This proposal is a joint application from the Argonne National Laboratory, European Bioinformatics Institute, Northwestern University, University College London, University of Texas, University of Toronto, University of Virginia, Washington University to establish the Midwest Center for Structural Genomics (MCSG); a Large-Scale Center of the Protein Structure Initiative. The primary objective of the MCSG is to rapidly determine the structures of strategically selected bio-medically important and high-value targets including proteins from pathogens and higher eukaryotes. The goal is to elucidate protein folding space and ultimately provide structural coverage of major protein families with sufficient granularity to allow 3D homology modeling of all proteins using only computational methods. This will provide the foundation for 21st century structural biology when structures of virtually all proteins will be found in the Protein Data Bank (PDB) or derived by computational methods. MCSG will achieve these goals by implementing and refining rapid, highly integrated and cost effective methods for structure determination by x-ray crystallography at 3rd generation synchrotrons. We will continue development of advanced data management systems and databases that are vital to the primary mission. In the PSI pilot phase, the MCSG established a structure determination platform that included: (1) classifying all available genomic sequences to establish a prioritized target set, (2) cloning, and expressing genes and gene fragments of microbial and eukaryotic origin, (3) purifying and crystallizing native and derivatized protein for x-ray crystallography, (4) collecting data and determining structures, (5) analyzing structures for fold and function assignment, and homology modeling of related proteins. The platform provides for rapid model validation and deposition in PDB. In PSI-2, these steps will be further advanced and integrated using LIMs and databases into a system capable of determining 200+ structures per year at a cost of <$50K per structure. The MCSG organization is an excellent example of a highly effective and successful consortium that reflects the scale and complexity of a structural genomics production center. Our multi-institution consortium has assembled a highly integrated and interdisciplinary team prepared to enter the production phase of PSI-2. We propose to actively interact with the scientific community, contribute to the PSI Network Knowledge Base, conduct technology training and will make all methods and results developed in the course of this program readily available to the scientific community.

National Institute of Health (NIH)
National Institute of General Medical Sciences (NIGMS)
Specialized Center--Cooperative Agreements (U54)
Project #
Application #
Study Section
Special Emphasis Panel (ZGM1-CBB-3 (LC))
Program Officer
Norvell, John C
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
University of Chicago
Organized Research Units
United States
Zip Code
Sachleben, Joseph R; Adhikari, Aashish N; Gawlak, Grzegorz et al. (2017) Aromatic claw: A new fold with high aromatic content that evades structural prediction. Protein Sci 26:208-217
Rolando, Monica; Escoll, Pedro; Nora, Tamara et al. (2016) Legionella pneumophila S1P-lyase targets host sphingolipid metabolism and restrains autophagy. Proc Natl Acad Sci U S A 113:1901-6
Filippova, Ekaterina V; Kieser, Karen J; Luan, Chi-Hao et al. (2016) Crystal structures of the transpeptidase domain of the Mycobacterium tuberculosis penicillin-binding protein PonA1 reveal potential mechanisms of antibiotic resistance. FEBS J 283:2206-18
McGregor, Nicholas; Morar, Mariya; Fenger, Thomas Hauch et al. (2016) Structure-Function Analysis of a Mixed-linkage ?-Glucanase/Xyloglucanase from the Key Ruminal Bacteroidetes Prevotella bryantii B(1)4. J Biol Chem 291:1175-97
Green, Keith D; Biswas, Tapan; Chang, Changsoo et al. (2015) Biochemical and structural analysis of an Eis family aminoglycoside acetyltransferase from bacillus anthracis. Biochemistry 54:3197-206
Babnigg, György; Jedrzejczak, Robert; Nocek, Boguslaw et al. (2015) Gene selection and cloning approaches for co-expression and production of recombinant protein-protein complexes. J Struct Funct Genomics 16:113-28
Crowe, Adam M; Stogios, Peter J; Casabon, Israël et al. (2015) Structural and functional characterization of a ketosteroid transcriptional regulator of Mycobacterium tuberculosis. J Biol Chem 290:872-82
Alcaide, María; Tchigvintsev, Anatoli; Martínez-Martínez, Mónica et al. (2015) Identification and characterization of carboxyl esterases of gill chamber-associated microbiota in the deep-sea shrimp Rimicaris exoculata by using functional metagenomics. Appl Environ Microbiol 81:2125-36
Fan, Yao; Tan, Kemin; Chhor, Gekleng et al. (2015) EsxB, a secreted protein from Bacillus anthracis forms two distinct helical bundles. Protein Sci 24:1389-400
Banta, Amy B; Cuff, Marianne E; Lin, Hueylie et al. (2014) Structure of the RNA polymerase assembly factor Crl and identification of its interaction surface with sigma S. J Bacteriol 196:3279-88

Showing the most recent 10 out of 136 publications