5EHK

Crystal structure of tRNA dependent lantibiotic dehydratase MibB from Microbispora sp. 107891

Summary for 5EHK

• Entry DOI: 10.2210/pdb5ehk/pdb
• Descriptor: Lantibiotic dehydratase (2 entities in total)
• Functional Keywords: lantibiotic dehydratase, nai-107, microbispora sp. 107891, trna dependent, hydrolase
• Biological source: Microbispora corallina
• Total number of polymer chains: 2
• Total formula weight: 243743.95

Authors

Hao, Y.,Nair, S.K. (deposition date: 2015-10-28, release date: 2016-03-02, Last modification date: 2024-03-06)

Primary citation

Ortega, M.A.,Hao, Y.,Walker, M.C.,Donadio, S.,Sosio, M.,Nair, S.K.,van der Donk, W.A.
Structure and tRNA Specificity of MibB, a Lantibiotic Dehydratase from Actinobacteria Involved in NAI-107 Biosynthesis.
Cell Chem Biol, 23:370-380, 2016

PubMed Abstract: Class I lantibiotic dehydratases dehydrate selected Ser/Thr residues of a precursor peptide. Recent studies demonstrated the requirement of glutamyl-tRNA(Glu) for Ser/Thr activation by one of these enzymes (NisB) from the Firmicute Lactococcus lactis. However, the generality of glutamyl-tRNA(Glu) usage and the tRNA specificity of lantibiotic dehydratases have not been established. Here we report the 2.7-Å resolution crystal structure, along with the glutamyl-tRNA(Glu) utilization of MibB, a lantibiotic dehydratase from the Actinobacterium Microbispora sp. 107891 involved in the biosynthesis of the clinical candidate NAI-107. Biochemical assays revealed nucleotides A73 and U72 within the tRNA(Glu) acceptor stem to be important for MibB glutamyl-tRNA(Glu) usage. Using this knowledge, an expression system for the production of NAI-107 analogs in Escherichia coli was developed, overcoming the inability of MibB to utilize E. coli tRNA(Glu). Our work provides evidence for a common tRNA(Glu)-dependent dehydration mechanism, paving the way for the characterization of lantibiotics from various phyla.

PubMed: 26877024
DOI: 10.1016/j.chembiol.2015.11.017

Experimental method

X-RAY DIFFRACTION (2.708 Å)