Meeting report

ACA 2006

Honolulu, HI, USA, July 22-26, 2006

The American Crystallographic Association held it’s annual meeting in a lovely place this year, Honolulu, Hawaii. Thanks to the exciting scientific program planned by Program Chair Judith Kelly, along with members of th eProgram Committe: Simon Billinge, Bryan Chakoumakos, Lachlan Cranswick, Aina Cohen, Chad Haynes, Charles Kissinger, Thomas Koetzle, Jeanette Krause, Paul Langan, Craig Ogata, Allen Oliver and Volker S. Urban; the hard work of Local Chairs Charlie Simmons and Karl Seff, and (probably) in some part due to the spectacular venue overlooking the Pacific, the meeting was among the largest the ACA has ever held, almost 1000 attendees. It was by far the most international of our meetings: 25% were non-US crystallographers and 10% of the abstracts were from Pacific Rim countries. Some of the highlights of the meeting, as excerpted from the Fall ACA RefleXions, follow. Regrettably the the selection is far from comprehensive, and probably not even representative. Connie Chidester

[Pinkerton, Einspahr and Fronczak]ACA Vice President Alan Pinkerton with Howard Einsphar and Frank Fronczak.
ACA Transactions are always published, and the 2006 Transactions Symposium topic was “The Future of Neutron Crystallography: Smaller Crystals, Larger (Macro) Molecule.” The first session, devoted to discussion of the present status and future prospects for neutron crystallography, was organized and reported by Tom Koetzle and Ray Teller. Facilities at the ISIS facility (UK) and the Spallation Neutron Source at J-PARC (Japan) were reviewed; both are developing instruments optimized for macromolecules: a new BIX-P1 diffractometer at J-PARC, and LMX, a Large-Molecule Diffractometer for Supramolecular Chemistry and Biological Structure, which will reside on the new cold neutron target station (TS2) that is under construction at ISIS. Facilities in the US include the Argonne Intense Pulsed Neutron Source, the Los Alamos Neutron Science Center, (the Protein Crystallography Station (PCS) at Los Alamos is currently the only instrument in the U.S. dedicated to neutron protein crystallography). The accelerator-based Oak Ridge Spallation Neutron Source in Tennessee was completed last spring, and when ramped up to full power, the SNS will provide the most intense pulsed neutron beams in the world.

[Sunset]Paul Langan and Alberto Podjarny organized the second session of the Symposium; their report emphasized how advances in instrumentation and sample preparation methods are pushing the limits of macromolecular structure determination. Wolfram Saenger’s studies of cyclodextrins showed the extrordinary power of neutrons to elucidate details of hydrogen bonding. The power of neutron diffraction for visualizing hydrogens in enzymes was obvious in the structures presented by Alberto Podjarny (aldose reductase), Gerry Bunick (xylose isomerase), and Chris Delwis (dihydrofolate reductase), These structures are some of the largest ever studied by neutron crystallography and remarkably were achieved by using crystals as small as 0.15mm. Dean Myles described the MAcromolecular Neutron DIffraction beam line, MANDI, which is planned for the next generation spallation neutron source at ORNL. New beam lines on next generation sources, in combination with deuteration support laboratories being developed at Los Alamos, Oak Ridge and Grenoble, will continue to push neutron macromolecular crystallography towards smaller samples and larger and more complex problems.

[Berman]The 2006 Martin J. Buerger Award was presented to Helen Berman by ACA President Bob Bau at the Symposium organized in her honor. The award recognized her lifetime work in the pioneering development of information services for the global research community of macromoleucular researchers. She played an influential role in the conception and early development of the Protein Data Bank and pioneered new methodologies in the creation and maintenance of the Nucleic Acid Database. Under her leadership, the Research Collaboratory for Structural Bioinformatics (RCSB) assumed responsibility for the PDB in 1999. Helen is a Board of Governors Prof. of Chem. and Chemical Biol. at Rutgers. Helen opened the session by taking the audience on a “Personal Journey Through Crystallographic Space”. The remaining speakers had all interacted with Helen at some point during her career.

[Majkrzak]The Bertran Eugene Warren Award for 2006 was presented by Bob Bau to Charles Majkrzak (Neutron Condensed Matter Science Group, National Inst. of Standards and Technology (NIST)) at a symposium organized in his honor: The Development of Neutron Reflectometry and its Applications to Magnetism, Soft Matter, and Biology. The award recognized his seminal contributions to the development of neutron reflectivity and his pioneering work in applying his methods to many challenging problems. In particular, he designed, optimized, and made creative use of supermirror polarizers, integrating them into neutron instruments that attain very low backgrounds and consequently the highest signal-to-noise ratio achieved anywhere.

