1XDA

STRUCTURE OF INSULIN

Summary for 1XDA

• Entry DOI: 10.2210/pdb1xda/pdb
• Descriptor: FATTY ACID ACYLATED INSULIN, PHENOL, ZINC ION, ... (7 entities in total)
• Functional Keywords: hormone, metabolic role, chemical activity, insulin albumin, fatty acid, glucose metabolism, diabetes
• Biological source: Homo sapiens (human); More
• Cellular location: Secreted: P01308 P01308
• Total number of polymer chains: 8
• Total formula weight: 24559.56

Authors

Whittingham, J.L.,Havelund, S.,Jonassen, I. (deposition date: 1996-12-18, release date: 1997-07-07, Last modification date: 2024-10-09)

Primary citation

Whittingham, J.L.,Havelund, S.,Jonassen, I.
Crystal structure of a prolonged-acting insulin with albumin-binding properties.
Biochemistry, 36:2826-2831, 1997

PubMed Abstract: The fatty acid acylated insulin, Lys(B29)-tetradecanoyl, des-(B30) human insulin, has been crystallized and the structure determined by X-ray crystallography. The fatty acid substituent on residue B29 Lys binds reversibly to circulating albumin protein in vivo, and by this mechanism the hormone's action is prolonged. Crystals of the fatty acid insulin grow in space group R3, with two dimers in the asymmetric unit, and diffract to 1.8 A spacing. The structure has been solved by molecular replacement and refined using a maximum likelihood method. The crystal structure consists of R6 zinc insulin hexamers which contain phenol. The fatty acids can be seen bound between the hexamers, making specific interactions with the side chains of residue B1 Phe; however, the lysine side chains to which the fatty acids are covalently attached are mostly disordered. The mode of binding of the fatty acids appears to be determined by crystal packing, and whether or not they interact with the protein in this way in solution remains uncertain.

PubMed: 9062110
DOI: 10.1021/bi9625105

Experimental method

X-RAY DIFFRACTION (1.8 Å)