PDBsum entry 5es6

Ligase

PDB id: 5es6

Contents

Protein chain

583 a.a.

Ligands

FMT ×3

Waters ×66

PDB id:

5es6

Name:

Ligase

Title:

Crystal structure of the first two domains of the initiation module of lgra

Structure:

Linear gramicidin synthase subunit a. Chain: a. Fragment: unp residues 2-584. Engineered: yes

Source:

Brevibacillus parabrevis. Organism_taxid: 54914. Gene: lgra. Expressed in: escherichia coli. Expression_system_taxid: 562

Resolution:

2.46Å R-factor: 0.224 R-free: 0.251

Authors:

J.M.Reimer,M.N.Aloise,T.M.Schmeing

Key ref:

J.M.Reimer et al. (2016). Synthetic cycle of the initiation module of a formylating nonribosomal peptide synthetase. Nature, 529, 239-242. PubMed id: 26762462 DOI: 10.1038/nature16503

Date:

16-Nov-15 Release date: 20-Jan-16

Protein chain

Q70LM7  (LGRA_BREPA) -  Linear gramicidin synthase subunit A from Brevibacillus parabrevis

Seq: 2273 a.a.

Struc: 583 a.a.*

* PDB and UniProt seqs differ at 1 residue position (black cross)

DOI no: 10.1038/nature16503

Nature 529:239-242 (2016)

PubMed id: 26762462

Synthetic cycle of the initiation module of a formylating nonribosomal peptide synthetase.

J.M.Reimer, M.N.Aloise, P.M.Harrison, T.M.Schmeing.

ABSTRACT

Nonribosomal peptide synthetases (NRPSs) are very large proteins that produce small peptide molecules with wide-ranging biological activities, including environmentally friendly chemicals and many widely used therapeutics. NRPSs are macromolecular machines, with modular assembly-line logic, a complex catalytic cycle, moving parts and many active sites. In addition to the core domains required to link the substrates, they often include specialized tailoring domains, which introduce chemical modifications and allow the product to access a large expanse of chemical space. It is still unknown how the NRPS tailoring domains are structurally accommodated into megaenzymes or how they have adapted to function in nonribosomal peptide synthesis. Here we present a series of crystal structures of the initiation module of an antibiotic-producing NRPS, linear gramicidin synthetase. This module includes the specialized tailoring formylation domain, and states are captured that represent every major step of the assembly-line synthesis in the initiation module. The transitions between conformations are large in scale, with both the peptidyl carrier protein domain and the adenylation subdomain undergoing huge movements to transport substrate between distal active sites. The structures highlight the great versatility of NRPSs, as small domains repurpose and recycle their limited interfaces to interact with their various binding partners. Understanding tailoring domains is important if NRPSs are to be utilized in the production of novel therapeutics.