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ACS Infect Dis. 2018 Jul 13;4(7):1082-1092. doi: 10.1021/acsinfecdis.7b00237. Epub 2018 Apr 9.

Flavin Storage and Sequestration by Mycobacterium tuberculosis Dodecin.

Author information

1
Institute of Organic Chemistry and Chemical Biology, Buchmann Institute for Molecular Life Sciences, Cluster of Excellence for Macromolecular Complexes , Goethe University Frankfurt , Max-von-Laue-Str. 15 , D-60438 Frankfurt am Main , Germany.
2
Institute of Physical and Theoretical Chemistry, Cluster of Excellence for Macromolecular Complexes , Goethe University Frankfurt , Max-von-Laue-Str. 7 , D-60438 Frankfurt am Main , Germany.
3
Nöll Junior Research Group, Organic Chemistry , University of Siegen , Adolf-Reichwein-Str. 2 , D-57068 Siegen , Germany.

Abstract

Dodecins are small flavin binding proteins occurring in archaea and bacteria. They are remarkable for binding dimers of flavins with their functional relevant aromatic isoalloxazine rings deeply covered. Bacterial dodecins are widely spread and found in a large variety of pathogens, among them Pseudomonas aeruginosa, Streptococcus pneumonia, Ralstonia solanacearum, and Mycobacterium tuberculosis ( M. tuberculosis). In this work, we seek to understand the function of dodecins from M. tuberculosis dodecin. We describe flavin binding in thermodynamic and kinetic properties and achieve mechanistic insight in dodecin function by applying spectroscopic and electrochemical methods. Intriguingly, we reveal a significant pH dependence in the affinity and specificity of flavin binding. Our data give insight in M. tuberculosis dodecin function and advance the current understanding of dodecins as flavin storage and sequestering proteins. We suggest that the dodecin in M. tuberculosis may specifically be important for flavin homeostasis during the elaborate lifestyle of this organism, which calls for the evaluation of this protein as drug target.

KEYWORDS:

antibiotics; flavoenzymes; flavoproteins; homeostasis; pH control; storage protein; tuberculosis

PMID:
29608272
DOI:
10.1021/acsinfecdis.7b00237
[Indexed for MEDLINE]

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