6E1L

GRN3Ala

6E1L の概要

• エントリーDOI: 10.2210/pdb6e1l/pdb
• NMR情報: BMRB: 30232
• 分子名称: Granulin (1 entity in total)
• 機能のキーワード: wound healing agent, granulin, 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: 2514.91

構造登録者

Dastpeyman, M.,Bansal, P.,Wilson, D.,Sotillo, J.,Brindley, P.,Loukas, A.,Smout, M.,Daly, N. (登録日: 2018-07-10, 公開日: 2019-02-06, 最終更新日: 2024-10-23)

主引用文献

Dastpeyman, M.,Bansal, P.S.,Wilson, D.,Sotillo, J.,Brindley, P.J.,Loukas, A.,Smout, M.J.,Daly, N.L.
Structural Variants of a Liver Fluke Derived Granulin Peptide Potently Stimulate Wound Healing.
J. Med. Chem., 61:8746-8753, 2018

PubMed Abstract: Granulins are a family of growth factors involved in cell proliferation. The liver-fluke granulin, Ov-GRN-1, isolated from a carcinogenic liver fluke Opisthorchis viverrini, can significantly accelerate wound repair in vivo and in vitro. However, it is difficult to express Ov-GRN-1 in recombinant form at high yield, impeding its utility as a drug lead. Previously we reported that a truncated analogue ( Ov-GRN) promotes healing of cutaneous wounds in mice. NMR analysis of this analogue indicates the presence of multiple conformations, most likely as a result of proline cis/ trans isomerization. To further investigate whether the proline residues are involved in adopting the multiple confirmations, we have synthesized analogues involving mutation of the proline residues. We have shown that the proline residues have a significant influence on the structure, activity, and folding of Ov-GRN. These results provide insight into improving the oxidative folding yield and bioactivity of Ov-GRN and might facilitate the development of a novel wound healing agent.

PubMed: 30183294
DOI: 10.1021/acs.jmedchem.8b00898

実験手法

SOLUTION NMR