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Crosslinked Crystal Structure of Type II Fatty Acid Synthase, FabB, and cerulenin crosslinker-crypto Acyl Carrier Protein, AcpPCrosslinked Crystal Structure of Type II Fatty Acid Synthase, FabB, and cerulenin crosslinker-crypto Acyl Carrier Protein, AcpP
Structural highlights
FunctionFABB_ECOLI Catalyzes the condensation reaction of fatty acid synthesis by the addition to an acyl acceptor of two carbons from malonyl-ACP. Specific for elongation from C-10 to unsaturated C-16 and C-18 fatty acids. Publication Abstract from PubMedProtein-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. Masked cerulenin enables a dual-site selective protein crosslink.,Jiang Z, Chen A, Chen J, Sekhon A, Louie GV, Noel JP, La Clair JJ, Burkart MD Chem Sci. 2023 Sep 8;14(39):10925-10933. doi: 10.1039/d3sc02864j. eCollection , 2023 Oct 11. PMID:37829009[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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