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Enzymes, Coenzymes and Metabolic Pathways

Gordon Research Conference

Enzyme Mechanisms with Applications to Metabolism, Epitranscriptomics and Drug Discovery

July 24 - 29, 2022

Chairs Andrew S. Murkin and Lynn M. Abell

Vice Chairs Satish K. Nair and Luiz Pedro Carvalho

Waterville Valley

56 Packard's Road

Waterville Valley, New Hampshire, United States

Venue and Travel Information

Conference Description

The study of enzymes, co-enzymes and metabolic pathways has defined our understanding of cellular biochemistry, enabled discovery of new therapeutic agents and even allowed the generation of new materials. In the early days, the principles of enzymology were established using relatively simple systems. As our biomolecular toolset has continued to improve, these basic concepts have enabled us to study more complex systems, providing a much deeper understanding of how enzymes function in multiple contexts. In recognition of these advances, the 2022 Gordon Research Conference on Enzymes, Coenzymes and Metabolic Pathways will embrace the fundamentals, including enzyme mechanism, inhibition and metabolism, while exploring new horizons, such as enzymes that use double-stranded RNA as substrates, enzyme structural advances and kinetics in cells or on the single-molecule level.

Related Meeting

This GRC will be held in conjunction with the "Enzymes, Coenzymes and Metabolic Pathways" Gordon Research Seminar (GRS). Those interested in attending both meetings must submit an application for the GRS in addition to an application for the GRC. Refer to the associated GRS program page for more information.

