The NE-CAT Center for Advanced Macromolecular Crystallography operates two undulator beamlines at Sector 24 of the Advanced Photon Source, Argonne National Laboratory. Our mission is to develop advanced technologies for challenging problems in structural biology. These problems come to us as Driving Biomedical Projects (DBPs), selected for their groundbreaking science. Examples include membrane channels, transporters, and receptors;cell signaling proteins;enzymes catalyzing complex cellular processes;structural biology of translation, transcription, recombination and repair;lare RNA molecules and RNA-mediated gene regulation, and large protein complexes such as nuclear pores. These projects often confront microcrystals, inhomogeneous crystals, poorly diffracting crystals, or pathologies such as multiple lattices. To address these problems we will develop technology in three interdependent areas: (1) microbeam diffraction, (2) beamline automation, and (3) low resolution structural biology. Microbeam diffraction builds on our successful microcrystal diffraction program. We will develop technology for small (2- 5 |j,m), intense and stable microbeams, for use with microcrystals and for measuring data from selected regions of inhomogeneous crystals. We will also work out how to improve sample stability, which often limits data quality. For inhomogeneous samples we will develop optimal data-collection protocols. Beamline automation will focus on new, rapid screening protocols, automated procedures to determine the best data collection strategies, especially for multiple crystals and flexible kappa geometry, and methods for automated data processing and analysis. Low resolution structural biology is growing rapidly, driven by structural studies of multicomponent complexes and membrane proteins. We will develop technology to obtain the best possible signal-to-noise at the resolution limit while still measuring the lowest order reflections. We will develop protocols to optimize data-collection strategies and data processing, especially for multiple crystals. We will also develop on- site methods to improve the resolution of existing crystals. During the past five years we have maintained a very productive collaboration and service program. We expect the number of users (including DBPs) to remain constant at about 1000 per year. We will make our new technology available to all users as early as possible. A strength of our Center is user training. We will continue our extensive training program, while developing new approaches to train remote access users. We will continue dissemination of both technology and scientific results through mechanisms that include our web site, presentations at meetings, workshops, publications, and one-on-one contacts.

Public Health Relevance

The purpose of the proposed Center 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, these structures allow us to better understand basic biological systems often resulting in the identification of new pharmaceutical targets.

National Institute of Health (NIH)
National Institute of General Medical Sciences (NIGMS)
Biotechnology Resource Grants (P41)
Project #
Application #
Study Section
Special Emphasis Panel (ZRG1-BCMB-P (40))
Program Officer
Wu, Mary Ann
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Cornell University
Schools of Arts and Sciences
United States
Zip Code
Poor, Catherine B; Andorfer, Mary C; Lewis, Jared C (2014) Improving the stability and catalyst lifetime of the halogenase RebH by directed evolution. Chembiochem 15:1286-9
Gao, Ang; Serganov, Alexander (2014) Structural insights into recognition of c-di-AMP by the ydaO riboswitch. Nat Chem Biol 10:787-92
Sanches, Mario; Duffy, Nicole M; Talukdar, Manisha et al. (2014) Structure and mechanism of action of the hydroxy-aryl-aldehyde class of IRE1 endoribonuclease inhibitors. Nat Commun 5:4202
Sasaki, Eita; Zhang, Xuan; Sun, He G et al. (2014) Co-opting sulphur-carrier proteins from primary metabolic pathways for 2-thiosugar biosynthesis. Nature 510:427-31
Bolla, Jani Reddy; Su, Chih-Chia; Do, Sylvia V et al. (2014) Crystal structure of the Neisseria gonorrhoeae MtrD inner membrane multidrug efflux pump. PLoS One 9:e97903
Strunk, Robert J; Piemonte, Katrina M; Petersen, Natasha M et al. (2014) Structure determination of BA0150, a putative polysaccharide deacetylase from Bacillus anthracis. Acta Crystallogr F Struct Biol Commun 70:156-9
Brown, Nicholas G; Watson, Edmond R; Weissmann, Florian et al. (2014) Mechanism of polyubiquitination by human anaphase-promoting complex: RING repurposing for ubiquitin chain assembly. Mol Cell 56:246-60
Sui, Xuewu; Kiser, Philip D; Che, Tao et al. (2014) Analysis of carotenoid isomerase activity in a prototypical carotenoid cleavage enzyme, apocarotenoid oxygenase (ACO). J Biol Chem 289:12286-99
Xu, Kai; Wu, Zhuhao; Renier, Nicolas et al. (2014) Neural migration. Structures of netrin-1 bound to two receptors provide insight into its axon guidance mechanism. Science 344:1275-9
Lee, Kwangkook; Zhong, Xiaofen; Gu, Shenyan et al. (2014) Molecular basis for disruption of E-cadherin adhesion by botulinum neurotoxin A complex. Science 344:1405-10

Showing the most recent 10 out of 87 publications