8FEK

Crystal structure of PBP cyclase Ulm16

Summary for 8FEK

• Entry DOI: 10.2210/pdb8fek/pdb
• Descriptor: PBP cyclase Ulm16 (2 entities in total)
• Functional Keywords: thioesterase, cyclase, heterochiral, ulleungmycin, hydrolase
• Biological source: Streptomyces sp. KCB13F003
• Total number of polymer chains: 1
• Total formula weight: 44758.66

Authors

Patel, R.,Budimir, Z.,Parkinson, E.,Das, C. (deposition date: 2022-12-06, release date: 2023-11-08, Last modification date: 2024-03-27)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (2.058 Å)