rational structure based drug design.
Work
The three-dimensional structures of various proteins including lactoperoxidaseLactoperoxidase
Lactoperoxidase is a peroxidase enzyme secreted from mammary, salivary, and other mucosal glands that functions as a natural antibacterial agent. Lactoperoxidase is a member of the heme peroxidase family of enzymes. In humans, lactoperoxidase is encoded by the LPO gene.Lactoperoxidase catalyzes...
and lactoferrin
Lactoferrin
Lactoferrin , also known as lactotransferrin , is a multifunctional protein of the transferrin family. Lactoferrin is a globular glycoprotein with a molecular mass of about 80 kDa that is widely represented in various secretory fluids, such as milk, saliva, tears, and nasal secretions...
from several species, ribosome
Ribosome
A ribosome is a component of cells that assembles the twenty specific amino acid molecules to form the particular protein molecule determined by the nucleotide sequence of an RNA molecule....
inactivating protein and its complex with a natural ligand from mistletoe
Mistletoe
Mistletoe is the common name for obligate hemi-parasitic plants in several families in the order Santalales. The plants in question grow attached to and within the branches of a tree or shrub.-Mistletoe in the genus Viscum:...
, bifunctional inhibitor proteins from plant seeds and various serine proteases and their inhibitors have been determined by his group.
The elaborate structural studies of proteins from several important systems as potential drug targets such as phospholipase
Phospholipase
A phospholipase is an enzyme that hydrolyzes phospholipids into fatty acids and other lipophilic substances. There are four major classes, termed A, B, C and D, distinguished by the type of reaction which they catalyze:*Phospholipase A...
A2, cyclooxygenase
Cyclooxygenase
Cyclooxygenase is an enzyme that is responsible for formation of important biological mediators called prostanoids, including prostaglandins, prostacyclin and thromboxane. Pharmacological inhibition of COX can provide relief from the symptoms of inflammation and pain...
, lipoxygenase
Lipoxygenase
Lipoxygenases are a family of iron-containing enzymes that catalyse the dioxygenation of polyunsaturated fatty acids in lipids containing a cis,cis-1,4- pentadiene structure. It catalyses the following reaction:...
, endothelin
Endothelin
Endothelins are proteins that constrict blood vessels and raise blood pressure. They are normally kept in balance by other mechanisms, but when they are over-expressed, they contribute to high blood pressure and heart disease....
receptor, endothelin converting enzyme, breast cancer
Breast cancer
Breast cancer is cancer originating from breast tissue, most commonly from the inner lining of milk ducts or the lobules that supply the ducts with milk. Cancers originating from ducts are known as ductal carcinomas; those originating from lobules are known as lobular carcinomas...
regression proteins and matrix metanosomal proteins as well as their complexes with natural and designed synthetic ligands have been carried out.
His laboratory has submitted more than 301 sets of proteins structure coordinates in the protein data bank
Protein Data Bank
The Protein Data Bank is a repository for the 3-D structural data of large biological molecules, such as proteins and nucleic acids....
(PDB) which makes it the highest number in India. Initially, he had contributed significantly on the structure - function studies of a number of antipyretic
Antipyretic
Antipyretics ; an-tee-pahy-ret-iks; from the Greek anti, against, and pyreticus, are drugs or herbs that reduce fever. Normally, they will not lower body temperature if one does not have a fever. Antipyretics cause the hypothalamus to override an interleukin-induced increase in temperature...
, analgesic
Analgesic
An analgesic is any member of the group of drugs used to relieve pain . The word analgesic derives from Greek an- and algos ....
and anti-inflammatory agents and then on antibactrial sufonamides and their derivatives. He had developed the rules of peptide design with alpha, beta – dehydro - amino acids through extensive studies using syntheses, and X-ray and NMR structure determinations. These design rules are being exploited for making specific peptides to act as tight inhibitors of target enzymes and potent antagonists of target receptors for eventually leading to useful therapeutic agents.
