MIT Libraries logoDSpace@MIT

MIT
View Item 
  • DSpace@MIT Home
  • MIT Open Access Articles
  • MIT Open Access Articles
  • View Item
  • DSpace@MIT Home
  • MIT Open Access Articles
  • MIT Open Access Articles
  • View Item
JavaScript is disabled for your browser. Some features of this site may not work without it.

An Unusual Role for a Mobile Flavin in StaC-like Indolocarbazole Biosynthetic Enzymes

Author(s)
Goldman, Peter J.; Hamill, Michael J.; Howard-Jones, Annaleise R.; Walsh, Christopher T.; Elliott, Sean J.; Drennan, Catherine L.; Ryan, Katherine S.; Ryan, Katherine S.; ... Show more Show less
Thumbnail
DownloadDrennan_An unusual role.pdf (1.809Mb)
PUBLISHER_POLICY

Publisher Policy

Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use.

Terms of use
Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use.
Metadata
Show full item record
Abstract
The indolocarbazole biosynthetic enzymes StaC, InkE, RebC, and AtmC mediate the degree of oxidation of chromopyrrolic acid on route to the natural products staurosporine, K252a, rebeccamycin, and AT2433-A1, respectively. Here, we show that StaC and InkE, which mediate a net 4-electron oxidation, bind FAD with a micromolar Kd, whereas RebC and AtmC, which mediate a net 8-electron oxidation, bind FAD with a nanomolar Kd while displaying the same FAD redox properties. We further create RebC-10x, a RebC protein with ten StaC-like amino acid substitutions outside of previously characterized FAD-binding motifs and the complementary StaC-10x. We find that these mutations mediate both FAD affinity and product specificity, with RebC-10x displaying higher StaC activity than StaC itself. X-ray structures of this StaC catalyst identify the substrate of StaC as 7-carboxy-K252c and suggest a unique mechanism for this FAD-dependent enzyme.
Date issued
2012-07
URI
http://hdl.handle.net/1721.1/82020
Department
Massachusetts Institute of Technology. Department of Biology; Massachusetts Institute of Technology. Department of Chemistry
Journal
Chemistry & Biology
Publisher
Springer Science + Business Media B.V.
Citation
Goldman, Peter J., Katherine S. Ryan, Michael J. Hamill, Annaleise R. Howard-Jones, Christopher T. Walsh, Sean J. Elliott, and Catherine L. Drennan. “An Unusual Role for a Mobile Flavin in StaC-like Indolocarbazole Biosynthetic Enzymes.” Chemistry & Biology 19, no. 7 (July 2012): 855-865.
Version: Author's final manuscript
ISSN
10745521

Collections
  • MIT Open Access Articles

Browse

All of DSpaceCommunities & CollectionsBy Issue DateAuthorsTitlesSubjectsThis CollectionBy Issue DateAuthorsTitlesSubjects

My Account

Login

Statistics

OA StatisticsStatistics by CountryStatistics by Department
MIT Libraries
PrivacyPermissionsAccessibilityContact us
MIT
Content created by the MIT Libraries, CC BY-NC unless otherwise noted. Notify us about copyright concerns.