a conserved mechanism for sulfonucleotide reduction减少sulfonucleotide的保护机制.pdfVIP

Open access, freely available online PLoS BIOLOGY A Conserved Mechanism for Sulfonucleotide Reduction 1 1,2 3 4 2 1,2,5* Kate S. Carroll , Hong Gao , Huiyi Chen , C. David Stout , Julie A. Leary , Carolyn R. Bertozzi 1 Department of Chemistry, University of California, Berkeley, California, United States of America, 2 Departments of Chemistry and Molecular Cell Biology, Genome Center, University of California, Davis, California, United States of America, 3 Department of Molecular and Cell Biology, University of California, Berkeley, California, United States of America, 4 Department of Molecular Biology, The Scripps Research Institute, La Jolla, California, United States of America, 5 Howard Hughes Medical Institute, University of California, Berkeley, California, United States of America Sulfonucleotide reductases are a diverse family of enzymes that catalyze the first committed step of reductive sulfur assimilation. In this reaction, activated sulfate in the context of adenosine-59-phosphosulfate (APS) or 39- phosphoadenosine 59-phosphosulfate (PAPS) is converted to sulfite with reducing equivalents from thioredoxin. The sulfite generated in this reaction is utilized in bacteria and plants for the eventual production of essential biomolecules such as cysteine and coenzyme A. Humans do not possess a homologous metabolic pathway, and thus, these enzymes represent attractive targets for therapeutic intervention. Here we studied the mechanism of sulfonucleotide reduction by APS reductase from the human pathogen Mycobacterium tuberculosis, using a combination of mass spectrometry and biochemical approaches. The results support the hypothesis of a two-step mechanism in which the su