U.S. Department of Energy

Pacific Northwest National Laboratory

Identification of widespread adenosine nucleotide binding in Mycobacterium tuberculosis.

TitleIdentification of widespread adenosine nucleotide binding in Mycobacterium tuberculosis.
Publication TypeJournal Article
Year of Publication2013
AuthorsAnsong C, Ortega C, Payne SH, Haft DH, Chauvignè-Hines LM, Lewis MP, Ollodart AR, Purvine SO, Shukla AK, Fortuin S, Smith RD, Adkins JN, Grundner C, Wright AT
JournalChem Biol
KeywordsAdenosine, Adenosine Triphosphate, Amino Acid Sequence, Bacterial Proteins, Computer Simulation, Humans, Models, Biological, Molecular Sequence Data, Mycobacterium tuberculosis, Protein Binding, Proteomics, 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.

DOI10.1016/j.chembiol.2012.11.008
PubMed ID23352146
PubMed Central IDPMC3558932
Grant List8P41GM103493-10 / GM / NIGMS NIH HHS / United States
P30AI027757 / AI / NIAID NIH HHS / United States
P41 GM103493 / GM / NIGMS NIH HHS / United States
R01 HG004881 / HG / NHGRI NIH HHS / United States
R01 HG004881 / HG / NHGRI NIH HHS / United States
Area of Research: 
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