Publication Date:
2014-11-05
Description:
Lantibiotics are a class of peptide antibiotics that contain one or more thioether bonds. The lantibiotic nisin is an antimicrobial peptide that is widely used as a food preservative to combat food-borne pathogens. Nisin contains dehydroalanine and dehydrobutyrine residues that are formed by the dehydration of Ser/Thr by the lantibiotic dehydratase NisB (ref. 2). Recent biochemical studies revealed that NisB glutamylates Ser/Thr side chains as part of the dehydration process. However, the molecular mechanism by which NisB uses glutamate to catalyse dehydration remains unresolved. Here we show that this process involves glutamyl-tRNA(Glu) to activate Ser/Thr residues. In addition, the 2.9-A crystal structure of NisB in complex with its substrate peptide NisA reveals the presence of two separate domains that catalyse the Ser/Thr glutamylation and glutamate elimination steps. The co-crystal structure also provides insights into substrate recognition by lantibiotic dehydratases. Our findings demonstrate an unexpected role for aminoacyl-tRNA in the formation of dehydroamino acids in lantibiotics, and serve as a basis for the functional characterization of the many lantibiotic-like dehydratases involved in the biosynthesis of other classes of natural products.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4430201/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉 〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4430201/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ortega, Manuel A -- Hao, Yue -- Zhang, Qi -- Walker, Mark C -- van der Donk, Wilfred A -- Nair, Satish K -- 5T32-GM070421/GM/NIGMS NIH HHS/ -- F32 GM112284/GM/NIGMS NIH HHS/ -- R01 GM 058822/GM/NIGMS NIH HHS/ -- R01 GM058822/GM/NIGMS NIH HHS/ -- R01 GM079038/GM/NIGMS NIH HHS/ -- S10 RR027109 A/RR/NCRR NIH HHS/ -- T32 GM070421/GM/NIGMS NIH HHS/ -- England -- Nature. 2015 Jan 22;517(7535):509-12. doi: 10.1038/nature13888. Epub 2014 Oct 26.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biochemistry, University of Illinois at Urbana-Champaign, 600 South Mathews Avenue, Urbana, Illinois 61801, USA. ; Department of Chemistry and Howard Hughes Medical Institute, University of Illinois at Urbana-Champaign, 600 South Mathews Avenue, Urbana, Illinois 61801, USA. ; 1] Department of Biochemistry, University of Illinois at Urbana-Champaign, 600 South Mathews Avenue, Urbana, Illinois 61801, USA [2] Department of Chemistry and Howard Hughes Medical Institute, University of Illinois at Urbana-Champaign, 600 South Mathews Avenue, Urbana, Illinois 61801, USA. ; 1] Department of Biochemistry, University of Illinois at Urbana-Champaign, 600 South Mathews Avenue, Urbana, Illinois 61801, USA [2] Center for Biophysics and Computational Biology, University of Illinois at Urbana-Champaign, 600 South Mathews Avenue, Urbana, Illinois 61801, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25363770" target="_blank"〉PubMed〈/a〉
Keywords:
Bacterial Proteins/*chemistry/classification/*metabolism
;
Bacteriocins/biosynthesis/*metabolism
;
Crystallography, X-Ray
;
Escherichia coli/genetics
;
Glutamic Acid/metabolism
;
Hydro-Lyases/*chemistry/classification/*metabolism
;
Lactococcus lactis/*enzymology/genetics
;
Membrane Proteins/*chemistry/classification/*metabolism
;
Models, Molecular
;
Nisin/biosynthesis/metabolism
;
Phylogeny
;
Protein Structure, Tertiary
;
RNA, Transfer, Glu/genetics/*metabolism
;
Serine/metabolism
;
Threonine/metabolism
Print ISSN:
0028-0836
Electronic ISSN:
1476-4687
Topics:
Biology
,
Chemistry and Pharmacology
,
Medicine
,
Natural Sciences in General
,
Physics
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