5JQF

Crystal structure of the lasso peptide Sphingopyxin I (SpI)

5JQF の概要

• エントリーDOI: 10.2210/pdb5jqf/pdb
• 関連するPDBエントリー: 5JRK 5JRL
• 分子名称: Sphingopyxin I (2 entities in total)
• 機能のキーワード: lasso peptide, isopeptide bond, macrolactam ring, unknown function
• 由来する生物種: Sphingopyxis alaskensis RB2256
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 4402.65

構造登録者

Fage, C.D.,Hegemann, J.D.,Harms, K.,Bange, G.,Marahiel, M.A. (登録日: 2016-05-04, 公開日: 2016-09-14, 最終更新日: 2024-10-23)

主引用文献

Fage, C.D.,Hegemann, J.D.,Nebel, A.J.,Steinbach, R.M.,Zhu, S.,Linne, U.,Harms, K.,Bange, G.,Marahiel, M.A.
Structure and Mechanism of the Sphingopyxin I Lasso Peptide Isopeptidase.
Angew. Chem. Int. Ed. Engl., 55:12717-12721, 2016

PubMed Abstract: Lasso peptides are natural products that assume a unique lariat knot topology. Lasso peptide isopeptidases (IsoPs) eliminate this topology through isopeptide bond cleavage. To probe how these enzymes distinguish between substrates and hydrolyze only isopeptide bonds, we examined the structure and mechanism of a previously uncharacterized IsoP from the proteobacterium Sphingopyxis alaskensis RB2256 (SpI-IsoP). We demonstrate that SpI-IsoP efficiently and specifically linearizes the lasso peptide sphingopyxin I (SpI) and variants thereof. We also present crystal structures of SpI and SpI-IsoP, revealing a threaded topology for the former and a prolyl oligopeptidase (POP)-like fold for the latter. Subsequent structure-guided mutational analysis allowed us to propose roles for active-site residues. Our study sheds light on lasso peptide catabolism and expands the engineering potential of these fascinating molecules.

PubMed: 27611791
DOI: 10.1002/anie.201605232

実験手法

X-RAY DIFFRACTION (0.85 Å)