Seattle Structural Genomics Center for Infectious Diseases --Year V
EMSL Project ID
45802
Abstract
The Seattle Structural Genomics Center for Infectious Disease (SSGCID) is funded by the National Institute of Allergy and Infectious Diseases (NIAID) to apply genome-scale approaches in solving protein structures from biodefense organisms, those causing emerging and re-emerging disease, and those showing multi-drug resistance to antimicrobial agents. The SSGCID target selection strategy has focused on drug targets, essential enzymes, virulence factors and vaccine candidates from a number of eukaryotic pathogens (Babesia, Coccidioides, Cryptosporidium, Cyclospora, Encephalitozoon, Entamoeba, Giardia, Leishmania, Plasmodium, Toxoplasma, and Trypanosoma), several bacterial genera, as well as ssDNA and negative-strand ssRNA viruses. Since the project's inception in late 2007, over 4000 targets have been selected for entry into the SSGCID structure determination pipeline, with >1000 proteins being purified for crystallization trials. SSGCID has submitted nearly 400 protein structures to the Protein Data Bank (PDB), with >50 from eukaryotic pathogens. Community input (in the form of target requests for entry into the structure determination pipeline) is actively solicited at http://ssgcid.org. All expression clones, purified proteins, and protein structures produced by SSGCID are available to the scientific community and should lay the groundwork for future research and drug discovery. While X-ray diffraction methods are the primary means of structure solution by SSGCID, some proteins fail to crystallize or produce poorly diffracting crystals. In these cases NMR-based methods are used to rescue a structure solution. SSGCID has two groups dedicated to solving structures using NMR-based methods that are lead by Drs. Gabriel Varaini (University of Washington) and Garry W. Buchko (PNNL). Each group has the goal of rescuing the structure solution of three targets per year. The suite of NMR spectrometers at EMSL has been essential for the acquisition of the data to fulfill PNNL's obligations. In the past year alone the facilities at EMSL have resulted in the deposition of three solution structures plus three XRD structures into the Protein Data Bank and the publication of nine peer-reviewed manuscripts. This EMSL proposal is a request primarily for NMR spectrometer resources to allow PNNL to fulfill their contractual obligations to NIAID in FY12 - the deposition of three additional NMR structures into the RSCB PDB. X-ray diffraction methods are the primary means of structure solution by SSGCID. However, in instances where proteins fail to crystallize or produce poorly diffracting crystals, NMR-based methods are used to rescue a structure solution. SSGCID has two groups dedicated to solving structures using NMR-based methods that are lead by Drs. Gabriel Varaini (University of Washington) and Garry W. Buchko (PNNL). Each group has the goal of rescuing the structure solution of three targets per year. The suite of NMR spectrometers at EMSL has been essential for the acquisition of the data to fulfill these obligations at PNNL. As illustrated in the appendix, the facilities at EMSL have resulted in the deposition of three solution structures plus three XRD structures into the Protein Data Bank in the last year alone. Furthermore, nine peer-reviewed manuscripts have been published, or accepted for publication in the last year alone. This EMSL proposal is a request primarily for NMR spectrometer resources to allow PNNL to fulfill their contractual obligations to NIAID in FY12, the deposition of three additional NMR structures into the RSCB PDB.
Project Details
Project type
Exploratory Research
Start Date
2011-08-29
End Date
2012-09-02
Status
Closed
Released Data Link
Team
Principal Investigator
Related Publications
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, MC Clifton, E Wallace, KA Atkins, and PJ Myler. 2017. "Backbone chemical shift assignments and secondary structure analysis of the U1 protein from the Bas-Congo virus." Biomolecular NMR Assignments 11(1):51-56. doi:10.1007/s12104-016-9719-2
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]
Elnaas A.R., D. Grice, J. Han, Y. Feng, A. Di Capau, T. Mak, and J.A. Laureanti, et al. 2020. "Discovery of a Natural Product that Binds to the Mycobacterium tuberculosis Protein Rv1466 by Native Mass Spectrometry." Molecules 25, no. 10:2384. PNNL-SA-152797. doi:10.3390/molecules25102384
Jin H, Y Zhang, GW Buchko, SM Varnum, H Robinson, TC Squier, and PE Long. 2012. "Structure Determination and Functional Analysis of a Chromate Reductase from Gluconacetobacter hansenii." PLoS One 7(8):Article No. e42432. doi:10.1371/journal.pone.0042432
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 .
Xie Y., Y. Feng, A. Di Capua, T. Mak, G.W. Buchko, P.J. Myler, and M. Lui, et al. 2020. "A Phenotarget Approach for Identifying an Alkaloid Interacting with the Tuberculosis Protein Rv1466." Marine Drugs 18, no. 3:149. PNNL-SA-150251. doi:10.3390/md18030149
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