PDBsum entry 6e6t

Lyase/antibiotic

PDB id: 6e6t

Contents

Protein chains

266 a.a.

Ligands

SO4 ×2

HVV ×2

Waters ×374

PDB id:

6e6t

Name:

Lyase/antibiotic

Title:

Dieckmann cyclase, ncmc, bound to cerulenin

Structure:

Ncmc. Chain: a, b. Engineered: yes

Source:

Saccharothrix syringae. Organism_taxid: 103733. Atcc: 51364. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008

Resolution:

1.60Å R-factor: 0.189 R-free: 0.218

Authors:

D.P.Cogan,S.K.Nair

Key ref:

D.P.Cogan et al. (2020). Structural Basis for Enzymatic Off-Loading of Hybrid Polyketides by Dieckmann Condensation. ACS Chem Biol, 15, 2783-2791. PubMed id: 33017142 DOI: 10.1021/acschembio.0c00579

Date:

25-Jul-18 Release date: 31-Jul-19

Protein chains

A0A1X9WEN9  (A0A1X9WEN9_SACSY) -  NcmC from Saccharothrix syringae

Seq: 272 a.a.

Struc: 266 a.a.

DOI no: 10.1021/acschembio.0c00579

ACS Chem Biol 15:2783-2791 (2020)

PubMed id: 33017142

Structural Basis for Enzymatic Off-Loading of Hybrid Polyketides by Dieckmann Condensation.

D.P.Cogan, J.Ly, S.K.Nair.

ABSTRACT

While several bioactive natural products that contain tetramate or pyridone heterocycles have been described, information on the enzymology underpinning these functionalities has been limited. Here we biochemically characterize an off-loading Dieckmann cyclase, NcmC, that installs the tetramate headgroup in nocamycin, a hybrid polyketide/nonribosomal peptide natural product. Crystal structures of the enzyme (1.6 Å) and its covalent complex with the epoxide cerulenin (1.6 Å) guide additional structure-based mutagenesis and product-profile analyses. Our results offer mechanistic insights into how the conserved thioesterase-like scaffold has been adapted to perform a new chemical reaction, namely, heterocyclization. Additional bioinformatics combined with docking and modeling identifies likely candidates for heterocycle formation in underexplored gene clusters and uncovers a modular basis of substrate recognition by the two subdomains of these Dieckmann cyclases.