X-Ray Crystallography

Please note that small-molecule X-ray crystallography services for the California campus are being provided by the University of California, San Diego Crystallography Facility. Fees will be paid for by Scripps Research.

See:
http://crystals.ucsd.edu/about.html

The mission of the core is to provide investigators state-of-the-art equipment and resources for crystallographic analysis of their target macromolecules and small inorganic or organic molecules. The core facility offers and operates as a full service core by performing crystallization, X-ray diffraction data collection (both in-house and synchrotron sources) processing, phasing, crystallographic refinement, model building, and visualization. The structural data obtained by the core will provide scientists with a wealth of information including but not limited to biological functions, 3D-folding, ligand binding (small molecule or protein), or mutational effect of target macromolecules.

Link for internal users.

Outside users are always welcome!

We also provide crystallography services to outside organizations. Please contact us for potential collaborations.

  • Minstrel III, an automatic plate handling and imaging system
  • RoboIncubators, which can store crystallization plates in a temperature and humidity controlled environment
  • Leica stereomicroscope and a high powered stereoscope for manual crystal photography, crystal screening, and crystal manipulation
  • Gryphon Crystallization Robot, which can set up nano liter drops in minutes
  • Bruker AXS Smart APEX CCD diffraction system with a molybdenum sealed X-ray tube for small molecule X-ray crystallography
  • Rigaku MicroMax-007 HFM X-ray generator with a VariMax HR optics and an X-Stream 2000 crystal cryo-freezing system
  • Mar345dtb image plate detector for recording X-ray diffraction patterns
  • Proteros Free Mounting System (FMS) for handling and manipulating room temperature grown crystals for diffraction optimization
  • Dedicated computers for data collection and processing
  • Crystallization Screening: For macromolecular crystallization experiments, the core facility uses commercially available 960 crystallization conditions plus various optimization reagents whose combination can make millions of different crystallization conditions.
  • Data Collection Service: Diffraction experiments will be performed at in-house X-ray facility as well as a synchrotron beam lines.
  • Structure Determination and Analysis: A complete data set collected at home or synchrotron will be processed for inorganic, organic, protein or nucleic acid structure determination, model building and crystallographic refinement.
  • Other Structural Biology Related Services: The core facility offers thorough analysis of a macromolecular structure or a group of structures for publication or grant applications. The core also provides computational experiments such as homology modeling and in silico ligand docking.
  • Long Term Collaborative Projects
  • Inhibitor Design and Optimization of Protein Kinases
  • RNA Repeat Expansion Disease
  • Receptor forAdvance Glycation Endproduct
  • Natural Product Inspired Synthesis

Selected Recent Publications

  1. Disney JC, Yildirim I, Park H, Lohman J, Guan L, Tran T, Sarkar P, Schatz GC, Disney MD. Structure of the Myotonic Dystrophy Type 2 RNA and Designed Small Molecules That Reduce Toxicity. JACS, 2014.
  2. Childs-Disney JL, Stepniak-Konieczna E, Tran T, Yildirim I, Park H, Chen CZ, Hoskins J, Southall N, Marugan JJ, Patnaik S, Zheng W, Austin C, George C. Schatz G, Sobczak K, Thornton CA, Disney MD. Induction and Reversal of Myotonic Dystrophy Type 1 Pre-mRNA Splicing Defects by Small Molecules. Nature Communications, 2013, Jun 28;4:2044.
  3. Feng Y, Chambers JW, Iqbal S, Koenig M, Park H, Cherry L, Hernandez P, Figuera-Losada M, LoGrasso PV. A Small Molecule Bidentate-Binding Dual Inhibitor Probe of the LRRK2 and JNK Kinases. ACS Chem Biol., 2013, Jun 10;8(8):1747-54.
  4. Yin Y, Lin L, Ruiz C, Khan S, Cameron MD, Grant W, Pocas J, Eid N, Park H, Schroeter T, LoGrasso PV, Feng Y. Synthesis and Biological Evaluation of Urea Derivatives as Highly Potent and Selective Rho Kinase (ROCK) Inhibitors. J Med Chem., 2013, Apr 9;56(9):3568-81.
  5. Jeso, V, Iqbal S, Hernandez P, Cameron MD, Park H, LoGrasso PV, Micalizio GC. Synthesis of benzoquinone ansamycin-inspired macrocyclic lactams from shikimic acid. Angewandte Chemie International Edition, 2013, Apr 26;52(18):4800-4.
  6. Yildirim I,Park H, Disney MD, Schatz GE. A Dynamic Structural Model of Expanded RNA CAG Repeats: A Refined X-ray Structure and Computational Investigations Using Molecular Dynamics and Umbrella Sampling Simulations. JACS, 2013, Mar 6, 135(9):3528-38.
  7. Zhang T, Inesta-Vaquera F, Niepel M, Zhang J, Ficarro SB, Machleidt T, Xie T, Marto JA, Kim N, Sim T, Laughlin JD, Park H, LoGrasso PV, Patricelli M, Nomanbhoy TK, Sorger PK, Alessi Dr, Gray NS. Discovery of Potent and Selective Covalent Inhibitors of JNK. Chem & Biol,2012, Jan 27;19(1):140-54.
  8. Kumar A, Park H, Fang P, Parkesh R, Guo M, Nettles KW, Disney MD. Myotonic Dystrophy Type 1 RNA Crystal Structures Reveal Heterogeneous 1 x 1 Nucleotide UU Internal Loop Conformations. Biochemistry,2011, Oct 11;50(45):9928-35.
  9. Park H, Lee JH, Gouin E, Cossart P, Izard T. The Rickettsia surface cell antigen 4 applies mimicry to bind to and activate vinculin. J Biol Chem., 2011, Jul 1;286(40):35096-103.
  10. Kumar A, Fang P, Park H, Guo M, Nettles KW, Disney MD. A Crystal Structure of a Model of the Repeating r(CGG) Transcript Found in Fragile X Syndrome. ChemBiochem,2011, 12:2140-42.
  11. Lee JH, AN JY, Park H, Kim HJ, Eom SH. Crystallization and preliminary X-ray crystallographic analysis of the human kindling-2 PH domain. Acta Cryst F,2011, 67(Pt 6):696-9
  12. Park H, Valencia-Gallardo C, Nhieu G, Izard T. Novel vinculin binding site of the IpaA invasin of Shigella. J Biol Chem., 2011, Jul 1;286(26):23214-21.
  13. Lee JH*, Park H*, Park SJ, Kim HJ, Eom SH. Structural flexibility of Shank PDZ domain is important for its binding to different ligands. BBRC, 2011, Apr 1;407(1)207-212 (*shared first authorship).

Software Packages

 

Synchrotron Sites

 

Other Resources

Contact / Staff