5my0
KS-MAT DI-DOMAIN OF MOUSE FAS WITH MALONYL-COAKS-MAT DI-DOMAIN OF MOUSE FAS WITH MALONYL-COA
Structural highlights
FunctionFAS_MOUSE Fatty acid synthetase catalyzes the formation of long-chain fatty acids from acetyl-CoA, malonyl-CoA and NADPH. This multifunctional protein has 7 catalytic activities and an acyl carrier protein. Publication Abstract from PubMedFatty acid synthases (FASs) and polyketide synthases (PKSs) condense acyl compounds to fatty acids and polyketides, respectively. Both, FASs and PKSs, harbor acyltransferases (ATs), which select substrates for condensation by beta-ketoacyl synthases (KSs). Here, we present the structural and functional characterization of the polyspecific malonyl/acetyltransferase (MAT) of murine FAS. We assign kinetic constants for the transacylation of the native substrates, acetyl- and malonyl-CoA, and demonstrate the promiscuity of FAS to accept structurally and chemically diverse CoA-esters. X-ray structural data of the KS-MAT didomain in a malonyl-loaded state suggests a MAT-specific role of an active site arginine in transacylation. Owing to its enzymatic properties and its accessibility as a separate domain, MAT of murine FAS may serve as versatile tool for engineering PKSs to provide custom-tailored access to new polyketides that can be applied in antibiotic and antineoplastic therapy. Characterization of the polyspecific transferase of murine type I fatty acid synthase (FAS) and implications for polyketide synthase (PKS) engineering.,Rittner A, Paithankar KS, Vu Huu K, Grininger M ACS Chem Biol. 2018 Jan 12. doi: 10.1021/acschembio.7b00718. PMID:29328619[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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