5DUA

First condensation domain of the calcium-dependent antibiotic synthetase in complex with substrate analogue 3a

5DUA の概要

• エントリーDOI: 10.2210/pdb5dua/pdb
• 関連するPDBエントリー: 5DU9
• 分子名称: CDA peptide synthetase I, N-pentyl-L-alaninamide, CHLORIDE ION, ... (4 entities in total)
• 機能のキーワード: nonribosomal peptide synthetase, condensation domain, chemical probe, substrate analogue, phosphopantetheine binding protein
• 由来する生物種: Streptomyces coelicolor (strain ATCC BAA-471 / A3(2) / M145)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 97368.93

構造登録者

Bloudoff, K.,Alonzo, D.A.,Schmeing, T.M. (登録日: 2015-09-18, 公開日: 2016-03-30, 最終更新日: 2024-11-13)

主引用文献

Bloudoff, K.,Alonzo, D.A.,Schmeing, T.M.
Chemical Probes Allow Structural Insight into the Condensation Reaction of Nonribosomal Peptide Synthetases.
Cell Chem Biol, 23:331-339, 2016

PubMed Abstract: Nonribosomal peptide synthetases (NRPSs) synthesize a vast variety of small molecules, including antibiotics, antitumors, and immunosuppressants. The NRPS condensation (C) domain catalyzes amide bond formation, the central chemical step in nonribosomal peptide synthesis. The catalytic mechanism and substrate determinants of the reaction are under debate. We developed chemical probes to structurally study the NRPS condensation reaction. These substrate analogs become covalently tethered to a cysteine introduced near the active site, to mimic covalent substrate delivery by carrier domains. They are competent substrates in the condensation reaction and behave similarly to native substrates. Co-crystal structures show C domain-substrate interactions, and suggest that the catalytic histidine's principle role is to position the α-amino group for nucleophilic attack. Structural insight provided by these co-complexes also allowed us to alter the substrate specificity profile of the reaction with a single point mutation.

PubMed: 26991102
DOI: 10.1016/j.chembiol.2016.02.012

実験手法

X-RAY DIFFRACTION (1.9 Å)