J. Jarrett - Academia.edu (original) (raw)

Uploads

Papers by J. Jarrett

Research paper thumbnail of Seeding “one-dimensional crystallization” of amyloid: A pathogenic mechanism in Alzheimer's disease and scrapie?

Cell, 1993

Alzheimer's disease (AD) is a neurodegenerative disease characterized by the presence of cerebral... more Alzheimer's disease (AD) is a neurodegenerative disease characterized by the presence of cerebral amyloid plaque (reviewed by Selkoe, 1991), a highly ordered protein ag

Research paper thumbnail of Crystal Structure of Biotin Synthase, an S-Adenosylmethionine-Dependent Radical Enzyme

Science, 2004

The crystal structure of biotin synthase from Escherichia coli in complex with S-adenosyl-Lmethio... more The crystal structure of biotin synthase from Escherichia coli in complex with S-adenosyl-Lmethionine and dethiobiotin has been determined to 3.4 angstrom resolution. This structure addresses how "AdoMet radical" or "radical SAM" enzymes use Fe 4 S 4 clusters and S-adenosyl-L-methionine to generate organic radicals. Biotin synthase catalyzes the radical-mediated insertion of sulfur into dethiobiotin to form biotin. The structure places the substrates between the Fe 4 S 4 cluster, essential for radical generation, and the Fe 2 S 2 cluster, postulated to be the source of sulfur, with both clusters in unprecedented coordination environments.

Research paper thumbnail of The generation of 5′-deoxyadenosyl radicals by adenosylmethionine-dependent radical enzymes

Current Opinion in Chemical Biology, 2003

Adenosylmethionine-dependent radical enzymes provide a novel mechanism for generating the highly ... more Adenosylmethionine-dependent radical enzymes provide a novel mechanism for generating the highly oxidizing 5 0 -deoxyadenosyl radical in an anaerobic reducing environment. Recent studies suggest a unique covalent interaction between adenosylmethionine and a catalytic iron-sulfur cluster that may promote inner-sphere electron transfer to the sulfonium, resulting in the reductive cleavage of a C-S bond and the generation of a 5 0 -deoxyadenosyl radical. The utilization of this radical as a catalytic and stoichiometric oxidant in many different enzyme reactions reflects the broad diversity of radical enzymes throughout biology.

Research paper thumbnail of Biotin SynthaseEnzyme or Reactant?

Chemistry & Biology, 2005

His 6 -!AccB can be quantified on the same gel using either Western blots or ( 35 S)-methionine i... more His 6 -!AccB can be quantified on the same gel using either Western blots or ( 35 S)-methionine incorporation, and the ratio gives 20-60 equivalents of biotin pro-Biotin synthase catalyzes formation of a thiophane duced per initial biotin synthase monomer. Although a ring through a radical mechanism that is difficult to true kinetic analysis is premature, 20 turnovers obreconstitute in vitro. Choi-Rhee and Cronan [1] measerved in 4 hr gives a minimum turnover number of sure a turnover of 20-60 equivalents of biotin in vivo, w0.08 min −1 , essentially equivalent to the maximal rate but also find that turnover renders the protein susof w0.07 min −1 for one turnover observed in vitro [4]. ceptible to proteolytic destruction.

Research paper thumbnail of Characterization of Nonradioactive Assays for Cobalamin-Dependent and Cobalamin-Independent Methionine Synthase Enzymes

Analytical Biochemistry, 1995

The user has requested enhancement of the downloaded file.

Research paper thumbnail of Studies related to a convergent fragment-coupling approach to peptide synthesis using the Kaiser oxime resin

The Journal of Organic Chemistry, 1992

In our efforta to synthesize the @-amyloid protein of Alzheimer's dieease and other amyloid-... more In our efforta to synthesize the @-amyloid protein of Alzheimer's dieease and other amyloid-forming peptides, we have used a convergent solid-phase fragment Coupling strategy employing the p-nitrobenzophenone oxime resin developed by ET Kaiser.'J The Kaiser oxime resin's ...

