Crystal Structure of Thioesterase SgcE10 Supporting Common Polyene Intermediates in 9- and 10-Membered Enediyne Core Biosynthesis [electronic resource].
- Published
- Washington, D.C. : United States. Dept. of Energy. Office of Science, 2017.
Oak Ridge, Tenn. : Distributed by the Office of Scientific and Technical Information, U.S. Dept. of Energy - Physical Description
- pages 5,159-5,169 : digital, PDF file
- Additional Creators
- Argonne National Laboratory, United States. Department of Energy. Office of Science, National Institutes of Health (U.S.), Scripps Research Institute, and United States. Department of Energy. Office of Scientific and Technical Information
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- Restrictions on Access
- Free-to-read Unrestricted online access
- Summary
- Enediynes are potent natural product anticancer antibiotics, and are classified as 9- or 10-membered according to the size of their enediyne core carbon skeleton. Both 9- and 10-membered enediyne cores are biosynthesized by the enediyne polyketide synthase (PKSE), thioesterase (TE), and PKSE-associated enzymes. Though the divergence between 9- and 10-membered enediyne core biosynthesis remains unclear, it has been observed that nascent polyketide intermediates, tethered to the acyl carrier protein (ACP) domain of PKSE, could be released by TE in the absence of the PKSE-associated enzymes. Here, we determined the crystal structure of SgcE10, the TE that participates in the biosynthesis of the 9-membered enediyne C-1027. Structural comparison of SgcE10 with CalE7 and DynE7, two TEs that participate in the biosynthesis of the 10-membered enediynes calicheamicin and dynemicin, respectively, revealed that they share a common α/β hot-dog fold. The amino acids involved in both substrate binding and catalysis are conserved among SgcE10, CalE7, and DynE7. The volume and the shape of the substrate-binding channel and active site in SgcE10, CalE7, and DynE7 confirm that TEs from both 9- and 10-membered enediyne biosynthetic machineries bind the linear form of similar ACP-tethered polyene intermediates. Taken together, our findings further support the proposal that the divergence between 9- and 10-membered enediyne core biosynthesis occurs beyond PKSE and TE catalysis.
- Report Numbers
- E 1.99:1393895
- Subject(s)
- Other Subject(s)
- Note
- Published through SciTech Connect.
08/30/2017.
"138089"
ACS Omega 2 8 ISSN 2470-1343 AM
Thibault Annaval; Jeffrey D. Rudolf; Chin-Yuan Chang; Jeremy R. Lohman; Youngchang Kim; Lance Bigelow; Robert Jedrzejczak; Gyorgy Babnigg; Andrzej Joachimiak; George N. Phillips; Ben Shen.
Arnold and Mabel Beckman Foundation - Funding Information
- AC02-06CH11357
AC02-06CH113
GM098248
CA078747
GM115575
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