4D4H

Understanding bi-specificity of A-domains

4D4H の概要

• エントリーDOI: 10.2210/pdb4d4h/pdb
• 関連するPDBエントリー: 4D4G 4D4I 4D56 4D57
• 分子名称: APNAA1, GLYCEROL (3 entities in total)
• 機能のキーワード: hydrolase, non-ribosomal peptide synthetase, adenylation, a domain
• 由来する生物種: Planktothrix agardhii
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 64682.48

構造登録者

Kaljunen, H.,Schiefelbein, S.H.H.,Stummer, D.,Kozak, S.,Meijers, R.,Christiansen, G.,Rentmeister, A. (登録日: 2014-10-29, 公開日: 2015-07-01, 最終更新日: 2023-12-20)

主引用文献

Kaljunen, H.,Schiefelbein, S.H.H.,Stummer, D.,Kozak, S.,Meijers, R.,Christiansen, G.,Rentmeister, A.
Structural Elucidation of the Bispecificity of a Domains as a Basis for Activating Non-Natural Amino Acids.
Angew.Chem.Int.Ed.Engl., 54:8833-, 2015

PubMed Abstract: Many biologically active peptide secondary metabolites of bacteria are produced by modular enzyme complexes, the non-ribosomal peptide synthetases. Substrate selection occurs through an adenylation (A) domain, which activates the cognate amino acid with high fidelity. The recently discovered A domain of an Anabaenopeptin synthetase from Planktothrix agardhii (ApnA A1) is capable of activating two chemically distinct amino acids (Arg and Tyr). Crystal structures of the A domain reveal how both substrates fit into to binding pocket of the enzyme. Analysis of the binding pocket led to the identification of three residues that are critical for substrate recognition. Systematic mutagenesis of these residues created A domains that were monospecific, or changed the substrate specificity to tryptophan. The non-natural amino acid 4-azidophenylalanine is also efficiently activated by a mutant A domain, thus enabling the production of diversified non-ribosomal peptides for bioorthogonal labeling.

PubMed: 26096082
DOI: 10.1002/ANGE.201503275

実験手法

X-RAY DIFFRACTION (2.019 Å)