As part of his protein structural studies, a large number of structures of lactoferrin
Lactoferrin
Lactoferrin , also known as lactotransferrin , is a multifunctional protein of the transferrin family. Lactoferrin is a globular glycoprotein with a molecular mass of about 80 kDa that is widely represented in various secretory fluids, such as milk, saliva, tears, and nasal secretions...
proteins from various species in iron-saturated and apo-forms as well as those of its proteolytically generated monoferric functional N- and C-lobes have been determined in his laboratory through which it was demonstrated that large scale conformational changes occur in the structures of lactoferrins upon iron-binding and iron-release, cations other than ferric ion also bind to the iron-binding cleft but with lower affinity, similarly anions other than carbonate/bicarbonate can also bind with reduced potency, and bilobal lactoferrin
Lactoferrin
Lactoferrin , also known as lactotransferrin , is a multifunctional protein of the transferrin family. Lactoferrin is a globular glycoprotein with a molecular mass of about 80 kDa that is widely represented in various secretory fluids, such as milk, saliva, tears, and nasal secretions...
can be converted into two functional N-terminal and C-terminal lobes with proteinase K. It was only his group in the whole world that successfully demonstrated the proteolytic production of N- and C-terminal molecular halves of lactoferrin and determined their three-dimensional structures. These studies have provided valuable insights into the structural basis of iron-binding and iron-release in lactoferrins and their roles as antibacterial agents and in other therapeutic applications.
While carrying out enzymatic cleavage of lactoferrin proteins, a novel antifungal
Antifungal
* Antifungal medication, a medication used to treat fungal infection s such as athlete's foot , ringworm, candidiasis, etc.* Antifungal protein, a protein family* an adjective referring to a fungicide compound...
decapeptide was discovered whose excellent potency against bacterial infections has been established.
His group has carried out extensive structural studies of phospholipase
Phospholipase
A phospholipase is an enzyme that hydrolyzes phospholipids into fatty acids and other lipophilic substances. There are four major classes, termed A, B, C and D, distinguished by the type of reaction which they catalyze:*Phospholipase A...
A2 enzymes and their complexes with various natural compounds, substrate analogues, non-steroidal anti-inflammatory agents and designed peptides. The new molecules have also been designed against cyclooxygenase and lypoxygenase. The enzymes phospholipase A2, cyclooxygenase and lypoxygenase are involved in the production of pro-inflammatory compounds collectively called as eicosanoids. He has already developed several highly potent inhibitors that are under consideration for further evaluation as anti-inflammatory agents. His group has been practicing the rational approach of structure-based drug design for developing therapeutic agents against various inflammatory disorders such as rheumatism and arthritis using PLA2, COX-2 and LOX enzymes as macromolecular targets.
In yet another area of current interest, his group has determined the crystal structures of several secretory glycoproteins isolated from dry secretions of various mammalian species including humans. This is a new class of proteins, first time detected whose functions and structures were unknown. These proteins are implicated as protective signaling factors in the large scale tissue remodeling processes. Their role in the breast cancers as protective factors for the breast cancer cells makes them important targets for structure - based drug design and offers opportunities for developing new therapeutic agents against breast cancer. He has been able to design several peptides that bind to these proteins with potencies ranging up to 10-7 M. The crystal structures of the complexes of these proteins with designed peptides have helped in identifying the site of binding in this protein. The structures of the complexes with various oligosachharides have provided information about the potencies of sugar binding. It also indicated the type and nature of sugars that will bind to this class of proteins specifically. Furthermore, several crystal structures of the ternary complexes of these proteins with peptides and sugars have helped in understanding the mode of binding of these proteins to cell surface receptors.
