6NOX

Solution structure of SFTI-KLK5 inhibitor

6NOX の概要

• エントリーDOI: 10.2210/pdb6nox/pdb
• NMR情報: BMRB: 30562
• 分子名称: SFTI-KLK5 Peptide (1 entity in total)
• 機能のキーワード: protease inhibitor, biosynthetic protein
• 由来する生物種: Helianthus annuus
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 1694.89

構造登録者

White, A.M. (登録日: 2019-01-16, 公開日: 2019-04-03, 最終更新日: 2024-11-20)

主引用文献

Li, C.Y.,de Veer, S.J.,White, A.M.,Chen, X.,Harris, J.M.,Swedberg, J.E.,Craik, D.J.
Amino Acid Scanning at P5' within the Bowman-Birk Inhibitory Loop Reveals Specificity Trends for Diverse Serine Proteases.
J. Med. Chem., 62:3696-3706, 2019

PubMed Abstract: Sunflower trypsin inhibitor-1 (SFTI-1) is a 14-amino acid cyclic peptide that shares an inhibitory loop with a sequence and structure similar to a larger family of serine protease inhibitors, the Bowman-Birk inhibitors. Here, we focus on the P5' residue in the Bowman-Birk inhibitory loop and produce a library of SFTI variants to characterize the P5' specificity of 11 different proteases. We identify seven amino acids that are generally preferred by these enzymes and also correlate with P5' sequence diversity in naturally occurring Bowman-Birk inhibitors. Additionally, we show that several enzymes have divergent specificities that can be harnessed in engineering studies. By optimizing the P5' residue, we improve the potency or selectivity of existing inhibitors for kallikrein-related peptidase 5 and show that a variant with substitutions at 7 of the scaffold's 14 residues retains a similar structure to SFTI-1. These findings provide new insights into P5' specificity requirements for the Bowman-Birk inhibitory loop.

PubMed: 30888159
DOI: 10.1021/acs.jmedchem.9b00211

実験手法

SOLUTION NMR