5MY0

KS-MAT DI-DOMAIN OF MOUSE FAS WITH MALONYL-COA

Summary for 5MY0

• Entry DOI: 10.2210/pdb5my0/pdb
• Descriptor: Fatty acid synthase, COENZYME A, MALONYL-COENZYME A, ... (4 entities in total)
• Functional Keywords: mouse fatty-acid-synthase ks-mat malonyl-coa, transferase
• Biological source: Mus musculus (Mouse); More
• Total number of polymer chains: 4
• Total formula weight: 371301.02

Authors

Paithankar, K.S.,Rittner, A.,Huu, K.V.,Grininger, M. (deposition date: 2017-01-25, release date: 2018-01-24, Last modification date: 2024-01-17)

Primary citation

Rittner, A.,Paithankar, K.S.,Huu, K.V.,Grininger, M.
Characterization of the Polyspecific Transferase of Murine Type I Fatty Acid Synthase (FAS) and Implications for Polyketide Synthase (PKS) Engineering.
ACS Chem. Biol., 13:723-732, 2018

PubMed Abstract: Fatty 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 β-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.

PubMed: 29328619
DOI: 10.1021/acschembio.7b00718

Experimental method

X-RAY DIFFRACTION (2.94 Å)