Seattle Structural Genomics Center for Infectious Diseases
EMSL Project ID
29292
Abstract
The Seattle Structural Genomics Center for Infectious Disease (SSGCID) is a consortium of four institutions (Seattle Biomedical Research Institue (SBRI), deCODE biostructures, University of Washington (UW), and Battelle Memorial Institute) recently funded by NIAID in response to RFP-NIH-NIAID-DMID-07-19. This center is lead by Dr. Peter Myler at SBRI, a world leader on the genomics of three related parasites that cause leishmaniasis, Chagas disease, and African sleeping sickness. SSGCIDs primary mission is to determine the structure of ~80 protein targets each year, for a period of five years, from NIAID Category A-C organisms as well as emerging and re-emerging infectious disease organisms. Of these 80 structure, the NMR group in the consotium, composed of Drs. G. Varani (University of Washington) and G.W. Buchko (PNNL) is mandated to determine six structures per year using NMR-based methods. This mission will be accomplished by employing a high-throughput gene-to-structure pipeline involving a multi-pronged serial escalation approach to protein expression in bacterial, wheat-germ cell-free translation, baculovirus and mammalian protein expression systems followed by structure determination using X-ray crystallography and NMR spectroscopy. Pro-active engagement of the infectious disease research and drug therapy communities in the target selection process will help ensure that the resulting protein structures provide a blueprint for structure-based drug design of new therapeutics to combat infectious diseases. This goal will be facilitated by the annual selection of a small number of high-impact targets for a fragment-based drug lead discovery campaign within SSGCID. The consortium is also committed to providing structural genomics service to the research community and publicly disseminating all structure information and material resources generated as part of the NIAID contract.
Project Details
Project type
Exploratory Research
Start Date
2008-03-05
End Date
2009-03-08
Status
Closed
Released Data Link
Team
Principal Investigator
Team Members
Related Publications
Recent contributions of structure-based drug design to the development of antibacterial compounds
Staker BL, GW Buchko, and PJ Myler. 2015. "Recent contributions of structure-based drug design to the development of antibacterial compounds." Current Opinion in Microbiology 27(1):133-138. doi:10.1016/j.mib.2015.09.003 .
Backbone chemical shift assignments for the sensor domain of the Burkholderia pseudomallei histidine kinase RisS: “missing” resonances at the dimer interface
Buchko GW, TE Edwards, SN Hewitt, I Phan, WC Van Voorhis, SI Miller, and PJ Myler. 2015. "Backbone chemical shift assignments for the sensor domain of the Burkholderia pseudomallei histidine kinase RisS – "missing" resonances at the dimer interface." Biomolecular NMR Assignments. doi:10.1007/s12104-015-9614-2 [In Press]
Solution-state NMR structure of the putative morphogene protein BolA (PFE0790c) fromPlasmodium falciparum
Buchko GW, A Yee, A Semesi, PJ Myler, CH Arrowsmith, and R Hui. 2015. "Solution-state NMR structure of the putative morphogene protein BolA (PFE0790c) from Plasmodium falciparum." Acta Crystallographica. Section F F71(5):514-521. doi: 10.1107/S2053230X1402799X
Structure of a CutA1 divalent-cation tolerance protein fromCryptosporidium parvum, the protozoal parasite responsible for cryptosporidiosis
Buchko GW, J Abendroth, MC Clifton, H Robinson, Y Zhang, SN Hewitt, BL Staker, TE Edwards, WC Van Voorhis, and PJ Myler. 2015. "Structure of a CutA1 divalent-cation tolerance protein from Cryptosporidium parvum, the protozoal parasite responsible for cryptosporidiosis." Acta Crystallographica. Section F F71(5):522-530. doi:10.1107/S2053230X14028210
Increasing the structural coverage of tuberculosis drug targets
Baugh L, I Phan, DW Begley, MC Clifton, B Armour, DM Dranow, BM Taylor, MM Muruthi, J Abendroth, JW Fairman, D Fox III, SH Dieterich, BL Staker, AS Gardberg, R Choi, SN Hewitt, AJ Napuli, J Myers, L Barrett, Y Zhang, M Ferrell, E Mundt, K Thompkins, N Tran, S Lyons-Abbott, A Abramov, A Sekar, D Serbzhinskiy, D Lorimer, GW Buchko, R Stacy, LJ Stewart, TE Edwards, WC Van Voorhis, and PJ Myler. 2015. "Increasing the Structural Coverage of Tuberculosis Drug Targets ." Tuberculosis 95(2):142-148. doi:10.1016/j.tube.2014.12.003
Solution structure of a putative FKBP-type peptidyl-propyl cis–trans isomerase from Giardia lamblia
Buchko GW, SN Hewitt, WC Van Voorhis, and PJ Myler. 2013. "Solution structure of a putative FKBP-type peptidyl-propyl cis-trans isomerase from Giardia lamblia." Journal of Biomolecular NMR 57(4):369-374. doi:10.1007/s10858-013-9797-8
Crystal structure of a macrophage migration inhibitory factor from Giardia lamblia
Buchko GW, J Abendroth, H Robinson, Y Zhang, SN Hewitt, TE Edwards, WC Van Voorhis, and PJ Myler. 2013. "Crystal structure of a macrophage migration inhibitory factor from Giardia lamblia." Journal of Structural and Functional Genomics 14(2):47-57. doi:10. 1007/s10969-013-9155-9
Structural insights into the functional role of the Hcn sub-domain of the receptor-binding domain of the botulinum neurotoxin mosaic serotype C/D
Zhang Y, A Gardberg, TE Edwards, B Sankaran, H Robinson, SM Varnum, and GW Buchko. 2013. "Structural Insights into the Functional Role of the Hcn Sub-domain of the Receptor-Binding Domain of the Botulinum Neurotoxin Mosaic Serotype C/D." Biochimie 95(7):1379-1385. doi:10.1016/j.biochi.2013.03.006
Combining Functional and Structural Genomics to Sample the Essential Burkholderia Structome
Baugh L, LA Gallagher, R Patrapuvich, MC Clifton, AS Gardberg, TE Edwards, B Armour, DW Begley, SH Dieterich, DM Dranow, J Abendroth, JW Fairman, D Fox III, BL Staker, I Phan, A Gillespie, R Choi, S Nakazawa-Hewitt, MT Nguyen, AJ Napuli, L Barrett, GW Buchko, R Stacy, PJ Myler, LJ Stewart, C Manoil, and WC Van Voorhis. 2013. "Combining Functional and Structural Genomics to Sample the Essential Burkholderia Structome." PLoS One 8(1):e53851. doi:10.1371/journal.pone.0053851
Chemical shift assignments for Rv0577, a putative glyoxylase associated with virulence from Mycobacterium tuberculosis
Buchko GW, H Kim, PJ Myler, TC Terwilliger, and CY Kim. 2012. "Chemical shift assignments for Rv0577, a putative glyoxylase associated with virulence from Mycobacterium tuberculosis ." Biomolecular NMR Assignments 6(1):43-46. doi:10.1007/s12104-011-9322-5
Structural Genomics-A Goldmine of Blueprints for Structure-Based Drug Design
Buchko GW. 2011. "Structural genomics - A goldmine of blueprints for structure-based drug design." Metabolomics 1(2):104e. doi:10.4172/2153-0769.1000104e