4HX6

Streptomyces globisporus C-1027 NADH:FAD oxidoreductase SgcE6

Summary for 4HX6

• Entry DOI: 10.2210/pdb4hx6/pdb
• Related: 4OO2 4R82
• Descriptor: Oxidoreductase, SULFATE ION, ACETATE ION, ... (4 entities in total)
• Functional Keywords: structural genomics, psi-biology, protein structure initiative, midwest center for structural genomics, mcsg, enzyme discovery for natural product biosynthesis, natpro, oxidoreductase
• Biological source: Streptomyces globisporus
• Total number of polymer chains: 8
• Total formula weight: 160471.17

Authors

Tan, K.,Bigelow, L.,Clancy, S.,Babnigg, G.,Bingman, C.A.,Yennamalli, R.,Lohman, J.R.,Ma, M.,Shen, B.,Phillips Jr., G.N.,Joachimiak, A.,Midwest Center for Structural Genomics (MCSG),Enzyme Discovery for Natural Product Biosynthesis (NatPro) (deposition date: 2012-11-09, release date: 2012-11-28, Last modification date: 2016-12-07)

Primary citation

Chang, C.Y.,Lohman, J.R.,Cao, H.,Tan, K.,Rudolf, J.D.,Ma, M.,Xu, W.,Bingman, C.A.,Yennamalli, R.M.,Bigelow, L.,Babnigg, G.,Yan, X.,Joachimiak, A.,Phillips, G.N.,Shen, B.
Crystal Structures of SgcE6 and SgcC, the Two-Component Monooxygenase That Catalyzes Hydroxylation of a Carrier Protein-Tethered Substrate during the Biosynthesis of the Enediyne Antitumor Antibiotic C-1027 in Streptomyces globisporus.
Biochemistry, 55:5142-5154, 2016

PubMed Abstract: C-1027 is a chromoprotein enediyne antitumor antibiotic produced by Streptomyces globisporus. In the last step of biosynthesis of the (S)-3-chloro-5-hydroxy-β-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-β-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 Å 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 FADH2-dependent monooxygenases and sheds light on some biochemically but not structurally characterized homologues. The crystal structures reported here provide insights into substrate specificity, and comparison with homologues provides a catalytic mechanism of the two-component, FADH2-dependent monooxygenase (SgcE6 and SgcC) that catalyzes the hydroxylation of a PCP-tethered substrate.

PubMed: 27560143
DOI: 10.1021/acs.biochem.6b00713

Experimental method

X-RAY DIFFRACTION (1.89 Å)