Research paper thumbnail of Seeding “one-dimensional crystallization” of amyloid: A pathogenic mechanism in Alzheimer's disease and scrapie?

Cell, 1993

Alzheimer's disease (AD) is a neurodegenerative disease characterized by the presence of cerebral... more Alzheimer's disease (AD) is a neurodegenerative disease characterized by the presence of cerebral amyloid plaque (reviewed by Selkoe, 1991), a highly ordered protein ag

Research paper thumbnail of Crystal Structure of Biotin Synthase, an S-Adenosylmethionine-Dependent Radical Enzyme

Science, 2004

The crystal structure of biotin synthase from Escherichia coli in complex with S-adenosyl-Lmethio... more The crystal structure of biotin synthase from Escherichia coli in complex with S-adenosyl-Lmethionine and dethiobiotin has been determined to 3.4 angstrom resolution. This structure addresses how "AdoMet radical" or "radical SAM" enzymes use Fe 4 S 4 clusters and S-adenosyl-L-methionine to generate organic radicals. Biotin synthase catalyzes the radical-mediated insertion of sulfur into dethiobiotin to form biotin. The structure places the substrates between the Fe 4 S 4 cluster, essential for radical generation, and the Fe 2 S 2 cluster, postulated to be the source of sulfur, with both clusters in unprecedented coordination environments.

Research paper thumbnail of The generation of 5′-deoxyadenosyl radicals by adenosylmethionine-dependent radical enzymes

Current Opinion in Chemical Biology, 2003

Adenosylmethionine-dependent radical enzymes provide a novel mechanism for generating the highly ... more Adenosylmethionine-dependent radical enzymes provide a novel mechanism for generating the highly oxidizing 5 0 -deoxyadenosyl radical in an anaerobic reducing environment. Recent studies suggest a unique covalent interaction between adenosylmethionine and a catalytic iron-sulfur cluster that may promote inner-sphere electron transfer to the sulfonium, resulting in the reductive cleavage of a C-S bond and the generation of a 5 0 -deoxyadenosyl radical. The utilization of this radical as a catalytic and stoichiometric oxidant in many different enzyme reactions reflects the broad diversity of radical enzymes throughout biology.

Research paper thumbnail of Biotin SynthaseEnzyme or Reactant?

Chemistry & Biology, 2005

His 6 -!AccB can be quantified on the same gel using either Western blots or ( 35 S)-methionine i... more His 6 -!AccB can be quantified on the same gel using either Western blots or ( 35 S)-methionine incorporation, and the ratio gives 20-60 equivalents of biotin pro-Biotin synthase catalyzes formation of a thiophane duced per initial biotin synthase monomer. Although a ring through a radical mechanism that is difficult to true kinetic analysis is premature, 20 turnovers obreconstitute in vitro. Choi-Rhee and Cronan [1] measerved in 4 hr gives a minimum turnover number of sure a turnover of 20-60 equivalents of biotin in vivo, w0.08 min −1 , essentially equivalent to the maximal rate but also find that turnover renders the protein susof w0.07 min −1 for one turnover observed in vitro [4]. ceptible to proteolytic destruction.

Research paper thumbnail of Characterization of Nonradioactive Assays for Cobalamin-Dependent and Cobalamin-Independent Methionine Synthase Enzymes

Analytical Biochemistry, 1995

The user has requested enhancement of the downloaded file.

Research paper thumbnail of Studies related to a convergent fragment-coupling approach to peptide synthesis using the Kaiser oxime resin

The Journal of Organic Chemistry, 1992

In our efforta to synthesize the @-amyloid protein of Alzheimer's dieease and other amyloid-... more In our efforta to synthesize the @-amyloid protein of Alzheimer's dieease and other amyloid-forming peptides, we have used a convergent solid-phase fragment Coupling strategy employing the p-nitrobenzophenone oxime resin developed by ET Kaiser.'J The Kaiser oxime resin's ...

Log In