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1.2 A structure of T3R3 human insulin at 100 K

Contents 1 Overview 2 Disease 3 About this Structure 4 Reference

Overview

The structure of T(3)R(3) hexameric human insulin has been determined at, 100 K from two different crystals at 1.2 and 1.3 A resolution and refined, to residuals of 0.169 and 0.176, respectively. Owing to a phase change, the c axis is double its room-temperature value and the asymmetric unit, contains two independent TR(f) insulin dimers. Compared with the, orientation in the room-temperature structure, one dimer undergoes a, rotation about the c axis of -5 degrees, while the second is rotated +4, degrees. A superposition of the backbone atoms of the two independent, dimers shows that the C(alpha) atoms of five residues within the, R(f)-state monomers are displaced by more than 1.0 A; smaller, displacements are observed for the T-state monomers. Four zinc ions lie on, the crystallographic threefold axis and each forms bonds to three, symmetry-related HisB10 N(varepsilon2) atoms from the T- and R(f)-state, trimers. While three of the zinc ions are tetrahedrally coordinated with a, chloride ion completing the coordination sphere, mixed, tetrahedral/octahedral coordination is observed for one of the T-state, zinc ions. The three symmetry-related "phenolic binding sites" in one, hexamer contain water molecules and a glycerol molecule, but the same, sites in the second hexamer are occupied by a zinc ion coordinated to an, alternate conformation of HisB10, a symmetry-related HisB5 and two, chloride ions. Two additional and partially occupied zinc ion sites are, observed at the interface between the two independent dimers. One zinc ion, is coordinated by a T-state HisB5 of one dimer, an R-state HisB5 of the, second dimer and two water molecules; the second zinc ion is coordinated, by an alternate side-chain conformation of the T-state HisB5 and three, water molecules. The carboxyl group of one GluB13 side chain, which exists, in two discrete conformations, appears to be protonated, because short, contacts exist to a second carboxyl group or to a carbonyl O atom.

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

1G7A is a Protein complex structure of sequences from [1] with ZN, CL, GOL and ACN as ligands. Full crystallographic information is available from OCA.

Reference

Phase changes in T(3)R(3)(f) human insulin: temperature or pressure induced?, Smith GD, Pangborn WA, Blessing RH, Acta Crystallogr D Biol Crystallogr. 2001 Aug;57(Pt 8):1091-100. Epub 2001, Jul 23. PMID:11468392

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