Using MbtH-Like Proteins to Alter the Substrate Profile of a Nonribosomal Peptide Adenylation Enzyme
Journal Article
·
· ChemBioChem: a European journal of chemical biology
- Department of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, Lee T. Todd, Jr. Building 789 South Limestone St. Lexington KY 40536-0596 USA
- University of Washington, Center for Emerging and Re-emerging Infectious Diseases, 750 Republican St. Seattle WA 98109 USA; University of Washington, Seattle Structural Genomics Center for Infectious Diseases, 307 Westlake Avenue N Seattle WA 98109 USA
- University of Washington, Seattle Structural Genomics Center for Infectious Diseases, 307 Westlake Avenue N Seattle WA 98109 USA; Earth and Biological Sciences Directorate, Pacific Northwest National Laboratory, P. O. Box 999 Richmond WA 99352 USA; School of Molecular Biosciences, Washington State University, P. O. Box 647520 Pullman WA 99164 USA
- Department of Molecular and Cellular Biochemistry, College of Medicine, University of Kentucky, Biological Sciences Research Bldg 741 South Limestone St. Lexington KY 40536-0509 USA
MbtH-like proteins (MLPs) are required for soluble expression and/or optimal activity of some adenylation (A) domains of nonribosomal peptide synthetases (NRPSs). Since A domains can interact with noncognate MLP partners, we investigated how the function of an A domain, TioK, involved in the biosynthesis of the bisintercalator thiocoraline, is altered by noncognate MLPs. Measuring TioK activity with 12 different MLPs from a variety of bacterial species using a radiometric assay suggested that the A domain substrate promiscuity could be altered by foreign MLPs. Kinetic studies and bioinformatics analysis indicated that MLPs’ functions are not as simple as previously thought.
- Research Organization:
- Pacific Northwest National Lab. (PNNL), Richland, WA (United States)
- Sponsoring Organization:
- USDOE
- DOE Contract Number:
- AC05-76RL01830
- OSTI ID:
- 1503572
- Report Number(s):
- PNNL-SA-131568
- Journal Information:
- ChemBioChem: a European journal of chemical biology, Vol. 19, Issue 20; ISSN 1439-4227
- Publisher:
- ChemPubSoc Europe
- Country of Publication:
- United States
- Language:
- English
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