9UPQ

Structure of 3-amino-3-carboxyltransferase

Summary for 9UPQ

• Entry DOI: 10.2210/pdb9upq/pdb
• Descriptor: Isonocardicin synthase, CHLORIDE ION (3 entities in total)
• Functional Keywords: 3-amino-3-carboxyltransferase, nocardicin, biosynthesis, transferase
• Biological source: Nocardia uniformis subsp. tsuyamanensis
• Total number of polymer chains: 2
• Total formula weight: 71071.24

Authors

Gao, Y.,Mori, T.,Awakawa, T.,Abe, I. (deposition date: 2025-04-28, release date: 2026-04-29)

Primary citation

Gao, Y.,Karasawa, M.,Quan, Z.,Mori, T.,Kanaida, M.,Townsend, C.A.,Terada, T.,Abe, I.,Awakawa, T.
Structural Basis for 3-Amino-3-carboxypropyl Transfer in Nocardicin Biosynthesis.
J.Am.Chem.Soc., 147:33589-33596, 2025

PubMed Abstract: -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 β-lactam antibiotic nocardicin G () 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 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 Cα-amino group of SAM functions as a Brønsted base to enhance the nucleophilicity of the C6'-OH of , with the assistance of E143, thereby facilitating S2 attack on the Cγ of SAM. This study presents structural and computational analysis leading to more precise understanding of 3-ACP transfer.

PubMed: 40921178
DOI: 10.1021/jacs.5c08367

Experimental method

X-RAY DIFFRACTION (1.75 Å)