4JN5

Crystal structures of the first condensation domain of the CDA synthetase

4JN5 の概要

• エントリーDOI: 10.2210/pdb4jn5/pdb
• 関連するPDBエントリー: 4JN3
• 分子名称: CDA peptide synthetase I (2 entities in total)
• 機能のキーワード: nonribosomal peptide synthetase, nrps condensation domain, calcium-dependent antibiotic, biosynthetic protein, peptide bond formation, coa dependant acyltransferase superfamily
• 由来する生物種: Streptomyces coelicolor
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 97068.94

構造登録者

Bloudoff, K.,Schmeing, T.M. (登録日: 2013-03-14, 公開日: 2013-06-19, 最終更新日: 2024-02-28)

主引用文献

Bloudoff, K.,Rodionov, D.,Schmeing, T.M.
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, 2013

PubMed 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.

PubMed: 23756159
DOI: 10.1016/j.jmb.2013.06.003

実験手法

X-RAY DIFFRACTION (2.44 Å)