1uz9: Difference between revisions
No edit summary |
No edit summary |
||
| Line 1: | Line 1: | ||
[[Image:1uz9.gif|left|200px]] | [[Image:1uz9.gif|left|200px]] | ||
<!-- | |||
The line below this paragraph, containing "STRUCTURE_1uz9", creates the "Structure Box" on the page. | |||
You may change the PDB parameter (which sets the PDB file loaded into the applet) | |||
or the SCENE parameter (which sets the initial scene displayed when the page is loaded), | |||
| | or leave the SCENE parameter empty for the default display. | ||
| | --> | ||
{{STRUCTURE_1uz9| PDB=1uz9 | SCENE= }} | |||
}} | |||
'''CRYSTALLOGRAPHIC AND SOLUTION STUDIES OF N-LITHOCHOLYL INSULIN: A NEW GENERATION OF PROLONGED-ACTING INSULINS.''' | '''CRYSTALLOGRAPHIC AND SOLUTION STUDIES OF N-LITHOCHOLYL INSULIN: A NEW GENERATION OF PROLONGED-ACTING INSULINS.''' | ||
| Line 19: | Line 16: | ||
==About this Structure== | ==About this Structure== | ||
1UZ9 is a [[Protein complex]] structure | 1UZ9 is a [[Protein complex]] structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1UZ9 OCA]. | ||
==Reference== | ==Reference== | ||
| Line 32: | Line 29: | ||
[[Category: Whittingham, J L.]] | [[Category: Whittingham, J L.]] | ||
[[Category: Wilkinson, A J.]] | [[Category: Wilkinson, A J.]] | ||
[[Category: | [[Category: Diabetes mellitus]] | ||
[[Category: | [[Category: Hormone disease mutation]] | ||
[[Category: | [[Category: Insulin]] | ||
[[Category: | [[Category: Insulin family]] | ||
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 11:53:35 2008'' | |||
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | |||
Revision as of 11:53, 3 May 2008
CRYSTALLOGRAPHIC AND SOLUTION STUDIES OF N-LITHOCHOLYL INSULIN: A NEW GENERATION OF PROLONGED-ACTING INSULINS.
OverviewOverview
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.
About this StructureAbout this Structure
1UZ9 is a Protein complex structure. Full crystallographic information is available from OCA.
ReferenceReference
Crystallographic and solution studies of N-lithocholyl insulin: a new generation of prolonged-acting human insulins., Whittingham JL, Jonassen I, Havelund S, Roberts SM, Dodson EJ, Verma CS, Wilkinson AJ, Dodson GG, Biochemistry. 2004 May 25;43(20):5987-95. PMID:15147182 Page seeded by OCA on Sat May 3 11:53:35 2008