SSGCID - Year VII
EMSL Project ID
48233
Abstract
Protecting the nation through innovative scientific discovery is the mission of EMSL and the mission of The Seattle Structural Genomics Center for Infectious Disease (SSGCID). The SSGCID is funded by the National Institute of Allergy and Infectious Diseases NIAID) until 2017 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 5000 targets have been selected for entry into the SSGCID structure determination pipeline, with >1300 proteins being purified for crystallization trials. SSGCID has submitted over 620 protein structures to the Protein Data Bank (PDB) over the past five years, with over 100 from eukaryotic pathogens. For several organisms (including Babesia, Coccidioides and Entamoeba), these structures represent all or most of the PDB submissions during this time. We expect to solve a further 60-80 structures over the next year of the project. 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. About one third of all SSGCID structures contain bound ligands, about half of which were obtained from fragment screening co-crystallization campaigns on several high-value targets. The vision is that these structures may serve as starting points for structure-based drug design collaborative projects.
Project Details
Start Date
2013-12-18
End Date
2014-09-30
Status
Closed
Released Data Link
Team
Principal Investigator
Related Publications
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Bhardwaj G ,Mulligan V K,Bahl C D,Gilmore J M,Harvey P ,Cheneval O ,Buchko G W,Pulavarti S V,Kass Q ,Eletsky A ,Huang PS ,Johnsen W A,Griesen P ,Rocklin G J,Song Y ,Linsky T W,Watkins A ,Rettie S A,Carter L P,Bonneau R A,Olsen J M,Coutsias E ,Correnti C E,Szyperski T ,Craik D J,Baker D 2016. "Accurate de novo design of hyperstable constrained peptides" Nature 538(7625):329-335. 10.1038/nature19791
Buchko GW, A Perkins, D Parsonage, LB Poole, and PA Karplus. 2016. "Backbone chemical shift assignments for Xanthomonas campestris peroxiredoxin Q in the reduced and oxidized states: a dramatic change in backbone dynamics." Biomolecular NMR Assignments 10(1):57-61. doi:10.1007/s12104-015-9637-8
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 G.W., J. Abendroth, J.I. Robinson, I. Phan, P.J. Myler, and T.E. Edwards. 2020. "Structural diversity in the mycobacteria DUF3349 superfamily." Protein Science 29, no. 3:670-685. PNNL-SA-147115. doi:10.1002/pro.3758
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, N Echols, EM Flynn, HL Ng, S Stephenson, H Kim, PJ Myler, TC Terwilliger, T Alber, and CY Kim. 2017. "Structural and biophysical characterization of the Mycobacterium tuberculosis protein Rv0577, a protein associated with neutral red staining of virulent tuberculosis strains and homologue of the Streptomyces coelicolor protein KbpA." Biochemistry 56(30):4015-4027. doi:10.1021/acs.biochem.7b00511
Buchko G.W., S.N. Hewitt, W.C. Van Voorhis, and P.J. Myler. 2018. "Solution NMR Structures of Oxidized and Reduced Ehrlichia chaffeensis thioredoxin: NMR-Invisible Structure Owing to Backbone Dynamics." Acta Crystallographica. Section F 74, no. 1:46-56. PNNL-SA-126464. doi:10.1107/S2053230X1701799X
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
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