Crystallization and 1.6 Å resolution crystal structure of an acylated GLP-1/GIP analogue peptide
File(s)
Published version
Author(s)
Mitchell, Hamish M
Nocek, Boguslaw
Guinn, Emily J
Heng, Jerry YY
Type
Journal Article
Abstract
With the meteoric rise in interest in GLP-1 and GIP analogue peptides in recent years, there is a drive for the use of alternative purification techniques to alleviate processing bottlenecks and reduce the cost of peptide manufacturing. However, a lack of reported crystal structures for this class of peptides has hindered molecular-scale understanding of GLP-1/GIP analogue peptide crystallization, particularly related to acylated peptides. This paper therefore reports what is believed to be the first crystal structure of a GLP-1 and GIP analogue lipopeptide. Crystals obtained using a microseed matrix-screening protocol diffracted to ≤1.6 Å resolution in space group P43, with unit-cell parameters a = b = 64.66, c = 11.42 Å. Model building and the resultant structural analysis reveals that the predominantly helical peptide forms a uniquely porous spiral crystal structure composed of clockwise-ascending monomers in a square pattern, with aromatic C⋯H—π interactions around Phe22 forming the primary crystal contact between neighbouring square motifs.
Date Issued
2026-04-01
Date Acceptance
2026-02-20
Citation
Acta Crystallographica Section F:Structural Biology Communications, 2026, 82 (4), pp.114-124
ISSN
2053-230X
Publisher
International Union of Crystallography
Start Page
114
End Page
124
Journal / Book Title
Acta Crystallographica Section F:Structural Biology Communications
Volume
82
Issue
4
Copyright Statement
Published under a CC BY 4.0 licence This is an open-access article distributed under the terms of the Creative Commons Attribution (CC-BY) Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original authors and source are cited.
License URL
Identifier
https://www.ncbi.nlm.nih.gov/pubmed/41841205
PII: S2053230X26001937
Subjects
GLP-1
crystallization
diabetes
obesity
peptides
Crystallography, X-Ray
Crystallization
Glucagon-Like Peptide 1
Amino Acid Sequence
Gastric Inhibitory Polypeptide
Acylation
Models, Molecular
Publication Status
Published
Coverage Spatial
United States
Article Number
F82
Date Publish Online
2026-03-17