8FEK

Crystal structure of PBP cyclase Ulm16

8FEK の概要

• エントリーDOI: 10.2210/pdb8fek/pdb
• 分子名称: PBP cyclase Ulm16 (2 entities in total)
• 機能のキーワード: thioesterase, cyclase, heterochiral, ulleungmycin, hydrolase
• 由来する生物種: Streptomyces sp. KCB13F003
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 44758.66

構造登録者

Patel, R.,Budimir, Z.,Parkinson, E.,Das, C. (登録日: 2022-12-06, 公開日: 2023-11-08, 最終更新日: 2024-03-27)

主引用文献

Budimir, Z.L.,Patel, R.S.,Eggly, A.,Evans, C.N.,Rondon-Cordero, H.M.,Adams, J.J.,Das, C.,Parkinson, E.I.
Biocatalytic cyclization of small macrolactams by a penicillin-binding protein-type thioesterase.
Nat.Chem.Biol., 20:120-128, 2024

PubMed Abstract: Macrocyclic peptides represent promising scaffolds for chemical tools and potential therapeutics. Synthetic methods for peptide macrocyclization are often hampered by C-terminal epimerization and oligomerization, leading to difficult scalability. While chemical strategies to circumvent this issue exist, they often require specific amino acids to be present in the peptide sequence. Herein, we report the characterization of Ulm16, a peptide cyclase belonging to the penicillin-binding protein-type class of thioesterases that catalyze head-to-tail macrolactamization of nonribosmal peptides. Ulm16 efficiently cyclizes various nonnative peptides ranging from 4 to 6 amino acids with catalytic efficiencies of up to 3 × 10 M s. Unlike many previously described homologs, Ulm16 tolerates a variety of C- and N-terminal amino acids. The crystal structure of Ulm16, along with modeling of its substrates and site-directed mutagenesis, allows for rationalization of this wide substrate scope. Overall, Ulm16 represents a promising tool for the biocatalytic production of macrocyclic peptides.

PubMed: 38062262
DOI: 10.1038/s41589-023-01495-z

実験手法

X-RAY DIFFRACTION (2.058 Å)