Science, Publications, and News.

Scientific Highlights

Structural Insights into Mechanisms of Catalysis and Inhibition in Norwalk Virus Polymerase

Outbreaks of Norwalk virus are notorious for causing severe dehydration due to vomiting and diarrhea. The currently untreatable bug belongs to a superfamily of viruses that stores their genetic code as RNA. Researchers at the University of Calgary used high-resolution data from the CMCF1 beamline to determine the structure the Norwalk virus polymerase in various complexed states. The information is crucial to better understand viral replication and for drug development.

Additional details: Original publication / CLS science highlights

J. Biol. Chem., Vol. 283, Issue 12, 7705-7712, March 21, 2008

Structure–Activity Relationships of C6-Uridine Derivatives Targeting Plasmodia Orotidine Monophosphate Decarboxylase

Malaria, caused by Plasmodia parasites, has re-emerged as a major problem, imposing its fatal effects on human health, especially due to multidrug resistance. In Plasmodia, orotidine 5’-monophosphate decarboxylase (ODCase) is an essential enzyme for the de novo synthesis of uridine 5’-monophosphate. Impairing ODCase in these pathogens is a promising strategy to develop novel classes of therapeutics. Researchers from the group of Dr. E. Pai (University of Toronto) used data from the CMCF1 beamline to investigate the structure–activity relationships of various novel inhibitors of ODCase.

Additional details: Original publication

J. Med. Chem., 51 (3), 439–448, 2008. 10.1021/jm7010673

Structural Basis for the Regulation of N-Acetylglutamate Kinase by PII in Arabidopsis thaliana

PII is a highly conserved regulatory protein found in organisms across the three domains of life. PII is now known to play roles in the regulation of gene transcription, enzyme activity, and membrane channel function. In cyanobacteria and plants, PII relieves the feedback inhibition of the rate-limiting step in arginine biosynthesis catalyzed by N-acetylglutamate kinase (NAGK). Reserachers from the University of Calgary used data from the CMCF1 beamline to understand the molecular structural basis of enzyme regulation by PII.

Additional details: Original publication

J. Biol. Chem., Vol. 282, Issue 49, 35733-35740, December 7, 2007

Beamline Updates

Summer 2008

Xenon is a noble gas, which binds to specific sites in a biological macromolecule and can therefore be used to form heavy atom derivatives for structure determination. The Xenon Chamber is a simple yet effective device designed to pressurize loop-mounted biological macromolecular crystals in the presence of xenon gas at room temperature. Crystals mounted in loops such as the CrystalCap system are placed into the Xenon Chamber. Once sealed, the chamber is pressurized with xenon gas so that the crystal and macromolecules are equilibrated in a vapor saturated xenon atmosphere. Following depressurization of the chamber, the loop-mounted crystal is simply lifted and slid along the Xenon Chamber track and quickly lowered into a dewar for freezing in liquid nitrogen or propane.

2008 April

The first Se-edge MAD experiment was performed on the beamline. Since then several MAD experiments have been done at the Gd-edge.

Automated processing scripts based on XDS have been made available for onsite strategy determination and data processing.

The motors on the Vertical Focusing Mirror were replaced with better quality motors.

SGU and DCM calibration for the 13 - 18 keV energy range completed. Energies from 6.5 to 18 keV are now available.

For more dated updates please refer to our Achieved Updates Page.

CMCF Publications

Refereed Journals

2009

Osman, K. T.; L. Du, Y. He, Y. Luo Crystal Structure of Bacillus cerus D-alanyl Carrier Protein Ligase DltA in Complex with ATP J. Mol. Biol., doi:10.1016/j.jmb.2009.03.040

Yam, K.C.; I. D'Angelo, R. Kalscheuer, H. Zhu, J.X. Wang, V. Snieckus, H. Ly, P.J. Converse, W.R. Jacobs Jr, N. Strynadka, L.D. Eltis Studies of a ring-cleaving dioxygenase illuminate the role of cholesterol metabolism in the pathogenesis of Mycobacterium tuberculosis PLoS Pathog. 5(3):e1000344. Link

Capyk, J.K.; I. D'Angelo, N. Strynadka, L.D. Eltis Characterization of 3-ketosteroid 9alpha -hydroxylase, a Rieske oxygenase in the cholesterol degradation pathway of Mycobacterium tuberculosis J. Biol. Chem., doi:10.1074/jbc.M900719200

2008

Bello, A.M.; E. Poduch, Y. Liu, L. Wei, I. Crandall, X. Wang, C. Dyanand, K.C. Kain, E.F. Pai, L.P. Kotra  Structure-activity Relationships of C6-uridine Derivatives Targeting Plasmodia Orotidine Monophosphate Decarboxylase  J. Med. Chem., Vol. 51(3), pp. 439-448.

Van Straaten, K.E.; A. Hoffort, D.R. Palmer, D.A. Sanders  Purification, Crystallization and Preliminary X-ray Analysis of Inositol Dehydrogenase (IDH) from Bacillus subtilis  Acta Cryst. F, Vol. 64, pp. 98-101.

Zamyatkin, D.F.; J.M. Alonso, D.A. Harki, B.R. Peterson, P. Grochulski, K.K. Ng  Structural Insights into Mechanisms of Catalysis and Inhibition in Norwalk Virus Polymerase  J. Biol. Chem., Vol. 283(12), pp. 7705-7712.

2007

Duffy, A.; M. Fodje, R. Berg, P. Grochulski, Canadian Macromolecular Crystallography Facility (CMCF) 08ID-1 Status Update   Nuclear Instruments and Methods A, Vol. 582, pp. 82-88

Grochulski, P.; Are the Bending Magnet Beamlines Appropriate for Protein Crystallographers?  Synchrotron Radiation in Natural Science   Vol. 6, pp. 83-89

Grochulski, P.; M. Fodje, L. Delbaere  CMCF 08ID-1 Beamline at the Canadian Light Source  Acta Cryst.  A63, p.245 

Mizuno, Y.; G.B.G. Moorhead, K.K.-S. Ng  Structural Basis for the Regulation of N-acetylglutamate Kinase by PII in Arabidopsis thaliana  J. Biol. Chem.  Vol. 282, pp. 35733-35740   (Journal Cover)

Puttick, J.; C. Vieille, S.H. Song, M.N. Fodje, P. Grochulski, L.T.J. Delbaere Crystallization, Prelimary X-ray Diffraction and Structure Analysis of Thermotoga Maritima Mannitol Dehydrogenase Acta Cryst. Vol. F63 pp. 350-352  

2006

Grochulski, P.; I. Blomqvist, L. Delbaere Status of the Canadian Macromolecular Crystallography Facility: Design and Commissioning of the 08ID-1  Beamline at the Canadian Light Source Physics in Canada 62(5) pp.301-304  

Qian, X.; Y. He, X. Ma, M.N. Fodje, P. Grochulski, Y. Luo Calcium Stiffens Archaeal Rad51 Recombinase from Methanococcus Voltae for Homologous Recombination J. Biol. Chem. Vol. 281, No. 51 pp. 39380-39387