6E1L

GRN3Ala

Summary for 6E1L

• Entry DOI: 10.2210/pdb6e1l/pdb
• NMR Information: BMRB: 30232
• Descriptor: Granulin (1 entity in total)
• Functional Keywords: wound healing agent, granulin, structure from cyana 3.97, cytokine
• Biological source: Opisthorchis viverrini
• Total number of polymer chains: 1
• Total formula weight: 2514.91

Authors

Dastpeyman, M.,Bansal, P.,Wilson, D.,Sotillo, J.,Brindley, P.,Loukas, A.,Smout, M.,Daly, N. (deposition date: 2018-07-10, release date: 2019-02-06, Last modification date: 2024-10-23)

Primary citation

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

Experimental method

SOLUTION NMR