9L11

Crystal structure of flavin reductase (StnC) complexed with FAD

Summary for 9L11

• Entry DOI: 10.2210/pdb9l11/pdb
• Descriptor: FMN dependent NADH:quinone oxidoreductase, FLAVIN-ADENINE DINUCLEOTIDE (3 entities in total)
• Functional Keywords: reductase, flavoprotein
• Biological source: Streptomyces albus
• Total number of polymer chains: 2
• Total formula weight: 51379.94

Authors

Xie, X.,Lin, S. (deposition date: 2024-12-13, release date: 2025-11-19)

Primary citation

Xie, X.,Wang, X.,Yang, X.,Ji, S.,Ouyang, X.,Zhou, Z.,Xiao, Z.,Guo, W.,Liang, R.,Huang, T.,Deng, Z.,Zhao, Y.L.,Lin, S.
A new family of StnC-like pseudo-FMN-preferred reductase components in two-component flavoprotein monooxygenases.
Int.J.Biol.Macromol., 328:147543-147543, 2025

PubMed Abstract: The reductase components of two-component flavoprotein monooxygenases (FPMOs) can reduce flavin mononucleotide (FMN) or flavin adenine dinucleotide (FAD) for their monooxygenase partners. Typically, the type of flavin cofactor bound by a flavoenzyme dictates the cofactor applied in its catalytic reactions. Here, we report the discovery of StnC, a previously unknown reductase family member involved in the biosynthesis of streptonigrin, a potent antimicrobial and antitumor compound. StnC exhibits a paradoxical performance in binding ability and catalytic activity toward flavins. Specifically, it binds FMN 147-fold stronger than FAD, but reduces FAD six times faster than FMN, enabling it to supply reduced FAD to its FAD-preferred monooxygenase partner StnD efficiently. Crystallographic, computational, and structural comparative analyses identified key residues and distinct structural features in StnC-like reductases, including extended clamp-like loops, that enable tight FMN binding and efficient FAD reduction. These features define a family of FAD-preferred reductases under physiological conditions. Our findings significantly broaden the understanding of the sequence-structure-function relationships in FPMO reductase components, uncover a structurally unique family of FAD-preferred reductases, and provide mechanistic insights into their coordination with monooxygenase partners.

PubMed: 40935041
DOI: 10.1016/j.ijbiomac.2025.147543

Experimental method

X-RAY DIFFRACTION (1.82 Å)