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Enzymes, Coenzymes & Metabolic Pathways
Discovery and Therapeutic Targeting of New Enzyme Reactions and Pathways
July 5-10, 2009
Waterville Valley Resort
Waterville Valley, NH
Chairs:
Joseph Martin Bollinger & Philip A. Cole

Vice Chairs:
Bruce A. Palfey & Thomas D. Meek

This conference highlights the fundamental questions and practical applications that motivate modern enzymology and mechanistic biochemistry. It showcases recently elucidated biological pathways and novel enzyme reactions and mechanisms. It synthesizes current thinking on the pathways by which new enzyme activities evolve and highlights cutting-edge approaches to the discovery and development of novel activities. Consistent, enthusiastic participation by industrial scientists helps to ensure that important enzyme targets for, and state-of-the-art approaches to, development of new drug therapies are brought forward. This year's meeting will include sessions on enzymes in medicine, chromatin remodeling and transcription, nucleic acid enzymology, antibiotic development, pathway discovery, phosphorylation in cell signaling, discovery and design of new activities and inhibitors, principles of enzyme catalysis, and novel reactions and mechanisms.

SUNDAY
2:00 pm - 9:00 pmArrival and Check-in (Office Closed 6:00 pm - 7:00 pm)
6:00 pmDinner
7:30 pm - 7:40 pmWelcome / Introductory Comments by GRC Site Staff
7:40 pm - 9:30 pmANTIBIOTIC DEVELOPMENT
Discussion Leader: Pinghua Liu (Boston University)
7:40 pm - 8:05 pm John Blanchard (Albert Einstein Med.)
"Defining Targets in Mycobacterium tuberculosis"
8:05 pm - 8:15 pm Discussion
8:15 pm - 8:40 pm Suzanne Walker (Harvard Med.)
"Cell Wall Biosynthesis and Its Inhibition"
8:40 pm - 8:50 pm Discussion
8:50 pm - 9:15 pm Jon Clardy (Harvard Med.)
"What we can learn from bacteria-insect mutualisms"
9:15 pm - 9:25 pm Discussion
MONDAY
7:30 am - 8:30 amBreakfast
9:00 am - 12:30 pmENZYMES IN MEDICINE
Discussion Leader: Jack Kirsch (U.C. Berkeley)
9:00 am - 9:30 am Jay Grobler (Merck Co.)
"Kinetics of integrase inhibition supports one shot kill of HIV replication"
9:30 am - 9:40 am Discussion
9:40 am - 9:55 am Fan Fan (Albert Einstein College of Medicine)
"Towards a new chemotherapy for tuberculosis: Mechanistic structural analysis of BlaC from mycobacterium tuberculosis"
9:55 am - 10:00 am Discussion
10:00 am - 10:15 am Pinghua Liu (Boston University)
"Mechanistic studies of IspH in prokaryotic isoprenoid biosynthesis"
10:15 am - 10:20 am Discussion
10:20 am Coffee Break / Group Photo
10:50 am - 11:20 am Theodore Holman (U.C. Santa Cruz)
"Kinetic, Structural and Inhibitory Studies of Human Lipoxygenase Isozymes"
11:20 am - 11:30 am Discussion
11:30 am - 12:00 pm Craig Cameron (Penn State Univ.)
"Dynamics of the viral RNA-dependent RNA polymerase: Determinant of incorporation fidelity and viral virulence and universal platform for live-virus vaccine design"
12:00 pm - 12:10 pm Discussion
12:10 pm - 12:25 pm Mark Hixon (Takeda Pharmaceuticals)
"Drug combination studies: Theory and analysis"
12:25 pm - 12:30 pm Discussion
12:30 pmLunch
1:30 pm - 4:00 pmFree Time
4:00 pm - 6:00 pmPoster Session I
6:00 pmDinner
7:30 pm - 9:30 pmNUCLEIC ACID ENZYMOLOGY
Discussion Leader: Irene Lee (Case Western Univ.)
7:30 pm - 8:00 pm Jim Stivers (Johns Hopkins Med.)
