8T3P

Crystal structure of MonC1 (a flavin-dependent monooxygenase)

Summary for 8T3P

• Entry DOI: 10.2210/pdb8t3p/pdb
• Descriptor: MonCI, FLAVIN-ADENINE DINUCLEOTIDE, CHLORIDE ION, ... (4 entities in total)
• Functional Keywords: monc1, flavin-dependent monooxygenase, oxidoreductase
• Biological source: Streptomyces virginiae
• Total number of polymer chains: 2
• Total formula weight: 112148.61

Authors

Wang, Q.,Mathews, I.I.,Kim, C.Y. (deposition date: 2023-06-07, release date: 2023-11-08)

Primary citation

Wang, Q.,Liu, N.,Deng, Y.,Guan, Y.,Xiao, H.,Nitka, T.A.,Yang, H.,Yadav, A.,Vukovic, L.,Mathews, I.I.,Chen, X.,Kim, C.Y.
Triepoxide formation by a flavin-dependent monooxygenase in monensin biosynthesis.
Nat Commun, 14:6273-6273, 2023

PubMed Abstract: Monensin A is a prototypical natural polyether polyketide antibiotic. It acts by binding a metal cation and facilitating its transport across the cell membrane. Biosynthesis of monensin A involves construction of a polyene polyketide backbone, subsequent epoxidation of the alkenes, and, lastly, formation of cyclic ethers via epoxide-opening cyclization. MonCI, a flavin-dependent monooxygenase, is thought to transform all three alkenes in the intermediate polyketide premonensin A into epoxides. Our crystallographic study has revealed that MonCI's exquisite stereocontrol is due to the preorganization of the active site residues which allows only one specific face of the alkene to approach the reactive C(4a)-hydroperoxyflavin moiety. Furthermore, MonCI has an unusually large substrate-binding cavity that can accommodate premonensin A in an extended or folded conformation which allows any of the three alkenes to be placed next to C(4a)-hydroperoxyflavin. MonCI, with its ability to perform multiple epoxidations on the same substrate in a stereospecific manner, demonstrates the extraordinary versatility of the flavin-dependent monooxygenase family of enzymes.

PubMed: 37805629
DOI: 10.1038/s41467-023-41889-0

Experimental method

X-RAY DIFFRACTION (1.9 Å)