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Cells and Sulfur: Strategies for Using a Versatile Element

Cells and Sulfur
Reported by
Megan Stephan

Posted March 27, 2007


Sulfur is an important component of biological molecules, especially for proteins, where sulfur is essential for the synthesis of the amino acids cysteine and methionine. Cysteine in particular plays a key role in protein structure and function, forming structurally important disulfide bonds and contributing a unique functionality to enzymes' active sites.

For living organisms to use sulfate, they have had to come up with biochemical strategies to activate it so that it can participate in chemical reactions. These strategies were the subject of discussion at the October 4, 2006, meeting of the Chemical Biology Discussion Group.

Topics discussed included ATP sulfurylases, the enzymes used by many organisms to activate sulfate using the metabolic energy stored in ATP and other nucleotide triphosphates; the biosynthesis of the vitamin thiamin; how sulfur metabolism contributes to the pathogenicity of the tuberculosis-causing organism Mycobacterium tuberculosis; and the structure and regulation of estrogen sulfotransferase, an enzyme that sulfonates the hormone estrogen in humans and other mammals.

Use the tabs above to find a meeting report and multimedia from this event.

Web Sites

KEGG Reference Pathway for Sulfur Metabolism
Kyoto Encyclopedia of Genes and Genomes site includes links to sulfur metabolism pathways from various organisms.

The Sulfur Cycle
Graphic illustration depicting how sulfur cycles between living organisms and the environment.

Linus Pauling Institute page on the functions of thiamin.

A Tribute to Sulfur
Review article on sulfur biology from the European Journal of Biochemistry.

Fact sheet from the Centers for Disease Control and Prevention.

Journal Articles

The Catalytic Manipulation of Sulfur and Half-Site Reactivity of Estrogen Sulfotransferase

Hoff RH, Czyryca PG, Sun M, et al. 2006. Transition state of the sulfuryl transfer reaction of estrogen sulfotransferase. J. Biol. Chem. 281: 30645-30649.

Lalor DJ, Schnyder T, Saridakis V, et al. 2003. Structural and functional analysis of a truncated form of Saccharomyces cerevisiae ATP sulfurylase: C-terminal domain essential for oligomer formation but not for activity. Protein Eng. 16: 1071-1079. Full Text

Pilloff DE, Leyh TS. 2003. Allosteric and catalytic functions of the PPi-binding motif in the ATP sulfurylase-GTPase system. J. Biol. Chem. 278: 50435-50441. Full Text

Pinto R, Tang QX, Britton WJ, et al. 2004. The Mycobacterium tuberculosis cysD and cysNC genes form a stress-induced operon that encodes a tri-functional sulfate-activating complex. Microbiology 150: 1681-1686. Full Text

Sun M, Andreassi JL II, Liu S, et al. 2005. The trifunctional sulfate-activating complex (SAC) of Mycobacterium tuberculosis. J. Biol. Chem. 280: 7861-7866. Full Text

Sun M, Leyh TS. 2005. Anatomy of an energy-coupling mechanism—the interlocking catalytic cycles of the ATP sulfurylase-GTPase system. Biochemistry 44: 13941-13948. (PDF, 112 KB) Full Text

Sun M, Leyh TS. 2006. Channeling in sulfate activating complexes. Biochemistry 45: 11304-11311.

Thiamin: A Simple Vitamin with a Complex Biosynthetic Pathway

Begley TP. 2006. Cofactor biosynthesis: an organic chemist's treasure trove. Nat. Prod. Rep. 23: 15-25. Full Text

Burns KE, Baumgart S, Dorrestein PC, et al. 2005. Reconstitution of a new cysteine biosynthetic pathway in Mycobacterium tuberculosis. J. Am. Chem. Soc. 127: 11602-11603. (PDF, 61 KB) Full Text

Chatterjee A, Jurgenson CT, Schroeder FC, et al. 2006. Thiamin biosynthesis in eukaryotes: characterization of the enzyme-bound product of thiazole synthase from Saccharomyces cerevisiae and its implications in thiazole biosynthesis. J. Am. Chem. Soc. 128: 7158-7159.

Dorrestein PC, Zhai H, McLafferty FW, et al. 2004. The biosynthesis of the thiazole phosphate moiety of thiamin: the sulfur transfer mediated by the sulfur carrier protein ThiS. Chem. & Biol. 11: 1373-1381. Full Text

Lehmann C, Begley TP, Ealick SE. 2006. Structure of the Escherichia coli ThiS-ThiF complex, a key component of the sulfur transfer system in thiamin biosynthesis. Biochemistry 45: 11-19.