"The dynamic landscape for enzymatic recognition of DNA damage"
8:00 pm - 8:10 pm Discussion
8:10 pm - 8:40 pm Alex Drohat (Univ. Maryland)
"Thymine DNA glycosylase in base excision repair - Mechanistic insight from structure and kinetics"
8:40 pm - 8:50 pm Discussion
8:50 pm - 9:20 pm Jackie Barton (Caltech)
"DNA-mediated Signaling"
9:20 pm - 9:30 pm Discussion
TUESDAY
7:30 am - 8:30 amBreakfast
9:00 am - 12:30 pmDISCOVERY AND ELUCIDATION OF ENZYMATIC PATHWAYS
Discussion Leader: Anthony Sauve (Cornell Med.)
9:00 am - 9:30 am Charles Brenner (University of Iowa)
"Functional Interrogation of the NAD Metabolome"
9:30 am - 9:40 am Discussion
9:40 am - 10:10 am Tracey Rouault (NIH)
"Iron-sulfur proteins and human disease"
10:10 am - 10:20 am Discussion
10:20 am Coffee Break
10:50 am - 11:20 am Eric Brown (McMaster Univ., Canada)
"Probing uncharted physiology in bacteria with genetics, biochemistry and small molecules"
11:20 am - 11:30 am Discussion
11:30 am - 12:00 pm Benjamin Cravatt (Scripps)
"Characterization of enzymatic pathways by activity-based proteomics"
12:00 pm - 12:10 pm Discussion
12:10 pm - 12:25 pm Caren Meyers (Johns Hopkins Med.)
"Exploring catalytic promiscuity of 1-deoxy-D-xylulose 5-phosphate synthase"
12:25 pm - 12:30 pm Discussion
12:30 pmLunch
1:30 pm - 4:00 pmFree Time
4:00 pm - 6:00 pmPoster Session II
6:00 pmDinner
7:30 pm - 9:30 pmNOVEL REACTIONS AND MECHANISMS
Discussion Leader: Liviu Mirica (Washington Univ., St. Louis)
7:30 pm - 8:00 pm Wilfred van der Donk (Univ. Illinois, Urbana-Champaign, HHMI)
"Unusual Transformations during the Biosynthesis of Phosphonate Natural Products"
8:00 pm - 8:10 pm Discussion
8:10 pm - 8:40 pm Jennifer Dubois (Notre Dame)
"Chlorite dismutase: a heme-dependent, O2-evolving enzyme"
8:40 pm - 8:50 pm Discussion
8:50 pm - 9:20 pm Steve Rokita (Univ. Maryland)
"What's a flavoprotein doing catalyzing a reductive dehalogenation in mammals?"
9:20 pm - 9:30 pm Discussion
WEDNESDAY
7:30 am - 8:30 amBreakfast
9:00 am - 12:30 pmCHROMATIN REMODELING AND TRANSCRIPTION
Discussion Leader: Weiping Zheng (Univ. Akron)
9:00 am - 9:30 am Jerry Workman (Stowers Instit.)
"Histone modifications during transcription elongation"
9:30 am - 9:40 am Discussion
9:40 am - 10:10 am Ali Shilatifard (Stowers Instit.)
"Histone methylase enzymology learned in yeast and its implications on human leukemia"
10:10 am - 10:20 am Discussion
10:20 am Coffee Break
10:50 am - 11:20 am Paul Thompson (Univ. South Carolina)
"Chemical probes for arginine modifying enzymes"
11:20 am - 11:30 am Discussion
11:30 am - 12:00 pm Tom Muir (Rockefeller Univ.)
"Regulation of the Histone Methyltransferase Dot1 by Nucleosome Ubiquitylation"
12:00 pm - 12:10 pm Discussion
12:10 pm - 12:25 pm Patrick O'Brien (Univ of Michigan)
"The search for DNA damage by alkyladenine DNA glycosylase"
12:25 pm - 12:30 pm Discussion
12:30 pmLunch
1:30 pm - 4:00 pmFree Time
4:00 pm - 6:00 pmPoster Session III
6:00 pmDinner
7:30 pm - 9:30 pmPHOSPHORYLATION IN CELL SIGNALING
Discussion Leader: Karen Allen (Boston Univ.)
