8K3X

S. cerevisiae Chs1 in complex with Nikkomycin Z

Summary for 8K3X

• Entry DOI: 10.2210/pdb8k3x/pdb
• EMDB information: 36864
• Descriptor: Chitin synthase 1, (2S)-{[(2S,3S,4S)-2-amino-4-hydroxy-4-(5-hydroxypyridin-2-yl)-3-methylbutanoyl]amino}[(2R,3S,4R,5R)-5-(2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)-3,4-dihydroxyoxolan-2-yl]acetic acid (non-preferred name) (2 entities in total)
• Functional Keywords: antifungal protein-inhibitor complex, antifungal protein/inhibitor
• Biological source: Saccharomyces cerevisiae (baker's yeast)
• Total number of polymer chains: 2
• Total formula weight: 260993.16

Authors

Bai, L.,Chen, D. (deposition date: 2023-07-17, release date: 2023-10-18, Last modification date: 2024-05-08)

Primary citation

Chen, D.D.,Wang, Z.B.,Wang, L.X.,Zhao, P.,Yun, C.H.,Bai, L.
Structure, catalysis, chitin transport, and selective inhibition of chitin synthase.
Nat Commun, 14:4776-4776, 2023

PubMed Abstract: Chitin is one of the most abundant natural biopolymers and serves as a critical structural component of extracellular matrices, including fungal cell walls and insect exoskeletons. As a linear polymer of β-(1,4)-linked N-acetylglucosamine, chitin is synthesized by chitin synthases, which are recognized as targets for antifungal and anti-insect drugs. In this study, we determine seven different cryo-electron microscopy structures of a Saccharomyces cerevisiae chitin synthase in the absence and presence of glycosyl donor, acceptor, product, or peptidyl nucleoside inhibitors. Combined with functional analyses, these structures show how the donor and acceptor substrates bind in the active site, how substrate hydrolysis drives self-priming, how a chitin-conducting transmembrane channel opens, and how peptidyl nucleoside inhibitors inhibit chitin synthase. Our work provides a structural basis for understanding the function and inhibition of chitin synthase.

PubMed: 37553334
DOI: 10.1038/s41467-023-40479-4

Experimental method

ELECTRON MICROSCOPY (2.86 Å)