Wang C, Xi J, Begley TP, et al. 2001. Solution structure of ThiS and implications for the evolutionary roots of ubiquitin. Nat. Struct. Biol. 8: 47-51. (PDF, 857 KB) Full Text

Xi J, Ge Y, Kinsland C, et al. 2001. Biosynthesis of the thiazole moiety of thiamin in Escherichia coli: Identification of an acyldisulfide-linked protein-protein conjugate that is functionally analogous to the ubiquitin/E1 complex. Proc. Natl Acad. Sci. USA 98: 8513-8518. Full Text

Reducing the Mysteries of Sulfur Metabolism in Mycobacterium tuberculosis

Carroll KS, Gao H, Chen HY, et al. 2005. Investigation of the iron-sulfur cluster in Mycobacterium tuberculosis APS reductase: implications for substrate binding and catalysis. Biochemistry 44: 14647-14657. Full Text

Carroll KS, Gao H, Chen HY, et al. 2005. A conserved mechanism for sulfonucleotide reduction. PLoS Biol. 3: 1418-1435. Full Text

Chartron J, Carroll KS, Shiau C. 2006. Substrate recognition, protein dynamics, and iron-sulfur cluster in Pseudomonas aeruginosa adenosine 5′-phosphosulfate reductase. J. Mol. Biol. 364: 152-169. Full Text

Gao H, Leary J, Carroll KS, et al. 2007. Noncovalent complexes of APS reductase from M. tuberculosis: delineating a mechanistic model using ESI-FTICR MS. J. Am. Soc. Mass Spectrom. 18: 167-178

Kraut DA, Carroll KS & Herschlag D. 2003. Challenges in enzyme mechanism and energetics. Annu. Rev. Biochem. 72: 517-571.


Thomas S. Leyh, PhD

Albert Einstein College of Medicine
e-mail | publications

Thomas Leyh is a professor of biochemistry at the Einstein College of Medicine. He is a mechanistic enzymologist with a long-standing interest in sulfur biochemistry, GTPase function, and the conformational coupling of energetics. His group has demonstrated that enzymes in the cysteine biosynthetic pathway self-organize into a multifunctional protein complex, out of which emerges new catalytic function that orchestrates the activities of the complex. He completed his PhD in biophysics at the University of Pennsylvania

Tadhg P. Begley, PhD

Cornell University
e-mail | web site | publications

Tadhg Begley is professor of chemistry and chemical biology at Cornell University, Ithaca, New York. He received his BSc from University College Cork and his PhD from the California Institute of Technology. He carried out postdoctoral studies at the University of Geneva and at MIT before joining the Cornell faculty in 1986.

Begley's research is focused on the mechanistic enzymology of complex organic transformations, particularly those found on the vitamin biosynthetic pathways. He is currently working on the biosynthesis of NAD, thiamin, and pyridoxal phosphate.

Begley is a member of the editorial boards for Molecular BioSystems, Vitamins and Hormones, Bioorganic Chemistry, Chemical Biology & Drug Design, Comprehensive Natural Products Chemistry II, and the Wiley Encyclopedia of Chemical Biology. He recently coauthored The Organic Chemistry of Biological Pathways with John McMurry.

Kate S. Carroll, PhD

University of Michigan
e-mail | web site | publications

Kate Carroll investigates the role that sulfur-containing metabolites play in the replication and persistence of Mycobacteria. The biosynthetic machinery associated with these critical metabolites may offer new targets for anti-tuberculosis therapy. In addition, Carroll is also developing new chemical tools to identify and study oxidative post-translational modifications associated with aging and neurodegenerative diseases.

Carroll joined the Life Sciences Institute at the University of Michigan in summer 2006 as an assistant research professor, and will also be an assistant professor of chemistry in the College of Literature, Science, and the Arts. She completed her Damon Runyon postdoctoral fellowship in chemistry at the University of California, Berkeley. A California native, she received her undergraduate degree in biochemistry and molecular biology from Mills College and her PhD in biochemistry from Stanford University.

Meihao Sun, PhD

Albert Einstein College of Medicine

Meihao Sun is an associate in the biochemistry department of Albert Einstein College of Medicine. He is working on sulfur metabolism in different organisms, especially focusing on sulfate activation and sulfuryl group transfer.

Sun received his PhD in plant science from the Institute of Plant Physiology and Ecology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences. He did his postdoctoral training in enzymology in Thomas Leyh's lab at Albert Einstein College of Medicine.

Megan Stephan

Megan Stephan studied transporters and ion channels at Yale University for nearly two decades before giving up the pipettor for the pen. She specializes in covering research at the interface between biology, chemistry, and physics. Her work has appeared in The Scientist and Yale Medicine. Stephan holds a PhD in biology from Boston University.