8SAP

Crystal structure of class III lanthipeptide synthetase ThurKC

8SAP の概要

• エントリーDOI: 10.2210/pdb8sap/pdb
• 分子名称: Class III lanthionine synthetase LanKC (2 entities in total)
• 機能のキーワード: lanthipeptide, synthetase, kinase, lyase, cyclase, complex, class iii, ripp, natural product, transferase, bacterial, labionin, biosynthetic protein
• 由来する生物種: Bacillus thuringiensis serovar andalousiensis
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 200037.73

構造登録者

Hernandez Garcia, A.,Nair, S.K. (登録日: 2023-04-01, 公開日: 2023-10-11, 最終更新日: 2023-11-08)

主引用文献

Hernandez Garcia, A.,Nair, S.K.
Structure and Function of a Class III Metal-Independent Lanthipeptide Synthetase.
Acs Cent.Sci., 9:1944-1956, 2023

PubMed Abstract: In bacteria, Ser/Thr protein kinase-like sequences are found as part of large multidomain polypeptides that biosynthesize lanthipeptides, a class of natural products distinguished by the presence of thioether cross-links. The kinase domain phosphorylates Ser or Thr residues in the peptide substrates. Subsequent β-elimination by a lyase domain yields electrophilic dehydroamino acids, which can undergo cyclase domain-catalyzed cyclization to yield conformationally restricted, bioactive compounds. Here, we reconstitute the biosynthetic pathway for a class III lanthipeptide from NRRL B-23139, including characterization of a two-component protease for leader peptide excision. We also describe the first crystal structures of a class III lanthipeptide synthetase, consisting of the lyase, kinase, and cyclase domains, in various states including complexes with its leader peptide and nucleotide. The structure shows interactions between all three domains that result in an active conformation of the kinase domain. Biochemical analysis demonstrates that the three domains undergo movement upon binding of the leader peptide to establish interdomain allosteric interactions that stabilize this active form. These studies inform on the regulatory mechanism of substrate recognition and provide a framework for engineering of variants of biotechnological interest.

PubMed: 37901177
DOI: 10.1021/acscentsci.3c00484

実験手法

X-RAY DIFFRACTION (2.52 Å)