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Title: Non-canonical active site architecture of the radical SAM thiamin pyrimidine synthase

Journal Article · · Nature Communications
DOI:https://doi.org/10.1038/ncomms7480· OSTI ID:1177427
 [1];  [2];  [1];  [2];  [2];  [1]
  1. Cornell Univ., Ithaca, NY (United States). Dept. of Chemistry and Chemical Biology.
  2. Texas A&M University, College Station, TX (United States). Dept. of Chemistry.
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Radical S-adenosylmethionine (SAM) enzymes use a [4Fe-4S] cluster to generate a 5'-deoxyadenosyl radical. Canonical radical SAM enzymes are characterized by a β-barrel-like fold and SAM anchors to the differentiated iron of the cluster, which is located near the amino terminus and within the β-barrel, through its amino and carboxylate groups. Here we show that ThiC, the thiamin pyrimidine synthase in plants and bacteria, contains a tethered cluster-binding domain at its carboxy terminus that moves in and out of the active site during catalysis. In contrast to canonical radical SAM enzymes, we predict that SAM anchors to an additional active site metal through its amino and carboxylate groups. Superimposition of the catalytic domains of ThiC and glutamate mutase shows that these two enzymes share similar active site architectures, thus providing strong evidence for an evolutionary link between the radical SAM and adenosylcobalamin-dependent enzyme superfamilies.

Research Organization:
Argonne National Laboratory (ANL), Argonne, IL (United States)
Sponsoring Organization:
USDOE Office of Science (SC); National Institutes of Health (NIH)
Grant/Contract Number:
AC02-06CH11357
OSTI ID:
1177427
Journal Information:
Nature Communications, Vol. 6; ISSN 2041-1723
Publisher:
Nature Publishing GroupCopyright Statement
Country of Publication:
United States
Language:
ENGLISH
Citation Metrics:
Cited by: 22 works
Citation information provided by
Web of Science

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Cited By (4)

Organometallic and radical intermediates reveal mechanism of diphthamide biosynthesis journal March 2018
C–C bond forming radical SAM enzymes involved in the construction of carbon skeletons of cofactors and natural products journal January 2018
The plastidial Arabidopsis thaliana NFU1 protein binds and delivers [4Fe-4S] clusters to specific client proteins journal January 2020
Roles and maturation of iron–sulfur proteins in plastids journal January 2018

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