Overview
Research Abstract
The research in our laboratory deals with the chemistry and biology of enzymes in which the element molybdenum is an essential constituent. Recent studies in the laboratory have led to the discovery and characterization of a novel prosthetic group, called molybdopterin, shown to be present in all Mo-containing enzymes (except nitrogenase) and is intimately involved in the catalytic activity associated with the molybdenum centers of the enzymes. More recently molybdopterin has been shown to be present in tungsten containing enzymes from hyperthermophilic archaea. A human genetic deficiency in which the patients display combined deficiencies of all molybdoenzyme activities and suffer from severe neuropathology leading to childhood death has been characterized as resulting from lesions in the biosynthesis of molybdopterin. Current research is directed at areas such as the pathway of biosynthesis of molybdopterin in bacteria and in humans, structural and chemical aspects of the interaction of molybdopterin with molybdoenzymes, and the use of cloned native and mutant genes of molybdoenzymes in structure-function studies of the Mo ligand field and electron transfer reactions in the enzymes. Many of these studies involve the use of techniques such as UV-Visible, fluorescence, EPR, NMR and laser Raman spectroscopies.
The research in our laboratory deals with the chemistry and biology of enzymes in which the element molybdenum is an essential constituent. Recent studies in the laboratory have led to the discovery and characterization of a novel prosthetic group, called molybdopterin, shown to be present in all Mo-containing enzymes (except nitrogenase) and is intimately involved in the catalytic activity associated with the molybdenum centers of the enzymes. More recently molybdopterin has been shown to be present in tungsten containing enzymes from hyperthermophilic archaea. A human genetic deficiency in which the patients display combined deficiencies of all molybdoenzyme activities and suffer from severe neuropathology leading to childhood death has been characterized as resulting from lesions in the biosynthesis of molybdopterin. Current research is directed at areas such as the pathway of biosynthesis of molybdopterin in bacteria and in humans, structural and chemical aspects of the interaction of molybdopterin with molybdoenzymes, and the use of cloned native and mutant genes of molybdoenzymes in structure-function studies of the Mo ligand field and electron transfer reactions in the enzymes. Many of these studies involve the use of techniques such as UV-Visible, fluorescence, EPR, NMR and laser Raman spectroscopies.
Current Appointments & Affiliations
James B. Duke Distinguished Professor Emeritus of Medicine
·
2010 - Present
Biochemistry,
Basic Science Departments
Professor Emeritus of Biochemistry
·
2010 - Present
Biochemistry,
Basic Science Departments
Recent Publications
The role of tyrosine 343 in substrate binding and catalysis by human sulfite oxidase.
Journal Article J Biol Chem · April 9, 2004 Featured Publication In the crystal structure of chicken sulfite oxidase, the residue Tyr(322) (Tyr(343) in human sulfite oxidase) was found to directly interact with a bound sulfate molecule and was proposed to have an important role in mediating the substrate specificity and ... Full text Link to item CiteEssential role of conserved arginine 160 in intramolecular electron transfer in human sulfite oxidase.
Journal Article Biochemistry · October 28, 2003 Featured Publication Arginine 160 in human sulfite oxidase (SO) is conserved in all SO species sequenced to date. Previous steady-state kinetic studies of the R160Q human SO mutant showed a remarkable decrease in k(cat)/K(m)(sulfite) of nearly 1000-fold, which suggests that Ar ... Full text Link to item CiteMechanistic studies of human molybdopterin synthase reaction and characterization of mutants identified in group B patients of molybdenum cofactor deficiency.
Journal Article J Biol Chem · July 11, 2003 Featured Publication Biosynthesis of the molybdenum cofactor involves the initial formation of precursor Z, its subsequent conversion to molybdopterin (MPT) by MPT synthase, and attachment of molybdenum to the dithiolene moiety of MPT. The sulfur used for the formation of the ... Full text Link to item CiteRecent Grants
Structure And Function Of Enzymes--Role Of Metals
ResearchPrincipal Investigator · Awarded by National Institutes of Health · 1977 - 2009Structure And Function Of Enzymes--Role Of Metals
ResearchPrincipal Investigator · Awarded by National Institutes of Health · 1977 - 2008Molybdenum and the Molybdenum Cofactor in Health
ResearchPrincipal Investigator · Awarded by National Institutes of Health · 1990 - 2005View All Grants
Education, Training & Certifications
University of Madras (India) ·
1957
Ph.D.
University of Madras (India) ·
1954
M.S.
University of Madras (India) ·
1951
B.S.