4ZA1

Crystal Structure of NosA Involved in Nosiheptide Biosynthesis

4ZA1 の概要

• エントリーDOI: 10.2210/pdb4za1/pdb
• 分子名称: NosA, 2,3-DIHYDROXY-1,4-DITHIOBUTANE (3 entities in total)
• 機能のキーワード: beta barrel, transferase
• 由来する生物種: Streptomyces actuosus
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 49060.95

構造登録者

Liu, S.,Guo, H.,Zhang, T.,Han, L.,Yao, P.,Zhang, Y.,Rong, N.,Yu, Y.,Lan, W.,Wang, C.,Ding, J.,Wang, R.,Liu, W.,Cao, C. (登録日: 2015-04-13, 公開日: 2015-08-19, 最終更新日: 2024-03-20)

主引用文献

Liu, S.,Guo, H.,Zhang, T.,Han, L.,Yao, P.,Zhang, Y.,Rong, N.,Yu, Y.,Lan, W.,Wang, C.,Ding, J.,Wang, R.,Liu, W.,Cao, C.
Structure-based Mechanistic Insights into Terminal Amide Synthase in Nosiheptide-Represented Thiopeptides Biosynthesis
Sci Rep, 5:12744-12744, 2015

PubMed Abstract: Nosiheptide is a parent compound of thiopeptide family that exhibit potent activities against various bacterial pathogens. Its C-terminal amide formation is catalyzed by NosA, which is an unusual strategy for maturating certain thiopeptides by processing their precursor peptides featuring a serine extension. We here report the crystal structure of truncated NosA1-111 variant, revealing three key elements, including basic lysine 49 (K49), acidic glutamic acid 101 (E101) and flexible C-terminal loop NosA112-151, are crucial to the catalytic terminal amide formation in nosiheptide biosynthesis. The side-chain of residue K49 and the C-terminal loop fasten the substrate through hydrogen bonds and hydrophobic interactions. The side-chain of residue E101 enhances nucleophilic attack of H2O to the methyl imine intermediate, leading to Cα-N bond cleavage and nosiheptide maturation. The sequence alignment of NosA and its homologs NocA, PbtH, TpdK and BerI, and the enzymatic assay suggest that the mechanistic studies on NosA present an intriguing paradigm about how NosA family members function during thiopeptide biosynthesis.

PubMed: 26244829
DOI: 10.1038/srep12744

実験手法

X-RAY DIFFRACTION (2.5 Å)