Chapter 11 : TB or Not TB: a Structural Genomics Mission?

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This chapter describes the experimental path from gene to protein structure, the public tuberculosis (TB) structural henomics consortium database, and the structures that have been determined thus far and their biological relevance. Structural genomics is the determination and analysis of protein structures on a genome-wide scale, proceeding from knowledge of the genome sequence to knowledge of the three-dimensional structure. One of the goals of structural genomics is to determine example structures for new protein families, so that three-dimensional structural models may be constructed with no structural information. Another goal is functional annotation of proteins with no known function by analysis of their atomic structures. A third goal is to construct protein-protein interaction networks of an entire genome. Lastly, for structural genomics projects to fulfill their goals, the process must be automated for high throughput. Proteins are secreted by in response to environmental changes, for example, to protect against oxidative damage or to colonize a host successfully. The antigen 85 complex comprises three closely related enzymes, antigen 85A (Ag85A) (31 kDa), Ag85B (30 kDa), and Ag85C (31.5 kDa). These secreted proteins are both antigenic and involved in cell wall maintenance. The secreted antigen MPT70 and its homolog MPT83 (63% sequence identical) are highly immunogenic during the infection of mice. Phosphatidylinositol is a key precursor of many glycolipid cell wall components.

Citation: Goulding C, Pal D, Eisenberg D. 2005. TB or Not TB: a Structural Genomics Mission?, p 165-179. In Cole S, Eisenach K, McMurray D, Jacobs, Jr. W (ed), Tuberculosis and the Tubercle Bacillus. ASM Press, Washington, DC. doi: 10.1128/9781555817657.ch11

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Nuclear Magnetic Resonance Spectroscopy
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Figure 1

Flowchart showing the most common experimental path for the determination of structures by members of the TB Structural Genomics Consortium, although many variations of this path are taken in practice.

Citation: Goulding C, Pal D, Eisenberg D. 2005. TB or Not TB: a Structural Genomics Mission?, p 165-179. In Cole S, Eisenach K, McMurray D, Jacobs, Jr. W (ed), Tuberculosis and the Tubercle Bacillus. ASM Press, Washington, DC. doi: 10.1128/9781555817657.ch11
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Figure 2

(A) The number of proteins (axis) that have reached each experimental stage (axis). The curve represents an exponential fit of the form = 2113.2 exp (-0.2963); = 0.9834. (B) Number of experiments conducted for all proteins at each given experimental stage.

Citation: Goulding C, Pal D, Eisenberg D. 2005. TB or Not TB: a Structural Genomics Mission?, p 165-179. In Cole S, Eisenach K, McMurray D, Jacobs, Jr. W (ed), Tuberculosis and the Tubercle Bacillus. ASM Press, Washington, DC. doi: 10.1128/9781555817657.ch11
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Table 1

Information about protein structures determined by consortium nonmembers prior to 1998

Citation: Goulding C, Pal D, Eisenberg D. 2005. TB or Not TB: a Structural Genomics Mission?, p 165-179. In Cole S, Eisenach K, McMurray D, Jacobs, Jr. W (ed), Tuberculosis and the Tubercle Bacillus. ASM Press, Washington, DC. doi: 10.1128/9781555817657.ch11
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PDB ID codes for structures in this chapter not in Color Plate 6

Citation: Goulding C, Pal D, Eisenberg D. 2005. TB or Not TB: a Structural Genomics Mission?, p 165-179. In Cole S, Eisenach K, McMurray D, Jacobs, Jr. W (ed), Tuberculosis and the Tubercle Bacillus. ASM Press, Washington, DC. doi: 10.1128/9781555817657.ch11

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