2omh: Difference between revisions

Revision as of 11:12, 4 May 2008

Structure of human insulin cocrystallized with ARG-12 peptide in presence of urea

OverviewOverview

Insulin NPH (neutral protamine hagedorn) has for long been one of the most important therapeutic formulations for the treatment of diabetes. The protracted action profile of NPH formulations is gained from crystallizing insulin with zinc in the presence of the basic poly-arginine peptide protamine. In spite of its long history and successful use, the binding mode of the insulin-protamine complex is not known. In this study, three different systems were used to study protamine binding to insulin. In the first system, crystals of an insulin-protamine complex grown in the presence of urea and diffracting to 1.5A resolution were analyzed. In the second system, a shorter peptide consisting of 12 arginine residues was co-crystallized with insulin in order to reduce the flexibility and thereby improve the electron density of the peptide. Both systems yielded data to a significantly higher resolution than obtained previously. In addition, a third system was analyzed where crystals of insulin and protamine were grown in the absence of urea, with conditions closely resembling the pharmaceutical formulation. Data from these NPH microcrystals could for the first time be collected to 2.2A resolution at a micro focused X-ray beamline. Analysis of all three crystal forms reveal potential protamine density located close to the solvent channel leading to the centrally located zinc atoms in the insulin hexamer and support that protamine binds to insulin in a not well defined conformation.

About this StructureAbout this Structure

2OMH is a Protein complex structure of sequences from Homo sapiens. Full crystallographic information is available from OCA.

ReferenceReference

Structural characterization of insulin NPH formulations., Norrman M, Hubalek F, Schluckebier G, Eur J Pharm Sci. 2007 Apr;30(5):414-23. Epub 2007 Jan 20. PMID:17339105 Page seeded by OCA on Sun May 4 11:12:51 2008

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OCA

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 [[Image:2omh.gif|left|200px]]
- {{Structure
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-|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2omh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2omh OCA], [http://www.ebi.ac.uk/pdbsum/2omh PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=2omh RCSB]</span>
-}}
 '''Structure of human insulin cocrystallized with ARG-12 peptide in presence of urea'''
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 [[Category: Norrman, M.]]
 [[Category: Schluckebier, G.]]
-[[Category: insulin nph-like crystal]]
+[[Category: Insulin nph-like crystal]]
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun May  4 11:12:51 2008''
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 04:19:59 2008''