2omi

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spinqualitylabelsall models 2omi, resolution 2.24Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image

Structure of human insulin cocrystallized with protamine

Contents 1 Overview 2 Disease 3 About this Structure 4 Reference

Overview

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

Known diseases associated with this structure: Diabetes mellitus, rare form OMIM:[176730], Hyperproinsulinemia, familial OMIM:[176730], MODY, one form OMIM:[176730]

About this Structure

2OMI is a Protein complex structure of sequences from Homo sapiens with ZN, CL and RCO as ligands. Full crystallographic information is available from OCA.

Reference

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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