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Biochemical Investigation of Rv3404c from Mycobacterium tuberculosis.

(2017) Biochemistry 56: 3818-3825

• PubMed: 28665588 Search on PubMedSearch on PubMed Central
• DOI: https://doi.org/10.1021/acs.biochem.7b00506
• Primary Citation of Related Structures:  
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• PubMed Abstract: 
  

  The causative agent of tuberculosis, Mycobacterium tuberculosis, is a bacterium with a complex cell wall and a complicated life cycle. The genome of M. tuberculosis contains well over 4000 genes thought to encode proteins. One of these codes for a putative enzyme referred to as Rv3404c, which has attracted research attention as a potential virulence factor for over 12 years. Here we demonstrate that Rv3404c functions as a sugar N-formyltransferase that converts dTDP-4-amino-4,6-dideoxyglucose into dTDP-4-formamido-4,6-dideoxyglucose using N ¹⁰ -formyltetrahydrofolate as the carbon source. Kinetic analyses demonstrate that Rv3404c displays a significant catalytic efficiency of 1.1 × 10 ⁴ M ^-1 s ^-1 . In addition, we report the X-ray structure of a ternary complex of Rv3404c solved in the presence of N ⁵ -formyltetrahydrofolate and dTDP-4-amino-4,6-dideoxyglucose. The final model of Rv3404c was refined to an overall R-factor of 16.8% at 1.6 Å resolution. The results described herein are especially intriguing given that there have been no published reports of N-formylated sugars associated with M. tuberculosis. The data thus provide a new avenue of research into this fascinating, yet deadly, organism that apparently has been associated with human infection since ancient times.

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Organizational Affiliation: 

Department of Biochemistry, University of Wisconsin , Madison, Wisconsin 53706, United States.