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K. V. Rajagopalan

James B. Duke Distinguished Professor Emeritus of Medicine
Biochemistry
Box 3711 Med Ctr, Durham, NC 27710
225A Nanaline H Duke, Durham, NC 27708

Featured Works


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 Cite

Essential 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 Cite

Mechanistic 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 Cite

The 1.2 A structure of the human sulfite oxidase cytochrome b(5) domain.

Journal article Acta Crystallogr D Biol Crystallogr · July 2003 Featured Publication The molybdenum- and iron-containing enzyme sulfite oxidase catalyzes the physiologically vital oxidation of sulfite to sulfate. Sulfite oxidase contains three domains: an N-terminal cytochrome b(5) domain, a central domain harboring the molybdenum cofactor ... Full text Link to item Cite

Recombinant Rhodobacter capsulatus xanthine dehydrogenase, a useful model system for the characterization of protein variants leading to xanthinuria I in humans.

Journal article J Biol Chem · June 6, 2003 Featured Publication Rhodobacter capsulatus xanthine dehydrogenase (XDH) forms an (alphabeta)2 heterotetramer and is highly homologous to homodimeric eukaryotic XDHs. The crystal structures of bovine XDH and R. capsulatus XDH showed that the two proteins have highly similar fo ... Full text Link to item Cite

Mechanistic and mutational studies of Escherichia coli molybdopterin synthase clarify the final step of molybdopterin biosynthesis.

Journal article J Biol Chem · April 18, 2003 Featured Publication Biosynthesis of the molybdenum cofactor, a chelate of molybdenum or tungsten with a novel pterin, occurs in virtually all organisms including humans. In the cofactor, the metal is complexed to the unique cis-dithiolene moiety located on the pyran ring of m ... Full text Link to item Cite

Structural studies of molybdopterin synthase provide insights into its catalytic mechanism.

Journal article J Biol Chem · April 18, 2003 Featured Publication Molybdenum cofactor biosynthesis is an evolutionarily conserved pathway present in eubacteria, archaea, and eukaryotes, including humans. Genetic deficiencies of enzymes involved in cofactor biosynthesis in humans lead to a severe and usually fatal disease ... Full text Link to item Cite

Role of conserved tyrosine 343 in intramolecular electron transfer in human sulfite oxidase.

Journal article J Biol Chem · January 31, 2003 Featured Publication Tyrosine 343 in human sulfite oxidase (SO) is conserved in all SOs sequenced to date. Intramolecular electron transfer (IET) rates between reduced heme (Fe(II)) and oxidized molybdenum (Mo(VI)) in the recombinant wild-type and Y343F human SO were measured ... Full text Link to item Cite

Pulsed EPR studies of the exchangeable proton at the molybdenum center of dimethyl sulfoxide reductase.

Journal article J Biol Inorg Chem · January 2003 Featured Publication Electron spin echo envelope modulation (ESEEM) spectroscopy has been used to determine the hyperfine ( hfi) and quadrupole ( nqi) interactions of the exchangeable deuteron (proton) at the Mo(V) site of DMSO reductase. The data obtained have been translated ... Full text Link to item Cite

Escherichia coli MoeA and MogA. Function in metal incorporation step of molybdenum cofactor biosynthesis.

Journal article J Biol Chem · July 12, 2002 Featured Publication Escherichia coli MoeA and MogA are required for molybdenum cofactor biosynthesis and are believed to function in the addition of molybdenum to the dithiolene of molybdopterin to form molybdenum cofactor. Here we show that moeA(-) and mogA(-) cells are able ... Full text Link to item Cite

Isolated sulfite oxidase deficiency: identification of 12 novel SUOX mutations in 10 patients.

Journal article Hum Mutat · July 2002 Featured Publication We report twelve novel mutations in patients with isolated sulfite oxidase deficiency. The mutations are in SUOX, the gene that encodes the molybdohemoprotein sulfite oxidase. These include two frameshift mutations, a four-basepair deletion (562del4) and a ... Full text Link to item Cite

Isolated sulfite oxidase deficiency: mutation analysis and DNA-based prenatal diagnosis.

