PDBsum entry 4jn3

Biosynthetic protein

PDB id: 4jn3

Contents

Protein chains

446 a.a.

Waters ×1275

PDB id:

4jn3

Name:

Biosynthetic protein

Title:

Crystal structures of the first condensation domain of the cda synthetase

Structure:

Cda peptide synthetase i. Chain: a, b. Fragment: first condensation domain. Engineered: yes

Source:

Streptomyces coelicolor. Organism_taxid: 100226. Strain: atcc baa-471 / a3(2) / m145. Gene: sco3230. Expressed in: escherichia coli. Expression_system_taxid: 562

Resolution:

1.69Å R-factor: 0.193 R-free: 0.212

Authors:

K.Bloudoff,T.M.Schmeing

Key ref:

K.Bloudoff et al. (2013). Crystal structures of the first condensation domain of CDA synthetase suggest conformational changes during the synthetic cycle of nonribosomal peptide synthetases. J Mol Biol, 425, 3137-3150. PubMed id: 23756159 DOI: 10.1016/j.jmb.2013.06.003

Date:

14-Mar-13 Release date: 19-Jun-13

Protein chains

Q9Z4X6  (Q9Z4X6_STRCO) -  CDA peptide synthetase I from Streptomyces coelicolor (strain ATCC BAA-471 / A3(2) / M145)

Seq: 7463 a.a.

Struc: 446 a.a.

DOI no: 10.1016/j.jmb.2013.06.003

J Mol Biol 425:3137-3150 (2013)

PubMed id: 23756159

Crystal structures of the first condensation domain of CDA synthetase suggest conformational changes during the synthetic cycle of nonribosomal peptide synthetases.

K.Bloudoff, D.Rodionov, T.M.Schmeing.

ABSTRACT

Nonribosomal peptide synthetases (NRPSs) are large modular macromolecular machines that produce small peptide molecules with wide-ranging biological activities, such as antibiotics and green chemicals. The condensation (C) domain is responsible for amide bond formation, the central chemical step in nonribosomal peptide synthesis. Here we present two crystal structures of the first condensation domain of the calcium-dependent antibiotic (CDA) synthetase (CDA-C1) from Streptomyces coelicolor, determined at resolutions 1.8Å and 2.4Å. The conformations adopted by CDA-C1 are quite similar in these two structures yet distinct from those seen in other NRPS C domain structures. HPLC-based reaction assays show that this CDA-C1 construct is catalytically active, and small-angle X-ray scattering experiments suggest that the conformation observed in these crystal structures could faithfully represent the conformation in solution. We have performed targeted molecular dynamics simulations, normal mode analyses and energy-minimized linear interpolation to investigate the conformational changes required to transition between the observed structures. We discuss the implications of these conformational changes in the synthetic cycle and of the observation that the "latch" that covers the active site is consistently formed in all studied C domains.