Recently he initiated a new programme on Clinical Proteomics
Clinical Proteomics
Clinical Proteomics is a peer-reviewed medical journal published quarterly by Humana Press. covers scientific research in the field of translational proteomics with an emphasis on the application of proteomic technology to all aspects of clinical research. It was established in March 2004 and the...
in which it is intended to characterize all the proteins that are expressed during various patho/physiological conditions. The newly identified proteins will either be useful as biomarkers or they may be associated with the progression of diseases making them important targets for drug design.
He has published more than 307 research papers in the leading journals.
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|- style="background: black; color: white"
|Structure of Peptidoglycan Recognition Protein
|Structure of Lactoperoxidase
|Structure of Lactoferrin
|Structure of SPX-40>
|
|
|>
Education
Professor Tej Singh obtained his Masters in Science in first rank from the University of AllahabadAllahabad
Allahabad , or Settled by God in Persian, is a major city of India and is one of the main holy cities of Hinduism. It was renamed by the Mughals from the ancient name of Prayaga , and is by some accounts the second-oldest city in India. It is located in the north Indian state of Uttar Pradesh,...
. He started his research career in 1971 as a graduate student at the Indian Institute of Science
Indian Institute of Science
Indian Institute of Science is a research institution of higher learning located in Bangalore, India. It was established in 1909.-History:After a chance meeting between Jamsetji N...
, Bangalore
Bangalore
Bengaluru , formerly called Bengaluru is the capital of the Indian state of Karnataka. Bangalore is nicknamed the Garden City and was once called a pensioner's paradise. Located on the Deccan Plateau in the south-eastern part of Karnataka, Bangalore is India's third most populous city and...
. He obtained his Ph. D degree in the mid 70's working on the crystal structure determinations and design of anti-inflammatory analgesics for new drug discovery.
Area of Specialization
Structural Biology ; Protein Crystallography ; Rational Structure based Drug Design and Drug DiscoveryProfessional career
Soon after obtaining his Ph. D degree, he worked about a year (1977) as a lecturer at the University of Indore. He then spent more than two years (1978–1980) as an Alexander von Humboldt / Max-Planck, post doctoral fellow in the German laboratory of Professor Robert HuberRobert Huber
Robert Huber is a German biochemist and Nobel laureate.He was born 20 February 1937 in Munich where his father, Sebastian, was a bank cashier. He was educated at the Humanistisches Karls-Gymnasium from 1947 to 1956 and then studied chemistry at the Technische Hochschule, receiving his diploma in 1960...
, who later received the Nobel Prize
Nobel Prize
The Nobel Prizes are annual international awards bestowed by Scandinavian committees in recognition of cultural and scientific advances. The will of the Swedish chemist Alfred Nobel, the inventor of dynamite, established the prizes in 1895...
. After his return to India he worked as a reader at Sardar Patel University (1980–83) and an Additional Professor (1984–85) in the Department of Biophysics at the All India Institute of Medical Sciences, New Delhi. He was appointed Professor and Head of the Department in 1986, where he established a flourishing school of structural biology and new drug discovery.