[Uroporphyrinogen III synthase]Uroporphyrinogen III Synthase
New Structures: Heidi Schubert (U. of Utah) solved 6 new crystal forms of T. thermophilus Uroporphyrinogen III Synthase generating 10 independent structures; the group had previously solved the human structure; and the RIKEN Structural Genomics/Proteomics Initiative (RSGI) solved two additional structures. The 7 most different structures were superimposed in the image on the previous page. Heidi described the flexibility of uroporphyrinogen III synthase alone and in complex with product and how flexibility relates to its cyclization of a linear tetrapyrrole, a required step for making heme. The tetrapyrrole cofactors support life systems through their essential catalytic functions: Heme (oxidative metabolism and oxygen transport); Chlorophyll (photosynthesis); Siroheme (sulfite and nitrite assimilation); Cobalamin (vitamin B12 - methionine synthesis and methylmalonyl CoA synthesis) and coenzyme F430 (methane production). Their biosynthesis is complicated and requires anywhere from seven to 30 enzymatic reactions involving a variety of catalytic activities including decarboxylation, methylation, metal ion chelation and porphyrin ring oxidation. All five cofactors share their initial four synthetic steps, but at extended points in the pathways cofactor-specific branch points funnel intermediates towards their end product. David Garboczi and Steve Ginell:

[Rhodobacter sphaeroides bc1]The crystal structure of Rhodobacter Sphaeroides bc1 embedded in a modeled lipid bilayer. The surrounding membrane was computer generated; the membrane protein was placed into it, and overlapping lipids were removed. Lothar Esser
Membrane Proteins: Lothar Esser (NIH) described the 2.4 Å structure of a four-subunit bacterial bc1 complex (although no density is observed for subunit four). The asymmetric unit is very large, containing three dimers each of cytochrome b, cytochrome c1, and the iron sulphur protein. Density was observed for inhibitors, lipids, and detergent molecules. Although bacterial respiratory enzymes have proven more difficult to crystallize than their more complicated mitochondrial cousins, they offer unique views of the simplest way to establish the proton gradient necessary for ATP synthesis. Susan Buchanan

[Lun Gan figure]Figure by Lu Gan, reprinted from: Wikoff, W.R., Conway, J.F., Tang, J., Lee, K.K., Gan, L., Cheng, N., Duda, R.L., Hendrix, R.W., Steven, A.C., and Johnson, J.E. 2006. J. Struct. Biol. 153:300-6,© 2006, with permission from Elsevier.
Bio-Molecular Assemblies: below, from Jack Johnson (Scripps): A montage of four morphological forms of the bacteriophage HK97 capsid superimposed on the single crystal data (right) used to determine their structures and the solution scattering data (left) used to follow the transitions between forms. The earth is shown in the center to emphasize that bacteriophage constitute a significant fraction of the terrestrial biomass. Hiro Tsruta and Volker Urban

[E.coli 70s ribosome]The structure of intact E. coli 70S ribosome at 3.5 Å resolution. View from the solvent side of the small subunit. 16S rRNA and proteins in the small subunit are light blue and dark blue, respectively. 23S rRNA and in the large subunit are gray and magenta, respectively. Reprinted from B.S. Schuwirth, M.A. Borovinskaya, C.W. Hau, W. Zhang, A. Vila-Sanjurjo, J.M. Holton, J.H.D. Cate, Science, (2005) 310, 827-834, with permission from Science © 2005.

Complementary Methods to Macromolecular Crystallography: Alex McPherson (UC-Irvine) gave an introduction to atomic force microscopy and its use to investigate everything from crystal growth to the release of RNA from virus particles. The method provides nm resolution in the vertical direction of the scan and 2-3 nm resolution in the plane of the scan. AFM provides a detailed surface view of the objects investigated and it can be performed in solution. Quan Ho (Cornell) discussed small angle X-ray scattering (SAS) to determine molecular envelopes of macromolecules and the application of these envelopes for determining crystallographic phases. To do this the known envelope must be properly positioned and oriented in the crystal lattice. Bill Royer (U. Massachusetts) described time-resolved crystallography of hemoglobin, providing nano second time resolution and atomic spatial resolution of transitions that occur in the molecule as it loses its ligand and moves from the R to T state. The method requires a system that will repeatedly undergo the transformation in the crystal lattice and one that can be triggered by a laser. Andrew Stewart (Stony Brook U.), provided a progress report on the development of the X-ray microscope; Clare Peters-Libeu (Gladstone Inst., UCSF) presented a model for the human apolipoprotein E.DPPC obtained from crystallographic analysis of Bragg reflections and diffuse scattering as well as from SAS data; and Joshua Sakon (U. of Arkansas) described multiple methods, NMR, light scattering, size exclusion chromatography and thermal scanning calorimetry, to characterize the transition of the collagen binding domain of collagenase from the alpha to beta form. Jack Johnson (Scripps) finished the session by describing a 17Å resolution asymmetric cryoEM reconstruction of the bacteriophage P22. High resolution X-ray models of the tail spike proteins were readily fitted into the cryoEM density confirming the validity of the reconstruction. Jack Johnson and Alex McPherson

Connie Chidester

[Carter and Bricogne]Charles Carter and Gerard Bricogne at the Opening Reception.