The Northeastern Collaborative Access Team (NE-CAT) operates two undulator beamlines for macromolecular crystallography at Sector 24 of the Advanced Photon Source (APS). Beamline 24-ID-C is equipped with a Dectris PILATUS 6MF pixel array detector (PAD) and beamline 24-ID-E is equipped with an ADSC Q315 CCD-based detector. NE-CAT has operated for 15 years and is currently oversubscribed. More than 85% of the beam time is allocated to NIH funded research projects. During the past 12 months, over 160 publications resulted from data collected at NE-CAT. PADs became commercially available less than five years ago and are now established as the best available solution for collecting macromolecular crystallography data at synchrotron beamlines. Our PILATUS 6MF was commissioned about three years ago and its availability has revolutionized data collection at NE-CAT. Compared to CCD-based detectors, PADs have no readout noise, higher dynamic range, and much higher readout speed. These features allow shutterless data collection and diffractive alignment of small crystals embedded in opaque cryomedia, and result in improved data quality and resolution. Consequently, we are able to accommodate more users with a commensurate increase in productivity. The number of publications from beamline 24-ID-C in 2014 increased by more than 20% compared to the number of publications in 2013. Our experience with the PILATUS 6MF, the aging of our ADSC Q315 CCD detector, which is no longer supported, an upgrade of our 24-ID-E X-ray optics to produce intense 5 m diameter X-ray beams at the sample, and the planned APS lattice upgrade, has led us to request funding for the generation PAD, the Dectris EIGER 16M. The EIGER 16M will be installed at the NE-CAT beamline 24-ID-E as a replacement for the Q315. All of the necessary infrastructure is in place including a 384 Xeon core compute cluster and 432 TB of disk storage. The EIGER 16M has smaller pixels (75 m compared to 150 m for the PILATUS 6MF) and a faster framing rate. The EIGER 16M provides all of the advantages of the PILATUS 6MF and more. In particular, the EIGER 16M is better suited for microbeam crystallography, which is one of our major areas of emphasis. These advantages will allow us to develop serial microcystallography in which very intense beams are used to collect one or a few frames from microcrystals. The frames are then processed and merged to create a complete dataset. In the long term, the secondary KB focusing system currently being installed at 24-ID-E in combination with the APS multi-bend achromat lattice upgrade will provide about two orders increase in beam brilliance. This is ideally matched to our future plans for our microbeam crystallography program. The EIGER 16M will further enhance our technological capabilities for a broad range of projects, many of which require the unprecedented characteristics of the EIGER 16M.

Public Health Relevance

The purpose of the proposed instrument is to enhance our ability to visualize the three-dimensional structures of biological macromolecules. Many of the molecules are targets for drug design and understanding their structures will aid in the development of new pharmaceutical agents. In addition, molecular structures allow us to better understand basic biological systems often resulting in the identification of new pharmaceutical targets.

Agency
National Institute of Health (NIH)
Institute
Office of The Director, National Institutes of Health (OD)
Type
Biomedical Research Support Shared Instrumentation Grants (S10)
Project #
1S10OD021527-01
Application #
9074913
Study Section
Special Emphasis Panel (ZRG1)
Program Officer
Levy, Abraham
Project Start
2016-04-01
Project End
2017-03-31
Budget Start
2016-04-01
Budget End
2017-03-31
Support Year
1
Fiscal Year
2016
Total Cost
Indirect Cost
Name
Cornell University
Department
Chemistry
Type
Schools of Arts and Sciences
DUNS #
872612445
City
Ithaca
State
NY
Country
United States
Zip Code
14850
Bohl, Thomas E; Ieong, Pek; Lee, John K et al. (2018) The substrate-binding cap of the UDP-diacylglucosamine pyrophosphatase LpxH is highly flexible, enabling facile substrate binding and product release. J Biol Chem 293:7969-7981
Iglesias, Nahid; Currie, Mark A; Jih, Gloria et al. (2018) Automethylation-induced conformational switch in Clr4 (Suv39h) maintains epigenetic stability. Nature 560:504-508
Miller, Bradley R; Kung, Yan (2018) Structural Features and Domain Movements Controlling Substrate Binding and Cofactor Specificity in Class II HMG-CoA Reductase. Biochemistry 57:654-662
Pourfarjam, Yasin; Ventura, Jessica; Kurinov, Igor et al. (2018) Structure of human ADP-ribosyl-acceptor hydrolase 3 bound to ADP-ribose reveals a conformational switch that enables specific substrate recognition. J Biol Chem 293:12350-12359
Schaefer, Kaitlin; Owens, Tristan W; Kahne, Daniel et al. (2018) Substrate Preferences Establish the Order of Cell Wall Assembly in Staphylococcus aureus. J Am Chem Soc 140:2442-2445
Goodman, Michael C; Xu, Shu; Rouzer, Carol A et al. (2018) Dual cyclooxygenase-fatty acid amide hydrolase inhibitor exploits novel binding interactions in the cyclooxygenase active site. J Biol Chem 293:3028-3038
Pantel, Lucile; Florin, Tanja; Dobosz-Bartoszek, Malgorzata et al. (2018) Odilorhabdins, Antibacterial Agents that Cause Miscoding by Binding at a New Ribosomal Site. Mol Cell 70:83-94.e7
Omattage, Natalie S; Deng, Zengqin; Pinkner, Jerome S et al. (2018) Structural basis for usher activation and intramolecular subunit transfer in P pilus biogenesis in Escherichia coli. Nat Microbiol 3:1362-1368
Tereshchenkov, Andrey G; Dobosz-Bartoszek, Malgorzata; Osterman, Ilya A et al. (2018) Binding and Action of Amino Acid Analogs of Chloramphenicol upon the Bacterial Ribosome. J Mol Biol 430:842-852
Guenther, Elizabeth L; Cao, Qin; Trinh, Hamilton et al. (2018) Atomic structures of TDP-43 LCD segments and insights into reversible or pathogenic aggregation. Nat Struct Mol Biol 25:463-471

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