July 2010

Meeting Theme: Structure, Mechanism and Regulation in Enzyme Catalysis

Structure, Mechanism and Regulation in Enzyme Catalysis

Session: Metals and Redox Chemistry
 Characterization of Two Reaction Intermediates in the Nonheme-Fe(II)-dependent Enzyme Isopenicillin N-Synthase, Carsten Krebs, The Pennsylvania State University

Methane Oxidation by an Integral Membrane Metalloenzyme, Amy C. Rosenzweig, Northwestern University

Structural and Mechanistic Studies on Peptidylglycine Alpha-amidating Enzyme, L. Mario Amzel, Johns Hopkins University School of Medicine

Session: Sulfur Chemistry and Biological Redox

 Radical-dependent Mechanisms of Post-translational Modification, Squire J. Booker, The Pennsylvania State University

Painting the Cysteine Chapel: New Tools to Probe Oxidation Biology, Kate S. Carroll, University of Michigan

Sensing Sulfur Status in Plants: Biochemical Integration of Multiple Inputs, Joseph Jez, Washington University, St. Louis

Session: Processive Enzymes
 Molecular Origami in Nature, Shiou-Chuan (Sheryl) Tsai, University of California, Irvine

Polyketide Megasynthases from Filamentous Fungi, Yi Tang, University of California, Los Angeles

Mycobacterial Polyketide Virulence Factors: Biosynthesis and Inhibition, Luis E. N. Quadri, Brooklyn College, The City University of New York

Session: Kinases, Phosphatases, and Phosphorus in Biological Reactions
 Evolution of a Robust Catalytic Scaffold for Hydrolytic Cleavage of Phosphate Ester Metabolites, Debra Dunaway-Mariano, University of New Mexico

Bivalent Inhibitors of Protein Kinases, Dustin J. Maly, University of Washington, Seattle

Computational Studies of Protein Kinases, J. Andrew McCammon, Investigator, Howard Hughes Medical Institute, University of California, San Diego

Sulfur Chemistry

The session on sulfur chemistry and biological redox, chaired by Carsten Krebs, features three diverse lectures highlighting the unique reactivity of the sulfur atom and its importance in biochemistry. Squire J. Booker (The Pennsylvania State University) will deliver a lecture, titled “Radical-dependent Mechanisms of Post-translational Modification,” in which he will describe several novel modifications of proteins that involve the insertion of sulfur atoms into unactivated C–H bonds. These reactions are considered to be the anaerobic counterpart to some of the reactions discussed in the session “Metals and Redox Chemistry,” involving activated forms of sulfur rather than dioxygen.

The lecture by Kate S. Carroll (University of Michigan), titled “Painting the Cysteine Chapel: New Tools to Probe Oxidation Biology,” will detail new proteomic approaches for detecting modifications occurring on sulfur-containing amino acid residues, which has great impact in the ability to sense cellular oxidative stress.

Joseph Jez (Washington University. St. Louis) will give a lecture, titled “Sensing Sulfur Status in Plants: Biochemical Integration of Multiple Inputs,” detailing mechanisms by which plants regulate their sulfur and thiol concentrations.

Processive Enzymes

Debra Dunaway-Mariano will chair a session on processive enzymes. This session does not include the classical nucleic acid polymerases that are discussed in other events of the meeting. Shiou-Chuan (Sheryl) Tsai (University of California, Irvine), under the title “Molecular Origami in Nature,” will present structural and mechanistic data on natural polyketide synthases, as well as systems based on this chemistry that can be used to synthesize novel polyketides. Fungal polyketide synthases will be discussed by Yi Tang (University of California, Los Angeles) in a lecture titled “Polyketide Megasynthases from Filamentous Fungi.” Luis E. N. Quadri (Brooklyn College, The City University of New York) will present his results on the synthesis and inhibition of bacterial virulence factors in a lecture entitled “Mycobacterial Polyketide Virulence Factors: Biosynthesis and Inhibition.”

Phosphoryl Transfer Reactions

In a session titled “Kinases, Phosphatases and Phosphorus in Biological Reactions” and chaired by L. Mario Amzel, speakers will discuss diverse aspects of the chemistry of phosphoryl transfer reactions. Debra Dunaway-Mariano (University of New Mexico) will present results of her comprehensive work on phosphatases in a lecture entitled “Evolution of a Robust Catalytic Scaffold for Hydrolytic Cleavage of Phosphate Ester Metabolites.”

Dustin J. Maly (University of Washington, Seattle), under the title “Bivalent Inhibitors of Protein Kinases,” will present his results on the development of cell permeable small molecules that allow the activation or inactivation of specific signaling enzymes in living cells, in particular, enzymes that mediate intracellular phosphorylation (the protein kinases and phosphatases).

Detailed aspects of the mechanism of phosphoryl transfer reactions will be presented by J. Andrew McCammon (Investigator, Howard Hughes Medical Institute, University of California, San Diego) who has used molecular dynamics simulations as well as QM/MM computational methods to study kinases and other enzymes. His lecture is titled “Computational Studies of Protein Kinases.”

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