Conference Program

Sunday
2:00 pm - 9:00 pm	Arrival and Check-in
6:00 pm - 7:00 pm	Dinner
7:30 pm - 7:40 pm	Introductory Comments by GRC Site Staff / Welcome from the GRC Chair
7:40 pm - 9:30 pm	Enzymology in the Innate Immune System Discussion Leader: Heather Hundley (Indiana University, United States)
7:40 pm - 8:10 pm	Shane Buker (Accent Therapeutics, United States) "RNA Modifying Protein (RMP) Targeted Cancer Drug Discovery"
8:10 pm - 8:15 pm	Discussion
8:15 pm - 8:45 pm	Yorgo Modis (University of Cambridge, United Kingdom) "How Do Cells Sense Viral RNA? Role of ATP-dependent RNA Recognition by MDA5"
8:45 pm - 8:50 pm	Discussion
8:50 pm - 9:20 pm	Manal Swairjo (San Diego State University, United States) "Deciphering the Complex Mechanisms of tRNA Modification"
9:20 pm - 9:30 pm	Discussion
Monday
7:30 am - 8:30 am	Breakfast
9:00 am - 12:30 pm	Enzyme Evolution and Engineering Discussion Leader: Nicholas Silvaggi (University of Wisconsin-Milwaukee, United States)
9:00 am - 9:30 am	Tobias Erb (Max Planck Society, Germany) "Borrowing from Central Metabolism to Engineer New Metabolic Pathways"
9:30 am - 9:40 am	Discussion
9:40 am - 10:10 am	Donald Hilvert (ETH Zurich, Switzerland) "Design and Evolution of Artificial Enzymes"
10:10 am - 10:20 am	Discussion
10:20 am - 10:50 am	Group Photo / Coffee Break
10:50 am - 11:20 am	Paola Laurino (Okinawa Institute of Science and Technology Graduate University, Japan) "InDels: Hopeful Monsters for Protein Engineering?"
11:20 am - 11:30 am	Discussion
11:30 am - 12:00 pm	David Sherman (University of Michigan, United States) "Natural Product Discovery by Enzyme Engineering"
12:00 pm - 12:10 pm	Discussion
12:10 pm - 12:25 pm	Yang Hai (University of California Santa Barbara, United States) "Discovery of a PLP-dependent Mannich Cyclase"
12:25 pm - 12:30 pm	Discussion
12:30 pm - 1:30 pm	Lunch
1:30 pm - 4:00 pm	Free Time
3:00 pm - 4:00 pm	The GRC Power Hour™ The GRC Power Hour™ is designed to address diversity and inclusion in the scientific workplace by providing a safe environment for informal and meaningful conversations amongst colleagues of all career stages. The program supports the professional growth of all members of our communities, including ethnicity, race and/or gender identity by providing an open forum for discussion and mentoring. Organizer: Lynn Abell ( , United States)
4:00 pm - 6:00 pm	Poster Session
6:00 pm - 7:00 pm	Dinner
7:30 pm - 9:30 pm	Enzymes Involved in Post-Translational Modifications Discussion Leader: Walter Fast (University of Texas, Austin, United States)
7:30 pm - 8:00 pm	Sonja Lorenz (Max Planck Institute for Multidisciplinary Sciences, Germany) "Structural Principles of Regulation of the Ubiquitination Machinery"
8:00 pm - 8:10 pm	Discussion
8:10 pm - 8:40 pm	Minkui Luo (Memorial Sloan Kettering Cancer Center, United States) "Ligand Engagement and Transition States in Dynamic Conformational Landscapes of Protein Methyltransferases"
8:40 pm - 8:50 pm	Discussion
8:50 pm - 9:20 pm	Paul Thompson (University of Massachusetts Medical School, United States) "Chemical Approaches to Study Protein Citrullination"
9:20 pm - 9:30 pm	Discussion
Tuesday
7:30 am - 8:30 am	Breakfast
9:00 am - 12:30 pm	Inhibitor Design Discussion Leader: Lynn Abell ( , United States)
9:00 am - 9:30 am	Argyrides Argyrou (AstraZeneca, United Kingdom) "Enabling Lead Discovery of Human Methionine Adenosyltransferase"
9:30 am - 9:40 am	Discussion
9:40 am - 10:10 am	Caren Freel Meyers (Johns Hopkins University School of Medicine, United States) "Targeting a Branch Point in Bacterial Metabolism Through Inhibition of DXP Synthase"
10:10 am - 10:20 am	Discussion
10:20 am - 10:50 am	Coffee Break
10:50 am - 11:05 am	Chang Cui (Harvard University, United States) "A Putative Water Network Facilitates the Proton Transfer at the Subunit Interface of Ribonucleotide Reductase"
11:05 am - 11:10 am	Discussion
11:10 am - 11:40 am	Stephen Noell (Pfizer, United States) "Discovery of Orally Bioavailable Inhibitors of the SARS-CoV-2 Main Protease for the Treatment of COVID-19"
11:40 am - 11:50 am	Discussion
11:50 am - 12:05 pm	Yue Hao (Amgen Inc., United States) "Structures and Mechanism of Human Glycosyltransferase ß-1,3-N-acetylglucosaminyltransferase 2 (B3GNT2)"
12:05 pm - 12:10 pm	Discussion
12:10 pm - 12:25 pm	Wei-chen Chang (North Carolina State University, United States) "Non-heme Iron Enzymes Enable Structural Complexity and Diversity in Natural Products Through Oxidative C-C Bond Forming Reactions"
12:25 pm - 12:30 pm	Discussion
12:30 pm - 1:30 pm	Lunch
1:30 pm - 4:00 pm	Free Time
4:00 pm - 6:00 pm	Poster Session
6:00 pm - 7:00 pm	Dinner
7:30 pm - 9:30 pm	Conformational Effects on Catalysis and Inhibition Discussion Leader: Patrick Frantom (The University of Alabama, United States)
7:30 pm - 8:00 pm	James Fraser (University of California, San Francisco, United States) "Seeing Inhibitors and Catalytic Mechanisms with Neutron Crystallography of SARS CoV 2 Macrodomain"
8:00 pm - 8:10 pm	Discussion
