1UZ9

Crystallographic and solution studies of N-lithocholyl insulin: a new generation of prolonged-acting insulins.

1UZ9 の概要

• エントリーDOI: 10.2210/pdb1uz9/pdb
• 関連するPDBエントリー: 1A7F 1AI0 1AIY 1B9E 1BEN 1EFE 1EV3 1EV6 1EVR 1FU2 1FUB 1G7A 1G7B 1GUJ 1HIQ 1HIS 1HIT 1HLS 1HTV 1HUI 1IOG 1IOH 1J73 1JCA 1JCO 1K3M 1KMF 1LKQ 1LNP 1LPH 1MHI 1MHJ 1MSO 1OS3 1OS4 1Q4V 1QIY 1QIZ 1QJ0 1SJT 1SJU 1TRZ 1TYL 1TYM 1VKT 1XDA 1XGL 1ZEG 1ZEH 1ZNJ 2AIY 2HIU 3AIY 4AIY 5AIY
• 分子名称: INSULIN, M-CRESOL, (2S)-2-AMINO-6-({(4R)-4-[(10R,13S)-10,13-DIMETHYL-3-OXOHEXADECAHYDRO-1H-CYCLOPENTA[A]PHENANTHREN-17-YL]PENTANOYL}AMINO)HEXANOIC ACID, ... (7 entities in total)
• 機能のキーワード: insulin, diabetes mellitus, insulin family, hormone disease mutation
• 由来する生物種: HOMO SAPIENS (HUMAN); 詳細
• 細胞内の位置: Secreted: P01308 P01308
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 6428.28

構造登録者

Whittingham, J.L.,Jonassen, I.,Havelund, S.,Roberts, S.M.,Dodson, E.J.,Verma, C.S.,Wilkinson, A.J.,Dodson, G.G. (登録日: 2004-03-08, 公開日: 2005-03-03, 最終更新日: 2023-12-13)

主引用文献

Whittingham, J.L.,Jonassen, I.,Havelund, S.,Roberts, S.M.,Dodson, E.J.,Verma, C.S.,Wilkinson, A.J.,Dodson, G.G.
Crystallographic and Solution Studies of N-Lithocholyl Insulin: A New Generation of Prolonged-Acting Human Insulins
Biochemistry, 43:5987-, 2004

PubMed Abstract: The addition of specific bulky hydrophobic groups to the insulin molecule provides it with affinity for circulating serum albumin and enables it to form soluble macromolecular complexes at the site of subcutaneous injection, thereby securing slow absorption of the insulin analogue into the blood stream and prolonging its half-life once there. N-Lithocholic acid acylated insulin [Lys(B29)-lithocholyl des-(B30) human insulin] has been crystallized and the structure determined by X-ray crystallography at 1.6 A resolution to explore the molecular basis of its assembly. The unit cell in the crystal consists of an insulin hexamer containing two zinc ions, with two m-cresol molecules bound at each dimer-dimer interface stabilizing an R(6) conformation. Six covalently bound lithocholyl groups are arranged symmetrically around the outside of the hexamer. These form specific van der Waals and hydrogen-bonding interactions at the interfaces between neighboring hexamers, possibly representing the kinds of interactions which occur in the soluble aggregates at the site of injection. Comparison with an equivalent nonderivatized native insulin hexamer shows that the addition of the lithocholyl group disrupts neither the important conformational features of the insulin molecule nor its hexamer-forming ability. Indeed, binding studies show that the affinity of N-lithocholyl insulin for the human insulin receptor is not significantly diminished.

PubMed: 15147182
DOI: 10.1021/BI036163S

実験手法

X-RAY DIFFRACTION (1.6 Å)