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Diphthamide biosynthesis requires an Fe-S enzyme-generated organic radical
Archaeal and eukaryotic translation elongation factor 2 contain a unique posttranslationally modified histidine residue called “diphthamide”, the target of diphtheria toxin. The biosynthesis of diphthamide were proposed to involve three steps, with the first step being the formation of a C-C bond be...
Autores principales: | , , , , , , , , , , |
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Formato: | Texto |
Lenguaje: | English |
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2010
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3006227/ https://www.ncbi.nlm.nih.gov/pubmed/20559380 http://dx.doi.org/10.1038/nature09138 |
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author | Zhang, Yang Zhu, Xuling Torelli, Andrew T. Lee, Michael Dzikovski, Boris Koralewski, Rachel M. Wang, Eileen Freed, Jack Krebs, Carsten Ealick, Steven E. Lin, Hening |
author_facet | Zhang, Yang Zhu, Xuling Torelli, Andrew T. Lee, Michael Dzikovski, Boris Koralewski, Rachel M. Wang, Eileen Freed, Jack Krebs, Carsten Ealick, Steven E. Lin, Hening |
author_sort | Zhang, Yang |
collection | PubMed |
description | Archaeal and eukaryotic translation elongation factor 2 contain a unique posttranslationally modified histidine residue called “diphthamide”, the target of diphtheria toxin. The biosynthesis of diphthamide were proposed to involve three steps, with the first step being the formation of a C-C bond between the histidine residue and the 3-amino-3-carboxypropyl group of S-adenosylmethionine (SAM). However, details of the biosynthesis have remained unknown. Here we present structural and biochemical evidence showing that the first step of diphthamide biosynthesis in the archaeon Pyrococcus horikoshii uses a novel iron-sulfur cluster enzyme, Dph2. Dph2 is a homodimer and each monomer contains a [4Fe-4S] cluster. Biochemical data suggest that unlike the enzymes in the radical SAM superfamily, Dph2 does not form the canonical 5′-deoxyadenosyl radical. Instead, it breaks the C(γ,Met)-S bond of SAM and generates a 3-amino-3-carboxylpropyl radical. This work suggests that Pyrococcus horikoshii Dph2 represents a novel SAM-dependent [4Fe-4S]-containing enzyme that catalyzes unprecedented chemistry. |
format | Text |
id | pubmed-3006227 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2010 |
record_format | MEDLINE/PubMed |
spelling | pubmed-30062272010-12-21 Diphthamide biosynthesis requires an Fe-S enzyme-generated organic radical Zhang, Yang Zhu, Xuling Torelli, Andrew T. Lee, Michael Dzikovski, Boris Koralewski, Rachel M. Wang, Eileen Freed, Jack Krebs, Carsten Ealick, Steven E. Lin, Hening Nature Article Archaeal and eukaryotic translation elongation factor 2 contain a unique posttranslationally modified histidine residue called “diphthamide”, the target of diphtheria toxin. The biosynthesis of diphthamide were proposed to involve three steps, with the first step being the formation of a C-C bond between the histidine residue and the 3-amino-3-carboxypropyl group of S-adenosylmethionine (SAM). However, details of the biosynthesis have remained unknown. Here we present structural and biochemical evidence showing that the first step of diphthamide biosynthesis in the archaeon Pyrococcus horikoshii uses a novel iron-sulfur cluster enzyme, Dph2. Dph2 is a homodimer and each monomer contains a [4Fe-4S] cluster. Biochemical data suggest that unlike the enzymes in the radical SAM superfamily, Dph2 does not form the canonical 5′-deoxyadenosyl radical. Instead, it breaks the C(γ,Met)-S bond of SAM and generates a 3-amino-3-carboxylpropyl radical. This work suggests that Pyrococcus horikoshii Dph2 represents a novel SAM-dependent [4Fe-4S]-containing enzyme that catalyzes unprecedented chemistry. 2010-06-17 /pmc/articles/PMC3006227/ /pubmed/20559380 http://dx.doi.org/10.1038/nature09138 Text en Users may view, print, copy, download and text and data- mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use: http://www.nature.com/authors/editorial_policies/license.html#terms |
spellingShingle | Article Zhang, Yang Zhu, Xuling Torelli, Andrew T. Lee, Michael Dzikovski, Boris Koralewski, Rachel M. Wang, Eileen Freed, Jack Krebs, Carsten Ealick, Steven E. Lin, Hening Diphthamide biosynthesis requires an Fe-S enzyme-generated organic radical |
title | Diphthamide biosynthesis requires an Fe-S enzyme-generated organic radical |
title_full | Diphthamide biosynthesis requires an Fe-S enzyme-generated organic radical |
title_fullStr | Diphthamide biosynthesis requires an Fe-S enzyme-generated organic radical |
title_full_unstemmed | Diphthamide biosynthesis requires an Fe-S enzyme-generated organic radical |
title_short | Diphthamide biosynthesis requires an Fe-S enzyme-generated organic radical |
title_sort | diphthamide biosynthesis requires an fe-s enzyme-generated organic radical |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3006227/ https://www.ncbi.nlm.nih.gov/pubmed/20559380 http://dx.doi.org/10.1038/nature09138 |
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