8W2C

Thioesterase domain structure from Sulfazecin biosynthetic nonribosomal peptide synthetase SulM

8W2C の概要

• エントリーDOI: 10.2210/pdb8w2c/pdb
• 分子名称: Non-ribosomal peptide synthetase, 1,2-ETHANEDIOL, SODIUM ION, ... (4 entities in total)
• 機能のキーワード: thioesterase domain, nrps, nonribosomal peptide synthetase, sulfazecin, hydrolase
• 由来する生物種: Paraburkholderia acidicola
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 61270.47

構造登録者

Patel, K.D.,Gulick, A.M. (登録日: 2024-02-20, 公開日: 2024-08-07, 最終更新日: 2024-09-18)

主引用文献

Patel, K.D.,Oliver, R.A.,Lichstrahl, M.S.,Li, R.,Townsend, C.A.,Gulick, A.M.
The structure of the monobactam-producing thioesterase domain of SulM forms a unique complex with the upstream carrier protein domain.
J.Biol.Chem., 300:107489-107489, 2024

PubMed Abstract: Nonribosomal peptide synthetases (NRPSs) are responsible for the production of important biologically active peptides. The large, multidomain NRPSs operate through an assembly line strategy in which the growing peptide is tethered to carrier domains that deliver the intermediates to neighboring catalytic domains. While most NRPS domains catalyze standard chemistry of amino acid activation, peptide bond formation, and product release, some canonical NRPS catalytic domains promote unexpected chemistry. The paradigm monobactam antibiotic sulfazecin is produced through the activity of a terminal thioesterase domain of SulM, which catalyzes an unusual β-lactam-forming reaction in which the nitrogen of the C-terminal N-sulfo-2,3-diaminopropionate residue attacks its thioester tether to release the monobactam product. We have determined the structure of the thioesterase domain as both a free-standing domain and a didomain complex with the upstream holo peptidyl-carrier domain. The position of variant lid helices results in an active site pocket that is quite constrained, a feature that is likely necessary to orient the substrate properly for β-lactam formation. Modeling of a sulfazecin tripeptide into the active site identifies a plausible binding mode identifying potential interactions for the sulfamate and the peptide backbone with Arg2849 and Asn2819, respectively. The overall structure is similar to the β-lactone-forming thioesterase domain that is responsible for similar ring closure in the production of obafluorin. We further use these insights to enable bioinformatic analysis to identify additional, uncharacterized β-lactam-forming biosynthetic gene clusters by genome mining.

PubMed: 38908753
DOI: 10.1016/j.jbc.2024.107489

実験手法

X-RAY DIFFRACTION (1.9 Å)