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
Backbone and side chain 1H, 13C, and 15N NMR assignments for the organic hydroperoxide resistance protein (Ohr) from Burkholderia pseudomallei
Garry W. Buchko, Stephen N. Hewitt, Alberto J. Napuli, Wesley C. Van Voorhis, Peter J. Myler
Received: 28 January 2009 / Accepted: 11 May 2009 / Published online: 29 May 2009
Biomol NMR Assign (2009) 3:163–166 DOI 10.1007/s12104-009-9165-5
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
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
Buchko GW. 2011. "Structural genomics - A goldmine of blueprints for structure-based drug design." Metabolomics 1(2):104e. doi:10.4172/2153-0769.1000104e
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
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
Buchko GW, I Phan, L Cron, R Stacy, LJ Stewart, BL Staker, TE Edwards, G Varani, WC Van Voorhis, and PJ Myler. 2012. "Behind Every Good Metabolite there is a Great Enzyme (and perhaps a structure)." Metabolomics 2(6):Article No. e124.
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
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
Buchko GW, SN Hewitt, AJ Napuli, WC Van Voorhis, and PJ Myler. 2011. "Solution structure of an arsenate reductase-related protein, YffB, from Brucella melitensis, the etiological agent responsible for brucellosis." Acta Crystallographica. Section F 67(9):1129-1136. doi:10.1107/S1744309111006336
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
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 9(2):381-385. doi:10.1007/s12104-015-9614-2
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]
Myler PJ, R Stacy, LJ Stewart, BL Staker, WC Van Voorhis, G Varani, and GW Buchko. 2009. "The Seattle Structural Genomics Center for Infectious Disease (SSGCID)." Infectious Disorders Drug Targets 9(5):493-506.
Stacy R, DW Begley, I Phan, BL Staker, WC Van Voorhis, G Varani, GW Buchko, LJ Stewart, and PJ Myler. 2011. "Structural genomics of infectious disease drug targets: the SSGCID." Acta Crystallographica. Section F 67(9):979-984. doi:10.1107/S1744309111029204
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 .
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