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

Abstract

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.

Authors:
 [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.
Publication Date:
Research Org.:
Argonne National Lab. (ANL), Argonne, IL (United States)
Sponsoring Org.:
USDOE Office of Science (SC); National Institutes of Health (NIH)
OSTI Identifier:
1177427
Grant/Contract Number:  
AC02-06CH11357
Resource Type:
Journal Article: Accepted Manuscript
Journal Name:
Nature Communications
Additional Journal Information:
Journal Volume: 6; Journal ID: ISSN 2041-1723
Publisher:
Nature Publishing Group
Country of Publication:
United States
Language:
ENGLISH
Subject:
59 BASIC BIOLOGICAL SCIENCES

Citation Formats

Fenwick, Michael K., Mehta, Angad P., Zhang, Yang, Abdelwahed, Sameh H., Begley, Tadhg P., and Ealick, Steven E. Non-canonical active site architecture of the radical SAM thiamin pyrimidine synthase. United States: N. p., 2015. Web. doi:10.1038/ncomms7480.
Fenwick, Michael K., Mehta, Angad P., Zhang, Yang, Abdelwahed, Sameh H., Begley, Tadhg P., & Ealick, Steven E. Non-canonical active site architecture of the radical SAM thiamin pyrimidine synthase. United States. doi:10.1038/ncomms7480.
Fenwick, Michael K., Mehta, Angad P., Zhang, Yang, Abdelwahed, Sameh H., Begley, Tadhg P., and Ealick, Steven E. Fri . "Non-canonical active site architecture of the radical SAM thiamin pyrimidine synthase". United States. doi:10.1038/ncomms7480. https://www.osti.gov/servlets/purl/1177427.
@article{osti_1177427,
title = {Non-canonical active site architecture of the radical SAM thiamin pyrimidine synthase},
author = {Fenwick, Michael K. and Mehta, Angad P. and Zhang, Yang and Abdelwahed, Sameh H. and Begley, Tadhg P. and Ealick, Steven E.},
abstractNote = {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.},
doi = {10.1038/ncomms7480},
journal = {Nature Communications},
number = ,
volume = 6,
place = {United States},
year = {Fri Mar 27 00:00:00 EDT 2015},
month = {Fri Mar 27 00:00:00 EDT 2015}
}

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Cited by: 7 works
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