Abstract

The major objective of this Core is to supply the various Projects and Cores with a continuous supply of highly purified protein in amounts necessary to complete the individual specific aims for each Project and Core, and therefore the long-term objectives of the overall Program Project.
The specific aims are to (1) collaborate with Projects 1 &2 in the cloning of SCLpro and PLpro into over-expression vectors, and to then determine their optimum expression conditions for each enzyme;(2) develop rapid and efficient purification procedures for SCLpro and PLpro enzyme constructs and determine the optimum conditions for their stabilization and storage;and (3) produce large amounts of highly purified enzyme that will be utilized by Projects 1-3, and by computational Core. The ultimate goal is to provide Projects 1-3, and the computational Core with a continuous supply of protein for the purposes of biochemical, kinetic, and biophysical characterization, x-ray structure elucidation, and high-throughput enzymatic and ligand-binding and bioassays.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Program Projects (P01)
Project #
5P01AI060915-05
Application #
7822922
Study Section
Special Emphasis Panel (ZAI1)
Project Start
Project End
Budget Start
2009-05-01
Budget End
2010-04-30
Support Year
5
Fiscal Year
2009
Total Cost
$177,416
Indirect Cost

  Institution

Name
University of Illinois at Chicago
Department
Type
DUNS #
098987217
City
Chicago
State
IL
Country
United States
Zip Code
60612

  Publications

Ghosh, Arun K; Reddy, Bhavanam Sekhara; Yen, Yu-Chen et al. (2016) Design of Potent and Highly Selective Inhibitors for Human ?-Secretase 2 (Memapsin 1), a Target for Type 2 Diabetes. Chem Sci 7:3117-3122
Báez-Santos, Yahira M; St John, Sarah E; Mesecar, Andrew D (2015) The SARS-coronavirus papain-like protease: structure, function and inhibition by designed antiviral compounds. Antiviral Res 115:21-38
Ratia, Kiira; Kilianski, Andrew; Baez-Santos, Yahira M et al. (2014) Structural Basis for the Ubiquitin-Linkage Specificity and deISGylating activity of SARS-CoV papain-like protease. PLoS Pathog 10:e1004113
Lee, Hyun; Mittal, Anuradha; Patel, Kavankumar et al. (2014) Identification of novel drug scaffolds for inhibition of SARS-CoV 3-Chymotrypsin-like protease using virtual and high-throughput screenings. Bioorg Med Chem 22:167-77
Jacobs, Jon; Grum-Tokars, Valerie; Zhou, Ya et al. (2013) Discovery, synthesis, and structure-based optimization of a series of N-(tert-butyl)-2-(N-arylamido)-2-(pyridin-3-yl) acetamides (ML188) as potent noncovalent small molecule inhibitors of the severe acute respiratory syndrome coronavirus (SARS-CoV) 3CL pr J Med Chem 56:534-46
Turlington, Mark; Chun, Aspen; Tomar, Sakshi et al. (2013) Discovery of N-(benzo[1,2,3]triazol-1-yl)-N-(benzyl)acetamido)phenyl) carboxamides as severe acute respiratory syndrome coronavirus (SARS-CoV) 3CLpro inhibitors: identification of ML300 and noncovalent nanomolar inhibitors with an induced-fit binding. Bioorg Med Chem Lett 23:6172-7
Lee, Hyun; Torres, Jaime; Truong, Lena et al. (2012) Reducing agents affect inhibitory activities of compounds: results from multiple drug targets. Anal Biochem 423:46-53
Sun, Li; Xing, Yaling; Chen, Xiaojuan et al. (2012) Coronavirus papain-like proteases negatively regulate antiviral innate immune response through disruption of STING-mediated signaling. PLoS One 7:e30802
Chaudhuri, Rima; Tang, Sishi; Zhao, Guijun et al. (2011) Comparison of SARS and NL63 papain-like protease binding sites and binding site dynamics: inhibitor design implications. J Mol Biol 414:272-88
Züst, Roland; Cervantes-Barragan, Luisa; Habjan, Matthias et al. (2011) Ribose 2'-O-methylation provides a molecular signature for the distinction of self and non-self mRNA dependent on the RNA sensor Mda5. Nat Immunol 12:137-43

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