9upq
Structure of 3-amino-3-carboxyltransferase
Structural highlights
FunctionNAT_NOCUT Involved in the biosynthesis of the beta-lactam antibiotic nocardicin A (PubMed:9804844). In the presence of S-adenosyl-L-methionine (AdoMet), catalyzes the transfer of a 3-amino-3-carboxypropyl group from AdoMet to nocardicin G, forming isonocardicin C (PubMed:9804844). Can also catalyze the transformation of nocardicin E and F to isonocardicin A and B, respectively, but in vivo substrate is probably nocardicin G (PubMed:9804844).[1] Publication Abstract from PubMedS-Adenosyl-l-methionine (SAM) is well-known as a methyl donor for methyltransferases but also functions as a 3-amino-3-carboxypropyl (3-ACP) donor for 3-ACP transferases. NAT is a 3-ACP transferase which accepts beta-lactam antibiotic nocardicin G (1) and SAM to produce isonocardicin C. Due to the lack of structural information about this enzyme, its reaction mechanism has not been fully identified. In this study, we report two X-ray crystal structures of NAT, including its apo and complex structure with 1 and SAH. Examination of them identified the structural basis for substrate recognition. Comprehensive approach integrating site-directed mutagenesis, thermal shift assay, MD simulation, and QM/MM calculation revealed that the Calpha-amino group of SAM functions as a Bronsted base to enhance the nucleophilicity of the C6'-OH of 1, with the assistance of E143, thereby facilitating S(N)2 attack on the Cgamma of SAM. This study presents structural and computational analysis leading to more precise understanding of 3-ACP transfer. Structural Basis for 3-Amino-3-carboxypropyl Transfer in Nocardicin Biosynthesis.,Gao Y, Karasawa M, Quan Z, Mori T, Kanaida M, Townsend CA, Terada T, Abe I, Awakawa T J Am Chem Soc. 2025 Sep 17;147(37):33589-33596. doi: 10.1021/jacs.5c08367. Epub , 2025 Sep 8. PMID:40921178[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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