PDBsum entry 4zxi

Biosynthetic protein

PDB id: 4zxi

Contents

Protein chain

1314 a.a.

Ligands

PNS

GLY

AMP

XP4

Metals

_MG

_NI

Waters ×16

PDB id:

4zxi

Name:

Biosynthetic protein

Title:

Crystal structure of holo-ab3403 a four domain nonribosomal peptide synthetase bound to amp and glycine

Structure:

Tyrocidine synthetase 3. Chain: a. Engineered: yes

Source:

Acinetobacter baumannii (strain ab307-0294). Organism_taxid: 557600. Strain: ab307-0294. Gene: abbfa_003403. Expressed in: escherichia coli. Expression_system_taxid: 469008.

Resolution:

2.90Å R-factor: 0.176 R-free: 0.225

Authors:

E.J.Drake,B.R.Miller,C.L.Allen,A.M.Gulick

Key ref:

E.J.Drake et al. (2016). Structures of two distinct conformations of holo-non-ribosomal peptide synthetases. Nature, 529, 235-238. PubMed id: 26762461 DOI: 10.1038/nature16163

Date:

20-May-15 Release date: 30-Dec-15

Protein chain

A0A0X1KH98  (A0A0X1KH98_ACIB3) -  Abbfa_003403 from Acinetobacter baumannii (strain AB307-0294)

Seq: 1320 a.a.

Struc: 1314 a.a.

DOI no: 10.1038/nature16163

Nature 529:235-238 (2016)

PubMed id: 26762461

Structures of two distinct conformations of holo-non-ribosomal peptide synthetases.

E.J.Drake, B.R.Miller, C.Shi, J.T.Tarrasch, J.A.Sundlov, C.L.Allen, G.Skiniotis, C.C.Aldrich, A.M.Gulick.

ABSTRACT

Many important natural products are produced by multidomain non-ribosomal peptide synthetases (NRPSs). During synthesis, intermediates are covalently bound to integrated carrier domains and transported to neighbouring catalytic domains in an assembly line fashion. Understanding the structural basis for catalysis with non-ribosomal peptide synthetases will facilitate bioengineering to create novel products. Here we describe the structures of two different holo-non-ribosomal peptide synthetase modules, each revealing a distinct step in the catalytic cycle. One structure depicts the carrier domain cofactor bound to the peptide bond-forming condensation domain, whereas a second structure captures the installation of the amino acid onto the cofactor within the adenylation domain. These structures demonstrate that a conformational change within the adenylation domain guides transfer of intermediates between domains. Furthermore, one structure shows that the condensation and adenylation domains simultaneously adopt their catalytic conformations, increasing the overall efficiency in a revised structural cycle. These structures and the single-particle electron microscopy analysis demonstrate a highly dynamic domain architecture and provide the foundation for understanding the structural mechanisms that could enable engineering of novel non-ribosomal peptide synthetases.