Journal article Prenat Diagn · May 2002 Featured Publication Isolated sulfite oxidase deficiency is an autosomal recessive, neurological disorder resulting from a defect in SUOX, the gene encoding the enzyme that catalyzes the terminal reaction in the sulfur amino acid degradation pathway. In its classical, severe f ... Full text Link to item Cite

Crystal structures of the active and alloxanthine-inhibited forms of xanthine dehydrogenase from Rhodobacter capsulatus.

Journal article Structure · January 2002 Featured Publication Xanthine dehydrogenase (XDH), a complex molybdo/iron-sulfur/flavoprotein, catalyzes the oxidation of hypoxanthine to xanthine followed by oxidation of xanthine to uric acid with concomitant reduction of NAD+. The 2.7 A resolution structure of Rhodobacter c ... Full text Link to item Cite

Molybdopterin synthase mutations in a mild case of molybdenum cofactor deficiency.

Journal article Am J Med Genet · November 22, 2001 Featured Publication Molybdenum cofactor deficiency is a rare inborn error of metabolism with generally severe symptoms, most often including neonatal seizures and severe developmental delay. We describe a patient with an unusually mild form of the disease. Two mutations in MO ... Full text Link to item Cite

Mechanism of ubiquitin activation revealed by the structure of a bacterial MoeB-MoaD complex.

Journal article Nature · November 15, 2001 Featured Publication The activation of ubiquitin and related protein modifiers is catalysed by members of the E1 enzyme family that use ATP for the covalent self-attachment of the modifiers to a conserved cysteine. The Escherichia coli proteins MoeB and MoaD are involved in mo ... Full text Link to item Cite

Characterization of Escherichia coli MoeB and its involvement in the activation of molybdopterin synthase for the biosynthesis of the molybdenum cofactor.

Journal article J Biol Chem · September 14, 2001 Featured Publication Amino acid sequence comparisons of Escherichia coli MoeB suggested that the MoeB-dependent formation of a C-terminal thiocarboxylate on the MoaD subunit of molybdopterin synthase might resemble the ubiquitin-activating step in the ubiquitin-targeted degrad ... Full text Link to item Cite

A sulfurtransferase is required in the transfer of cysteine sulfur in the in vitro synthesis of molybdopterin from precursor Z in Escherichia coli.

Journal article J Biol Chem · June 22, 2001 Featured Publication It has been shown that conversion of precursor Z to molybdopterin (MPT) by Escherichia coli MPT synthase entails the transfer of the sulfur atom of the C-terminal thiocarboxylate from the small subunit of the synthase to generate the dithiolene group of MP ... Full text Link to item Cite

An active site tyrosine influences the ability of the dimethyl sulfoxide reductase family of molybdopterin enzymes to reduce S-oxides.

Journal article J Biol Chem · April 20, 2001 Featured Publication Dimethyl sulfoxide reductase (DMSOR), trimethylamine-N-oxide reductase (TMAOR), and biotin sulfoxide reductase (BSOR) are members of a class of bacterial oxotransferases that contain the bis(molybdopterin guanine dinucleotide)molybdenum cofactor. The prese ... Full text Link to item Cite

In vitro incorporation of nascent molybdenum cofactor into human sulfite oxidase.

Journal article J Biol Chem · January 19, 2001 Featured Publication We were able to reconstitute molybdopterin (MPT)-free sulfite oxidase in vitro with the molybdenum cofactor (Moco) synthesized de novo from precursor Z and molybdate. MPT-free human sulfite oxidase apoprotein was obtained by heterologous expression in an E ... Full text Link to item Cite

Crystal structure of molybdopterin synthase and its evolutionary relationship to ubiquitin activation.

Journal article Nat Struct Biol · January 2001 Featured Publication Molybdenum cofactor (Moco) biosynthesis is an evolutionarily conserved pathway present in eubacteria, archaea and eukaryotes, including humans. Genetic deficiencies of enzymes involved in Moco biosynthesis in humans lead to a severe and usually fatal disea ... Full text Link to item Cite

Molybdopterin from molybdenum and tungsten enzymes.

Journal article Adv Protein Chem · 2001 Featured Publication Full text Link to item Cite