Awards and honors
Goyal Prize for Life Sciences, 2010Distinguished Biotechnology Research Professor (DBT), 2009
GN Ramachandran Gold Medal for excellence in Science and Technology (CSIR), 2006
Distinguished Biotechnologist (DBT), 2006
Vice President, Indian National Science Academy, 2007–2009
JC Bose Memorial Award, 2005
Alexander von Humboldt Fellow, 1977
Canadian Development Agency Award, 1999
Fellow of the Indian Academy of Sciences, 1994
Fellow of the National Academy of Sciences, 1998
Fellow of the Indian National Science Academy, 2000 -
Fellow of the Third World Academy of Sciences : F.T.W.A.S. 2003 -
Member of the Commission on Biological Macromolecules of the International Union of Crystallography (IUCr) (2005–2008)
Executive member of the International Union of Pure and Applied Biophysics (IUPAB) (2002–2005)
Member Secretary of the INSA National Committee for IUPAB (1988–91)
Member of the INSA National Committee for International Union of Pure and Applied Biophysics (IUPAB) (1985–88)
Member of the INSA National Committee for International Union of Crystallography (IUCr) (2000–2003)
Ex-officio member of the Joint National Committee of INSA for IUPAB and IUCr (2002–2005) , (2005–2008)
Member of a committee to select fellows for Indian National Science Academy (2001–2003)
Member of the Committee to select fellows for the Indian Academy of Sciences, 2005
Member of the Indian Biophysical Society since 1977
Member of the Society of Biological Chemists of India , 1982
Vice President of the Indian Biophysical society (1994–1996)
Member of the American Society for Biochemistry and Molecular Biology (ASBMB), since 2000
Member Technology Development Board on Pharmaceutical Industry (2002)
Member of the Senate of Indian Institute of Technology Delhi, (2001–2002)
Chairman of the DST Committee for the Fast Track Programme in life Sciences (2002–2004) , (2005–2007)
Member of the Apex Committee of the DBT for the programme support at I.I.Sc. Bangalore (1998–2001), (2002–2004) , (2005–2008)
Member of the Programme Advisory Committee of DST on Biochemistry, Biophysics, Molecular Biology including Microbiology (1996–1998) , (1999–2001)
Member of the DBT task force on Basic Biology / Modern Biology (1996–1998) , (1999–2001)
Member of the DBT task force on Infrastructure (2001–2003) , (2004–2006) , (2006–2008)
Member of the DBT task force on Bioinformatics (1994–1996)
Member of the Advisory Committee of Biotechnology Teaching Programme of the Biotechnology Centre, JNU (2002)
Member of the Executive Committee of the Bioinformatics Centre at Madurai Kamraj University (2002–2003)
Member of the Academic Committee of the Biotechnology Unit of AMU, Aligarh (2004–2006)
Member of the Research Area Panel of the National Institute of Immunology (1994–1996)
Member of the Special Committee of the School of Life Sciences, JNU (1988–1990) , (1991–1993)
Member of the Special Committee of the Centre for Biotechnology, JNU (1991–1993) , (1994–1996) , (1997–1999) , (2000–2002) , (2003–2005)
Member of the Special Committee of the Special Centre of Molecular Medicine, JNU (2001–2003) , (2004–2006)
Member of the Special Committee of the School of Environmental Sciences, JNU (2001–2003) , (2004–2006)
Member of the Academic Committee of the Nuclear Science Centre, New Delhi, (2002–2004), (2004–2006)
Member of the Academic Committee of Central Drug Research Institute, Lucknow, (2005–2006)
Member of the Academic Committee of the Institute of Microbial Technology, Chandigarh, (2005–2006)
Member of the Executive Council of the Centre of Bioinformatics, Institute of Microbial Technology, Chandigarh, 2005
Member of the Academic Council of the Central Unversityof Hyderabad, 2006–2007
Executive member of the Council of the International Union of Pure and Applied Biophysics (IUPAB) (2005–2008)
K.K.Foundation National Award for Science and Technology, 2001
Chairman of the Fast-Track Programme of DST in Life Sciences, 2001–2003
Member of the Technology Development Board on Pharmaceutical Industry, 2002–2003
Executive member of the Council of International Union of Pure and Applied Biophysics, 2002–2005
Max-Planck - Humbodt Award - 1999
Canadian Development Agency Award - 1991
Danish International Development Agency Award - 1978
First Rank in M.Sc. in the University of Allahabad - 1971
External links
- http://dst.gov.in/whats_new/press-release07/biotech-award.htm
- http://www.jbc.org/cgi/reprint/M208967200v1.pdf
- http://timesofindia.indiatimes.com/articleshow/753224.cms
- http://www.bio-medicine.org/medicine-news/Five-New-Anti-Inflammatory-Compounds-Produced-By-Indian-Scientists-6838-1/
- http://pib.nic.in/release/release.asp?relid=25773