Crystal Structures of SgcE6 and SgcC, the Two-Component Monooxygenase That Catalyzes Hydroxylation of a Carrier ProteinTethered Substrate during the Biosynthesis of the Enediyne Antitumor Antibiotic C-1027 in <i>Streptomyces globisporus</i> [electronic resource].
- Bethesda, Md. : National Institutes of Health (U.S.), 2016.
Oak Ridge, Tenn. : Distributed by the Office of Scientific and Technical Information, U.S. Dept. of Energy
- Physical Description:
- pages 5,142-5,154 : digital, PDF file
- Additional Creators:
- Argonne National Laboratory
National Institutes of Health (U.S.)
United States. Department of Energy. Office of Science
Scripps Research Institute
United States. Department of Energy. Office of Scientific and Technical Information
- C-1027 is a chromoprotein enediyne antitumor antibiotic produced by <i>Streptomyces globisporus</i>. In the last step of biosynthesis of the (S)-3-chloro-5-hydroxy-beta-tyrosine moiety of the C-1027 enediyne chromophore, SgcE6 and SgcC compose a two-component monooxygenase that hydroxylates the C-5 position of (S)-3-chloro-beta-tyrosine. This two-component monooxygenase is remarkable for two reasons. (i) SgcE6 specifically reacts with FAD and NADH, and (ii) SgcC is active with only the peptidyl carrier protein (PCP)-tethered substrate. To address the molecular details of substrate specificity, we determined the crystal structures of SgcE6 and SgcC at 1.66 and 2.63 A resolution, respectively. SgcE6 shares a similar β-barrel fold with the class I HpaC-like flavin reductases. A flexible loop near the active site of SgcE6 plays a role in FAD binding, likely by providing sufficient space to accommodate the AMP moiety of FAD, when compared to that of FMN-utilizing homologues. SgcC shows structural similarity to a few, other known FADH<sub>2</sub>-dependent monooxygenases and sheds light on some biochemically but not structurally characterized homologues. In conclusion, the crystal structures reported here provide insights into substrate specificity, and comparison with homologues provides a catalytic mechanism of the two-component, FADH<sub>2</sub>-dependent monooxygenase (SgcE6 and SgcC) that catalyzes the hydroxylation of a PCP-tethered substrate.
- Published through SciTech Connect.
Biochemistry 55 36 ISSN 0006-2960 AM
Chin -Yuan Chang; Jeremy Lohman; Hongnan Cao; Kemin Tan; Jeffrey D. Rudolf; Ming Ma; Weijun Xu; Craig A. Bingman; Ragothaman M. Yennamalli; Lance Bigelow; Gyorgy Babnigg; Xiaohui Yan; Andrzej Joachimiak; George N. Phillips, Jr.; Ben Shen.
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