7:30 pm - 8:00 pm Louise Johnson (Oxford Univ., UK)
"Recognition properties of cyclin dependent protein kinases"
8:00 pm - 8:10 pm Discussion
8:10 pm - 8:40 pm Jin Zhang (Johns Hopkins Med.)
"Dynamic Visualization of Kinase Activity in Living Cells"
8:40 pm - 8:50 pm Discussion
8:50 pm - 9:20 pm Zhong-Yin Zhang (Indiana Univ. Med.)
"Targeting Protein Tyrosine Phosphatases for Drug Development or Chemical Genomics of Protein Tyrosine Phosphatases"
9:20 pm - 9:30 pm Discussion
THURSDAY
7:30 am - 8:30 amBreakfast
9:00 am - 12:30 pmDESIGN AND DISCOVERY OF NEW ACTIVITIES AND INHIBITORS
Discussion Leader: Garry Dotson (Univ. Michigan)
9:00 am - 9:30 am John Gerlt (Univ. Illinois, Urbana-Champaign)
"Discovering and Predicting New Functions in the Enolase and RuBisCO Superfamilies"
9:30 am - 9:40 am Discussion
9:40 am - 10:10 am Dustin Maly (Univ. Washington)
"Designing next generation protein kinase inhibitors"
10:10 am - 10:20 am Discussion
10:20 am Coffee Break
10:50 am - 11:20 am David Baker (Univ. Washington)
"Designing enzymes de novo"
11:20 am - 11:30 am Discussion
11:30 am - 11:45 am Giovanni Gadda (Georgia State Univ)
"Branching of a reaction intermediate formed during turnover of N. crassa 2-nitropropane dioxygenase inflates the observed kinetic isotope effect for the reaction"
11:45 am - 11:50 am Discussion
11:50 am - 12:05 pm Joe Barycki (Univ of Nebraska)
"Mechanistic details of glutathione biosynthesis revealed by crystal structures of S. cerevisiae glutamate cysteine ligase"
12:05 pm - 12:10 pm Discussion
12:10 pm - 12:25 pm Anne-Francis Miller (Univ of Kentucky)
"SS-NMR as a probe of flavin electronics and tuning produced by H-bonds"
12:25 pm - 12:30 pm Discussion
12:30 pmLunch
1:30 pm - 4:00 pmFree Time
4:00 pm - 6:00 pmPoster Session IV
6:00 pmDinner
7:00 pm - 7:30 pmBusiness Meeting
(Nominations for the next Vice Chair; Fill out Conference Evaluation Forms; Discuss future Site & Scheduling preferences; Election of the next Vice Chair)
7:30 pm - 9:30 pmPRINCIPLES OF ENZYME CATALYSIS
Discussion Leader: Audrey Lamb (University of Kansas)
7:30 pm - 8:00 pm John Richard (SUNY Buffalo)
"Triosephosphate isomerase and the role of flexible loops in enzymatic catalysis"
8:00 pm - 8:10 pm Discussion
8:10 pm - 8:40 pm Stephen Benkovic (Penn State University)
"A Perspective on Biological Catalysis"
8:40 pm - 8:50 pm Discussion
8:50 pm - 9:20 pm Dan Herschlag (Stanford University)
"Frontiers in Structure-Function Discovery"
9:20 pm - 9:30 pm Discussion
FRIDAY
7:30 am - 8:30 amBreakfast
9:00 amDepart
Funding for this conference was made possible in part by 5R13 GM 085811 - 02 from the National Institute of General Medical Sciences. The views expressed in written conference materials or publications and by speakers and moderators do not necessarily reflect the official policies of the Department of Health and Human Services; nor does mention by trade names, commercial practices, or organizations imply endorsement by the U.S. Government.
 
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