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Seattle Structural Genomics Center for Infectious Diseases – Year VIII


EMSL Project ID
48683

Abstract

The Seattle Structural Genomics Center for Infectious Disease (http://ssgcid.org), is one of two Structural Genomics Centers (SGCs) funded by NIAID to solve protein structures from biodefense organisms and emerging infectious diseases. The SGCs actively engage with infectious disease researchers to select Community Request (CR) targets for entry in the pipeline and to collaboratively interpret and publish results from successful structure determinations. SSGCID target selection focuses on essential enzymes, virulence factors, drug targets and vaccine candidates from 8 bacterial, 12 protozoan, and 14 viral genera. Target genes are PCR amplified, cloned and screened for expression in E. coli. Soluble proteins are purified in milligram amounts, screened for crystallization, and analyzed by X-ray diffraction using an in-house source or off-site synchrotron beam-line. Small proteins that fail to crystallize are queued for structure determination by NMR. To date, over halve of the structures solved using NMR-based methods used NMR data collected at EMSL. All SSGCID expression clones, purified proteins, and structures are publicly available. The vision is that these structures will serve as starting points for structure-based drug design against infectious diseases.

Project Details

Start Date
2014-11-04
End Date
2015-09-30
Status
Closed

Team

Principal Investigator

Garry Buchko
Institution
Pacific Northwest National Laboratory

Related Publications

Structural diversity in the Mycobacteria DUF3349 superfamily

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

Solution NMR structures of oxidized and reducedEhrlichia chaffeensisthioredoxin: NMR-invisible structure owing to backbone dynamics

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

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

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

Backbone chemical shift assignments and secondary structure analysis of the U1 protein from the Bas-Congo virus

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

Accurate de novo design of hyperstable constrained peptides

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

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