This project comprises the final computational steps for the determination of the structures of novel crystalline bacterial proteins of unknown function identified by genomic sequencing. It relies on the data collected at the Advanced Photon source at Argonne, and precedes the functional and structural analysis steps. The project is divided into three steps: phase determination, initial model building, and model refinement. The goal is to apply current state-of-the-art computational tools to allow postdoctoral level scientists under the supervision of the PI of this proposal and her colleagues (Howard, Poljak, and Gilliland) to complete all three steps for three to four proteins per year per investigator. Reliance upon multi-wavelength anomalous diffraction (MAD) methods as the primary source of experimental phasing information, and upon the most current automated procedures of model building and refinement, is the planned approach to attain this high level of productivity. If MAD phasing cannot be used, the SIR/SAS, Mir and other methods would then be employed. Continuous assessment of progress on the various proteins under study and alteration of priorities as needed will be employed to help increase throughput.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Program Projects (P01)
Project #
5P01GM057890-02
Application #
6204322
Study Section
Project Start
1999-08-01
Project End
2000-07-31
Budget Start
1997-10-01
Budget End
1998-09-30
Support Year
2
Fiscal Year
1999
Total Cost
Indirect Cost
Name
University of MD Biotechnology Institute
Department
Type
DUNS #
City
Baltimore
State
MD
Country
United States
Zip Code
21202
Zhao, Hong; Lim, Kap; Choudry, Anthony et al. (2012) Correlation of structure and function in the human hotdog-fold enzyme hTHEM4. Biochemistry 51:6490-2
Chen, Chen; Gorlatova, Natalia; Kelman, Zvi et al. (2011) Structures of p63 DNA binding domain in complexes with half-site and with spacer-containing full response elements. Proc Natl Acad Sci U S A 108:6456-61
Lim, Kap; Pullalarevu, Sadhana; Surabian, Karen Talin et al. (2010) Structural basis for the mechanism and substrate specificity of glycocyamine kinase, a phosphagen kinase family member. Biochemistry 49:2031-41
Chen, Chen; Sun, Qihong; Narayanan, Buvaneswari et al. (2010) Structure of oxalacetate acetylhydrolase, a virulence factor of the chestnut blight fungus. J Biol Chem 285:26685-96
Melamud, Eugene; Moult, John (2009) Stochastic noise in splicing machinery. Nucleic Acids Res 37:4873-86
Melamud, Eugene; Moult, John (2009) Structural implication of splicing stochastics. Nucleic Acids Res 37:4862-72
Chao, Kinlin L; Lim, Kap; Lehmann, Christopher et al. (2008) The Escherichia coli YdcF binds S-adenosyl-L-methionine and adopts an alpha/beta-fold characteristic of nucleotide-utilizing enzymes. Proteins 72:506-9
Zhuang, Zhihao; Song, Feng; Zhao, Hong et al. (2008) Divergence of function in the hot dog fold enzyme superfamily: the bacterial thioesterase YciA. Biochemistry 47:2789-96
Willis, Mark A; Zhuang, Zhihao; Song, Feng et al. (2008) Structure of YciA from Haemophilus influenzae (HI0827), a hexameric broad specificity acyl-coenzyme A thioesterase. Biochemistry 47:2797-805
Sari, Nese; He, Yanan; Doseeva, Victoria et al. (2007) Solution structure of HI1506, a novel two-domain protein from Haemophilus influenzae. Protein Sci 16:977-82

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