Publication Date:
2010-06-19
Description:
Archaeal and eukaryotic translation elongation factor 2 contain a unique post-translationally modified histidine residue called diphthamide, which is the target of diphtheria toxin. The biosynthesis of diphthamide was proposed to involve three steps, with the first being the formation of a C-C bond between the histidine residue and the 3-amino-3-carboxypropyl group of S-adenosyl-l-methionine (SAM). However, further details of the biosynthesis remain 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-sulphur-cluster enzyme, Dph2. Dph2 is a homodimer and each of its monomers can bind 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(gamma,Met)-S bond of SAM and generates a 3-amino-3-carboxypropyl radical. Our results suggest that P. horikoshii Dph2 represents a previously unknown, SAM-dependent, [4Fe-4S]-containing enzyme that catalyses unprecedented chemistry.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3006227/" 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/PMC3006227/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉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 -- P41 RR016292/RR/NCRR NIH HHS/ -- P41 RR016292-01/RR/NCRR NIH HHS/ -- P41 RR016292-09/RR/NCRR NIH HHS/ -- P41 RR016292-10/RR/NCRR NIH HHS/ -- P41 RR016292-11/RR/NCRR NIH HHS/ -- P41-RR016292/RR/NCRR NIH HHS/ -- R01 GM088276/GM/NIGMS NIH HHS/ -- R01 GM088276-01/GM/NIGMS NIH HHS/ -- R01GM088276/GM/NIGMS NIH HHS/ -- RR-15301/RR/NCRR NIH HHS/ -- England -- Nature. 2010 Jun 17;465(7300):891-6. doi: 10.1038/nature09138.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Chemistry and Chemical Biology, Cornell University, Ithaca, New York 14853, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20559380" target="_blank"〉PubMed〈/a〉
Keywords:
Archaeal Proteins/*metabolism
;
Free Radicals/chemistry/*metabolism
;
Histidine/*analogs & derivatives/biosynthesis/chemistry
;
Iron-Sulfur Proteins/*metabolism
;
Pyrococcus horikoshii/*enzymology
;
S-Adenosylmethionine/metabolism
Print ISSN:
0028-0836
Electronic ISSN:
1476-4687
Topics:
Biology
,
Chemistry and Pharmacology
,
Medicine
,
Natural Sciences in General
,
Physics
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