2omg: Difference between revisions
New page: left|200px<br /> <applet load="2omg" size="450" color="white" frame="true" align="right" spinBox="true" caption="2omg, resolution 1.52Å" /> '''Structure of human ... |
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[[Image:2omg.gif|left|200px]]<br /> | [[Image:2omg.gif|left|200px]]<br /><applet load="2omg" size="350" color="white" frame="true" align="right" spinBox="true" | ||
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caption="2omg, resolution 1.52Å" /> | caption="2omg, resolution 1.52Å" /> | ||
'''Structure of human insulin cocrystallized with protamine and urea'''<br /> | '''Structure of human insulin cocrystallized with protamine and urea'''<br /> | ||
==Overview== | ==Overview== | ||
Insulin NPH (neutral protamine hagedorn) has for long been one of the most | 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. | ||
==Disease== | ==Disease== | ||
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==About this Structure== | ==About this Structure== | ||
2OMG is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with ZN, CL, NA, CRS, URE and ARF as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http:// | 2OMG is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=ZN:'>ZN</scene>, <scene name='pdbligand=CL:'>CL</scene>, <scene name='pdbligand=NA:'>NA</scene>, <scene name='pdbligand=CRS:'>CRS</scene>, <scene name='pdbligand=URE:'>URE</scene> and <scene name='pdbligand=ARF:'>ARF</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2OMG OCA]. | ||
==Reference== | ==Reference== | ||
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[[Category: insulin nph like crystal]] | [[Category: insulin nph like crystal]] | ||
''Page seeded by [http:// | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 18:20:07 2008'' | ||
Revision as of 19:20, 21 February 2008
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Structure of human insulin cocrystallized with protamine and 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.
DiseaseDisease
Known diseases associated with this structure: Diabetes mellitus, rare form OMIM:[176730], Hyperproinsulinemia, familial OMIM:[176730], MODY, one form OMIM:[176730]
About this StructureAbout this Structure
2OMG is a Protein complex structure of sequences from Homo sapiens with , , , , and as ligands. 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
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