8:10 pm - 8:40 pm	Kaitlin Hulce (University of Washington, United States) "Exploiting Conformational Dynamics to Inhibit Human Herpesvirus Proteases"
8:40 pm - 8:50 pm	Discussion
8:50 pm - 9:20 pm	John Richard (University at Buffalo, SUNY, United States) "The Enabling Role of Ligand-Driven Conformational Changes in Enzyme Evolution"
9:20 pm - 9:30 pm	Discussion
Wednesday
7:30 am - 8:30 am	Breakfast
9:00 am - 12:30 pm	Enzyme Kinetics in Complex Systems Discussion Leader: Dhara Shah (Arizona State University, United States)
9:00 am - 9:30 am	Swati Nagar (Temple University, United States) "A Numerical Approach to Model Cytochrome P450 Time-Dependent Inactivation"
9:30 am - 9:40 am	Discussion
9:40 am - 10:10 am	Matthew Robers (Promega, United States) "Real-time Analysis of Target Engagement Reveals Novel Vulnerabilities in the RAS-RAF Signalosome"
10:10 am - 10:20 am	Discussion
10:20 am - 10:50 am	Coffee Break
10:50 am - 11:20 am	Bharath Srinivasan (AstraZeneca PLC, United Kingdom) "In-cellulo Kinetics for the Characterization of Reversible and Irreversible Inhibitors in Early Drug Discovery"
11:20 am - 11:30 am	Discussion
11:30 am - 12:00 pm	Peter Tonge (Stony Brook University, United States) "Widening the Therapeutic Window: Kinetic Selectivity and Target Vulnerability"
12:00 pm - 12:10 pm	Discussion
12:10 pm - 12:25 pm	Jennifer Bridwell-Rabb (University of Michigan, United States) "Custom Tuning of Rieske Oxygenase Chemistry"
12:25 pm - 12:30 pm	Discussion
12:30 pm - 1:30 pm	Lunch
1:30 pm - 4:00 pm	Free Time
4:00 pm - 6:00 pm	Poster Session
6:00 pm - 7:00 pm	Dinner
7:00 pm - 7:30 pm	Business Meeting Nominations for the Next Vice Chair(s); Complete the GRC Evaluation Forms; Discuss Future Dates and Venue; Election of the Next Vice Chair(s)
7:30 pm - 9:30 pm	Enzyme Mechanisms Discussion Leader: Catherine Drennan (Massachusetts Institute of Technology, United States)
7:30 pm - 8:00 pm	Squire Booker (Pennsylvania State University, United States) "Radical Strategies for Enzymatic Methylation"
8:00 pm - 8:10 pm	Discussion
8:10 pm - 8:40 pm	Emily Parker (Victoria University of Wellington, New Zealand) "Mechanisms and Allostery in Amino Acid Biosynthesis"
8:40 pm - 8:50 pm	Discussion
8:50 pm - 9:20 pm	Timothy Wencewicz (Washington University in St. Louis, United States) "Siderophore Synthetase and Ferrichelatase Drive an Iron Shuttle in Bacteria"
9:20 pm - 9:30 pm	Discussion
Thursday
7:30 am - 8:30 am	Breakfast
9:00 am - 12:30 pm	Methodological Advances for Studying Enzymes Discussion Leader: Katherine Hicks (SUNY Cortland, United States)
9:00 am - 9:30 am	David Dulin (VU Amsterdam, The Netherlands) "The SARS-CoV-2 Replication-Transcription Complex: A Dynamic Perspective at the Single Molecule Level"
9:30 am - 9:40 am	Discussion
9:40 am - 10:10 am	Eric Greene (University of California San Francisco, United States) "CryoEM Uncovers Supramolecular Glutamine Synthetase Regulation"
10:10 am - 10:20 am	Discussion
10:20 am - 10:50 am	Coffee Break
10:50 am - 11:20 am	Denis Rousseau (Albert Einstein College of Medicine, United States) "Snapshots of Catalytic Intermediates in Cytochrome c Oxidase Using an X-ray Free Electron Laser"
11:20 am - 11:30 am	Discussion
11:30 am - 11:45 am	Nancy Horton (University of Arizona, United States) "Enzyme Filamentation/Polymerization As a Regulatory Mechanism"
11:45 am - 11:50 am	Discussion
11:50 am - 12:05 pm	Robert Jansen (Radboud University, The Netherlands) "Untargeted Metabolic Profiling of Mycobacterium Tuberculosis Identifies a new Highly Abundant Stress-Responsive Metabolite"
12:05 pm - 12:10 pm	Discussion
12:10 pm - 12:25 pm	Christopher Thibodeaux (McGill University, Canada) "Untangling the Complex Relationships between Structure and Function in Lanthipeptide Synthetases"
12:25 pm - 12:30 pm	Discussion
12:30 pm - 1:30 pm	Lunch
1:30 pm - 4:00 pm	Free Time
4:00 pm - 5:30 pm	Poster Session
5:30 pm - 7:30 pm	Keynote Session: Perspectives on Modulation of Enzyme Activity Discussion Leader: Audrey Lamb (University of Texas at San Antonio, United States)
5:30 pm - 6:20 pm	Carol Fierke (Brandeis University, United States) "Toolbox to Evaluate Biological Functions of Post-translational Modifications"
6:20 pm - 6:30 pm	Discussion
6:30 pm - 7:20 pm	Paul Fitzpatrick (University of Texas Health Science Center at San Antonio, United States) "Regulation of Aromatic Amino Acid Hydroxylation"
7:20 pm - 7:30 pm	Discussion
8:00 pm - 9:00 pm	Dinner
Friday
7:30 am - 8:30 am	Breakfast
9:00 am	Departure

Contributors

Funding for this conference was made possible [in part] by 1 R13 AI 154657 - 01 from the National Institute of Allergy and Infectious Diseases and National Center for Advancing Translational 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 of trade names, commercial practices, or organizations imply endorsement by the U.S. Government.

Conference Links

Conference History Enzymes, Coenzymes and Metabolic Pathways (GRS)

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