Chapter 13 : Structural Annotation of the Proteome

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Deciphering the complete genome sequence of in 1998 ( ) marked an important milestone in tuberculosis (TB) research and has triggered a whole array of downstream research in the area. A bewildering array of omics data of the organism and genome sequences of related species is now available ( ). One of the major obstacles to ready exploitation of such huge volumes of genomics data is the lack of annotation of many of the gene products. With the architectural blueprint of the organism at hand, a logical next step is to comprehend the huge pool of data to identify and understand the function of the individual gene products.

Citation: Chandra N, Sandhya S, Anand P. 2014. Structural Annotation of the Proteome, p 261-280. In Hatfull G, Jacobs W (ed), Molecular Genetics of Mycobacteria, Second Edition. ASM Press, Washington, DC. doi: 10.1128/microbiolspec.MGM2-0027-2013
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Figure 1

Schematic diagram of proteome structural annotation. The figure depicts the circular map of the H37Rv structural proteome, corresponding to the first genome view reported with its complete genome sequence ( ). The outer circle represents the model coverage in terms of the percentage of the polypeptide chain, whereas the inner circle represents the percentage sequence identity shared by each model with its corresponding template. On both the outer and inner circles, radiating lines are drawn to indicate the parameters of the structural model for the corresponding protein in the genome view. The length of the lines in both cases is proportional to their values in percentages. The 100% mark is also shown for both the circles. In the outer circle, those models that had greater than 40% length coverage are drawn outside the circle, whereas those with coverage of less than that are drawn inside the circle (for clarity). Length coverage is divided into five classes and color coded as indicated, while the levels of sequence identity are divided into four classes and color coded as indicated. Predominantly occurring folds in the proteome are shown surrounding the outer circle, ordered clockwise by frequency of occurrence (indicated in parentheses).

Citation: Chandra N, Sandhya S, Anand P. 2014. Structural Annotation of the Proteome, p 261-280. In Hatfull G, Jacobs W (ed), Molecular Genetics of Mycobacteria, Second Edition. ASM Press, Washington, DC. doi: 10.1128/microbiolspec.MGM2-0027-2013
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Figure 2

Aspects of annotation. ERRAT output of Rv1485 showing an overall quality factor of ∼70% by evaluating the nonbonded interactions between different atom types. Superposition of Rv1485 with its template 1HRK:A. Multiple sequence alignment with selected sequence neighbors, highlighting conserved catalytic site residues (in triangles). Binding site prediction using LigsiteCSC and PocketDepth. Predicted ligand-binding pockets in red surface. The expected ligand-binding site as determined by superposing the template is shown as sticks. Association of the heme ligand to the predicted binding site (residues in red) based on high similarity to a known heme binding site by searching against PDB pockets (blue).

Citation: Chandra N, Sandhya S, Anand P. 2014. Structural Annotation of the Proteome, p 261-280. In Hatfull G, Jacobs W (ed), Molecular Genetics of Mycobacteria, Second Edition. ASM Press, Washington, DC. doi: 10.1128/microbiolspec.MGM2-0027-2013
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Figure 3

Coverage of a structural proteome. Distribution of different structural classes as described through folds, superfamilies, and families occurring in SCOP and correspondingly in the proteome adjacent to it. Distribution of structural information according to TubercuList functional categories. The inner circle represents the total number of genes in a particular functional category, and the outer circle represents the genes with structural information in the corresponding functional category.

Citation: Chandra N, Sandhya S, Anand P. 2014. Structural Annotation of the Proteome, p 261-280. In Hatfull G, Jacobs W (ed), Molecular Genetics of Mycobacteria, Second Edition. ASM Press, Washington, DC. doi: 10.1128/microbiolspec.MGM2-0027-2013
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Figure 4

Fold combination and higher-order assemblies. Network of fold combination observed in modeled multidomain proteins. Each node represents a fold, and an edge represents two folds occurring together within a polypeptide. The topmost occurring fold combination is the tetracycline-like repressor C-terminal (a.121) domain with DNA 3-helical bundle (a.4). An example protein, Rv3557c, is shown with both folds highlighted. Examples of higher-order assemblies. The predicted assembly of methylmalonyl CoA mutase derived from the structural template 1REQ is shown. The assembly consists of Rv1492, MutA (cyan), and Rv1493, MutB (green). The conserved residues that could be involved in the interaction at the interface are shown in stick representation below. Similarly, the complex of fumarate reductase generated from 1KF6 is shown below, with residues involved in quinol binding that are conserved highlighted as spheres.

Citation: Chandra N, Sandhya S, Anand P. 2014. Structural Annotation of the Proteome, p 261-280. In Hatfull G, Jacobs W (ed), Molecular Genetics of Mycobacteria, Second Edition. ASM Press, Washington, DC. doi: 10.1128/microbiolspec.MGM2-0027-2013
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Figure 5

Example annotations. Example annotation of a conserved hypothetical protein, Rv3402c. The superposition consists of a model of Rv3402c (shown in green), and the template 1MDO is shown as cyan. The conserved residues predicted to be involved in the interaction with PLP are represented as sticks. The structure-based sequence alignment of Rv3402c with the template 1MDO. Functionally important residues are marked with (*). The amino acids are colored based on their chemical properties. Superposition of Rv0469 (green) with the template 1KPG. The residues involved in cofactor recognition are shown in blue, and residues determining the substrate specificities are highlighted in red. The predicted pocket is shown in a surface representation. Superposition of Rv2503c (green) with the template 2CTZ. The pocket predicted using PocketDepth and SURFnet enclosing the active site is shown in a mesh.

Citation: Chandra N, Sandhya S, Anand P. 2014. Structural Annotation of the Proteome, p 261-280. In Hatfull G, Jacobs W (ed), Molecular Genetics of Mycobacteria, Second Edition. ASM Press, Washington, DC. doi: 10.1128/microbiolspec.MGM2-0027-2013
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