2MMT

Lasso peptide-based integrin inhibitor: Microcin J25 variant with RGDF substitution of Gly12-Ile13-Gly14-Thr15

2MMT の概要

• エントリーDOI: 10.2210/pdb2mmt/pdb
• NMR情報: BMRB: 19865
• 分子名称: Microcin J25 RGDF mutant (1 entity in total)
• 機能のキーワード: lasso peptide, epitope grafting, integrin inhibitor, drug design, molecular scaffolds, molecular dynamics, antibiotic
• 由来する生物種: Escherichia coli
• 細胞内の位置: Secreted: Q9X2V7
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 2274.49

構造登録者

Hegemann, J.D.,Zimmermann, M.,Knappe, T.A.,Xie, X.,Marahiel, M.A. (登録日: 2014-03-18, 公開日: 2014-07-02, 最終更新日: 2024-11-06)

主引用文献

Hegemann, J.D.,De Simone, M.,Zimmermann, M.,Knappe, T.A.,Xie, X.,Di Leva, F.S.,Marinelli, L.,Novellino, E.,Zahler, S.,Kessler, H.,Marahiel, M.A.
Rational improvement of the affinity and selectivity of integrin binding of grafted lasso peptides.
J.Med.Chem., 57:5829-5834, 2014

PubMed Abstract: Integrins moderate diverse important functions in the human body and are promising targets in cancer therapy. Hence, the selective inhibition of specific integrins is of great medicinal interest. Here, we report the optimization of a grafted lasso peptide, yielding MccJ25(RGDF), which is a highly potent and selective αvβ3 integrin inhibitor. Furthermore, its NMR structure was elucidated and employed in a molecular dynamics approach, revealing information about the integrin binding mode and selectivity profile of MccJ25(RGDF).

PubMed: 24949551
DOI: 10.1021/jm5004478

実験手法

SOLUTION NMR