7OCM

K1K1H6, a potent recombinant minimal hepatocyte growth factor/scatter factor mimic

7OCM の概要

• エントリーDOI: 10.2210/pdb7ocm/pdb
• 分子名称: Hepatocyte growth factor alpha chain,Hepatocyte growth factor alpha chain, 4-(2-HYDROXYETHYL)-1-PIPERAZINE ETHANESULFONIC ACID (3 entities in total)
• 機能のキーワード: met receptor agonist, hgf/sf kringle 1 dimer, hgf/sf-derived recombinant protein, met-activator, regeneration of epithelial tissue and organs, engineered growth factor, de novo protein
• 由来する生物種: Homo sapiens (Human); 詳細
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 20538.15

構造登録者

de Jonge, H.,de Nola, G.,Gherardi, E. (登録日: 2021-04-27, 公開日: 2021-07-07, 最終更新日: 2024-10-16)

主引用文献

de Nola, G.,Leclercq, B.,Mougel, A.,Taront, S.,Simonneau, C.,Forneris, F.,Adriaenssens, E.,Drobecq, H.,Iamele, L.,Dubuquoy, L.,Melnyk, O.,Gherardi, E.,de Jonge, H.,Vicogne, J.
Dimerization of kringle 1 domain from hepatocyte growth factor/scatter factor provides a potent MET receptor agonist.
Life Sci Alliance, 5:-, 2022

PubMed Abstract: Hepatocyte growth factor/scatter factor (HGF/SF) and its cognate receptor MET play several essential roles in embryogenesis and regeneration in postnatal life of epithelial organs such as the liver, kidney, lung, and pancreas, prompting a strong interest in harnessing HGF/SF-MET signalling for regeneration of epithelial organs after acute or chronic damage. The limited stability and tissue diffusion of native HGF/SF, however, which reflect the tightly controlled, local mechanism of action of the morphogen, have led to a major search of HGF/SF mimics for therapy. In this work, we describe the rational design, production, and characterization of K1K1, a novel minimal MET agonist consisting of two copies of the kringle 1 domain of HGF/SF in tandem orientation. K1K1 is highly stable and displays biological activities equivalent or superior to native HGF/SF in a variety of in vitro assay systems and in a mouse model of liver disease. These data suggest that this engineered ligand may find wide applications in acute and chronic diseases of the liver and other epithelial organs dependent of MET activation.

PubMed: 35905995
DOI: 10.26508/lsa.202201424

実験手法

X-RAY DIFFRACTION (1.7 Å)