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Identification of Widespread Adenosine Nucleotide Binding in Mycobacterium Tuberculosis

Abstract

Computational prediction of protein function is frequently error-prone and incomplete. In Mycobacterium tuberculosis (Mtb), ~25% of all genes have no predicted function and are annotated as hypothetical proteins, severely limiting our understanding of Mtb pathogenicity. Here, we utilize a high-throughput quantitative activity-based protein profiling (ABPP) platform to probe, annotate, and validate ATP-binding proteins in Mtb. We experimentally validate prior in silico predictions of >240 proteins and identify 72 hypothetical proteins as ATP binders. ATP interacts with proteins with diverse and unrelated sequences, providing an expanded view of adenosine nucleotide binding in Mtb. Several hypothetical ATP binders are essential or taxonomically limited, suggesting specialized functions in mycobacterial physiology and pathogenicity.

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References
1.
Kelley L, Sternberg M . Protein structure prediction on the Web: a case study using the Phyre server. Nat Protoc. 2009; 4(3):363-71. DOI: 10.1038/nprot.2009.2. View

2.
Doerks T, van Noort V, Minguez P, Bork P . Annotation of the M. tuberculosis hypothetical orfeome: adding functional information to more than half of the uncharacterized proteins. PLoS One. 2012; 7(4):e34302. PMC: 3317503. DOI: 10.1371/journal.pone.0034302. View

3.
Sadler N, Angel T, Lewis M, Pederson L, Chauvigne-Hines L, Wiedner S . Activity-based protein profiling reveals mitochondrial oxidative enzyme impairment and restoration in diet-induced obese mice. PLoS One. 2012; 7(10):e47996. PMC: 3480472. DOI: 10.1371/journal.pone.0047996. View

4.
Galperin M, Koonin E . From complete genome sequence to 'complete' understanding?. Trends Biotechnol. 2010; 28(8):398-406. PMC: 3065831. DOI: 10.1016/j.tibtech.2010.05.006. View

5.
Qiu H, Wang Y . Probing adenosine nucleotide-binding proteins with an affinity-labeled nucleotide probe and mass spectrometry. Anal Chem. 2007; 79(15):5547-56. PMC: 2637870. DOI: 10.1021/ac0622375. View