A genome-wide structure-based survey of nucleotide binding proteins in M. tuberculosis

Bhagavat, Raghu ; Kim, Heung-Bok ; Kim, Chang-Yub ; Terwilliger, Thomas C. ; Mehta, Dolly ; Srinivasan, Narayanaswamy ; Chandra, Nagasuma A genome-wide structure-based survey of nucleotide binding proteins in M. tuberculosis Scientific Reports, 7 . Article ID 12489. ISSN 2045-2322

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Official URL: https://www.nature.com/articles/s41598-017-12471-8

Related URL: http://dx.doi.org/10.1038/s41598-017-12471-8


Nucleoside tri-phosphates (NTP) form an important class of small molecule ligands that participate in, and are essential to a large number of biological processes. Here, we seek to identify the NTP binding proteome (NTPome) in M. tuberculosis (M.tb), a deadly pathogen. Identifying the NTPome is useful not only for gaining functional insights of the individual proteins but also for identifying useful drug targets. From an earlier study, we had structural models of M.tb at a proteome scale from which a set of 13,858 small molecule binding pockets were identified. We use a set of NTP binding sub-structural motifs derived from a previous study and scan the M.tb pocketome, and find that 1,768 proteins or 43% of the proteome can theoretically bind NTP ligands. Using an experimental proteomics approach involving dye-ligand affinity chromatography, we confirm NTP binding to 47 different proteins, of which 4 are hypothetical proteins. Our analysis also provides the precise list of binding site residues in each case, and the probable ligand binding pose. As the list includes a number of known and potential drug targets, the identification of NTP binding can directly facilitate structure-based drug design of these targets.

Item Type:Article
Source:Copyright of this article belongs to Nature Publishing Group.
Keywords:Computational Biology and Bioinformatics; Diseases
ID Code:112534
Deposited On:19 Apr 2018 05:01
Last Modified:19 Apr 2018 05:01

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