5UJH

ov-GRN12-34

5UJH の概要

• エントリーDOI: 10.2210/pdb5ujh/pdb
• 関連するPDBエントリー: 5UJG
• NMR情報: BMRB: 30233
• 分子名称: Granulin (1 entity in total)
• 機能のキーワード: wound healing agent, structure calculation, structure from cyana 3.97, cytokine
• 由来する生物種: Opisthorchis viverrini
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 2457.81

構造登録者

Bansal, P.,Smout, M.,Wilson, D.,Caceres, C.C.,Dastpeyman, M.,Sotillo, J.,Seifert, J.,Brindley, P.,Loukas, A.,Daly, N. (登録日: 2017-01-18, 公開日: 2018-01-24, 最終更新日: 2024-10-23)

主引用文献

Bansal, P.S.,Smout, M.J.,Wilson, D.,Cobos Caceres, C.,Dastpeyman, M.,Sotillo, J.,Seifert, J.,Brindley, P.J.,Loukas, A.,Daly, N.L.
Development of a Potent Wound Healing Agent Based on the Liver Fluke Granulin Structural Fold.
J. Med. Chem., 60:4258-4266, 2017

PubMed Abstract: Granulins are a family of protein growth factors that are involved in cell proliferation. An orthologue of granulin from the human parasitic liver fluke Opisthorchis viverrini, known as Ov-GRN-1, induces angiogenesis and accelerates wound repair. Recombinant Ov-GRN-1 production is complex and poses an obstacle for clinical development. To identify the bioactive region(s) of Ov-GRN-1, four truncated N-terminal analogues were synthesized and characterized structurally using NMR spectroscopy. Peptides that contained only two native disulfide bonds lack the characteristic granulin β-hairpin structure. Remarkably, the introduction of a non-native disulfide bond was critical for formation of β-hairpin structure. Despite this structural difference, both two and three disulfide-bonded peptides drove proliferation of a human cholangiocyte cell line and demonstrated potent wound healing in mice. Peptides derived from Ov-GRN-1 are leads for novel wound healing therapeutics, as they are likely less immunogenic than the full-length protein and more convenient to produce.

PubMed: 28425707
DOI: 10.1021/acs.jmedchem.7b00047

実験手法

SOLUTION NMR