PDBsum entry 2n6y

Ligase

PDB id: 2n6y

Contents

Protein chain

80 a.a.

PDB id:

2n6y

Name:

Ligase

Title:

Solution structure of holo arcp from yersiniabactin synthetase

Structure:

Hmwp2 nonribosomal peptide synthetase. Chain: a. Fragment: unp residues 14-93. Synonym: yersiniabactin biosynthetic protein. Engineered: yes

Source:

Yersinia pestis. Organism_taxid: 632. Gene: irp2, y2399, ypo1911. Expressed in: escherichia coli. Expression_system_taxid: 562.

NMR struc:

20 models

Authors:

A.C.Goodrich,B.J.Harden,D.P.Frueh

Key ref:

A.C.Goodrich et al. (2015). Solution Structure of a Nonribosomal Peptide Synthetase Carrier Protein Loaded with Its Substrate Reveals Transient, Well-Defined Contacts. J Am Chem Soc, 137, 12100-12109. PubMed id: 26334259 DOI: 10.1021/jacs.5b07772

Date:

31-Aug-15 Release date: 23-Sep-15

Protein chain

A0A2S9PH42  (A0A2S9PH42_YERPE) -  Yersiniabactin biosynthetic protein from Yersinia pestis

Seq: 2035 a.a.

Struc: 80 a.a.*

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

DOI no: 10.1021/jacs.5b07772

J Am Chem Soc 137:12100-12109 (2015)

PubMed id: 26334259

Solution Structure of a Nonribosomal Peptide Synthetase Carrier Protein Loaded with Its Substrate Reveals Transient, Well-Defined Contacts.

A.C.Goodrich, B.J.Harden, D.P.Frueh.

ABSTRACT

Nonribosomal peptide synthetases (NRPSs) are microbial enzymes that produce a wealth of important natural products by condensing substrates in an assembly line manner. The proper sequence of substrates is obtained by tethering them to phosphopantetheinyl arms of holo carrier proteins (CPs) via a thioester bond. CPs in holo and substrate-loaded forms visit NRPS catalytic domains in a series of transient interactions. A lack of structural information on substrate-loaded carrier proteins has hindered our understanding of NRPS synthesis. Here, we present the first structure of an NRPS aryl carrier protein loaded with its substrate via a native thioester bond, together with the structure of its holo form. We also present the first quantification of NRPS CP backbone dynamics. Our results indicate that prosthetic moieties in both holo and loaded forms are in contact with the protein core, but they also sample states in which they are disordered and extend in solution. We observe that substrate loading induces a large conformational change in the phosphopantetheinyl arm, thereby modulating surfaces accessible for binding to other domains. Our results are discussed in the context of NRPS domain interactions.