8SMS

Crosslinked Crystal Structure of Type II Fatty Acid Synthase, FabB, and cerulenin crosslinker-crypto Acyl Carrier Protein, AcpP

Summary for 8SMS

• Entry DOI: 10.2210/pdb8sms/pdb
• Descriptor: 3-oxoacyl-[acyl-carrier-protein] synthase 1, Acyl carrier protein, N~3~-[(2R)-2-hydroxy-3,3-dimethyl-4-(phosphonooxy)butanoyl]-N-{2-[(2R)-2-hydroxy-4-oxododecanamido]ethyl}-beta-alaninamide, ... (4 entities in total)
• Functional Keywords: ketosynthase, fabb, acpp, acyl carrier protein, cerulenin, crosslinker, crosslink, fatty acid biosynthesis, natural product, biosynthetic protein
• Biological source: Escherichia coli K-12; More
• Total number of polymer chains: 4
• Total formula weight: 103327.95

Authors

Jiang, Z.,Chen, A.,Chen, J.,Sekhon, A.,Louie, G.V.,Noel, J.P.,La Clair, J.J.,Burkart, M.D. (deposition date: 2023-04-26, release date: 2023-09-27, Last modification date: 2024-10-23)

Primary citation

Jiang, Z.,Chen, A.,Chen, J.,Sekhon, A.,Louie, G.V.,Noel, J.P.,La Clair, J.J.,Burkart, M.D.
Masked cerulenin enables a dual-site selective protein crosslink.
Chem Sci, 14:10925-10933, 2023

PubMed Abstract: Protein-reactive natural products such as the fungal metabolite cerulenin are recognized for their value as therapeutic candidates, due to their ability to selectively react with catalytic residues within a protein active site or a complex of protein domains. Here, we explore the development of fatty-acid and polyketide-synthase probes by synthetically modulating cerulenin's functional moieties. Using a mechanism-based approach, we reveal unique reactivity within cerulenin and adapt it for fluorescent labeling and crosslinking of fatty-acid and iterative type-I polyketide synthases. We also describe two new classes of silylcyanohydrin and silylhemiaminal masked crosslinking probes that serve as new tools for activity and structure studies of these biosynthetic pathways.

PubMed: 37829009
DOI: 10.1039/d3sc02864j

Experimental method

X-RAY DIFFRACTION (1.93 Å)