6BXM

Crystal structure of Candidatus Methanoperedens nitroreducens Dph2 with 4Fe-4S cluster and SAM/cleaved SAM

Summary for 6BXM

• Entry DOI: 10.2210/pdb6bxm/pdb
• Descriptor: Diphthamide biosynthesis enzyme Dph2, IRON/SULFUR CLUSTER, S-ADENOSYLMETHIONINE, ... (6 entities in total)
• Functional Keywords: diphthamide biosynthesis, radical sam enzyme, biosynthetic protein
• Biological source: Candidatus Methanoperedens nitroreducens
• Total number of polymer chains: 2
• Total formula weight: 74420.84

Authors

Fenwick, M.K.,Torelli, A.T.,Zhang, Y.,Dong, M.,Kathiresan, V.,Carantoa, J.D.,Dzikovski, B.,Lancaster, K.M.,Freed, J.H.,Hoffman, B.M.,Lin, H.,Ealick, S.E. (deposition date: 2017-12-18, release date: 2018-04-11, Last modification date: 2023-11-15)

Primary citation

Dong, M.,Kathiresan, V.,Fenwick, M.K.,Torelli, A.T.,Zhang, Y.,Caranto, J.D.,Dzikovski, B.,Sharma, A.,Lancaster, K.M.,Freed, J.H.,Ealick, S.E.,Hoffman, B.M.,Lin, H.
Organometallic and radical intermediates reveal mechanism of diphthamide biosynthesis.
Science, 359:1247-1250, 2018

PubMed Abstract: Diphthamide biosynthesis involves a carbon-carbon bond-forming reaction catalyzed by a radical S-adenosylmethionine (SAM) enzyme that cleaves a carbon-sulfur (C-S) bond in SAM to generate a 3-amino-3-carboxypropyl (ACP) radical. Using rapid freezing, we have captured an organometallic intermediate with an iron-carbon (Fe-C) bond between ACP and the enzyme's [4Fe-4S] cluster. In the presence of the substrate protein, elongation factor 2, this intermediate converts to an organic radical, formed by addition of the ACP radical to a histidine side chain. Crystal structures of archaeal diphthamide biosynthetic radical SAM enzymes reveal that the carbon of the SAM C-S bond being cleaved is positioned near the unique cluster Fe, able to react with the cluster. Our results explain how selective C-S bond cleavage is achieved in this radical SAM enzyme.

PubMed: 29590073
DOI: 10.1126/science.aao6595

Experimental method

X-RAY DIFFRACTION (2.252 Å)