I222 crystal form of despentapeptide (B26-B30) insulin provides new insights into the properties of monomeric insulin

Acta Crystallographica. Section D, Biological Crystallography
Jean L WhittinghamG Dodson

Abstract

Despentapeptide (des-B26-B30) insulin (DPI), an active modified insulin, has been crystallized in the presence of 20% acetic acid pH 2. A crystal structure analysis to 1.8 A spacing (space group I222) revealed that the DPI molecule, which is unable to make beta-strand interactions for physiological dimer formation and is apparently monomeric in solution, formed an alternative lattice-generated dimer. The formation of this dimer involved interactions between surfaces which included the B9-B19 alpha-helices (usually buried by the dimer-dimer contacts within the native hexamer). The two crystallographically independent molecules within the dimer were essentially identical and were similar in conformation to T-state insulin as seen in the T(6) insulin hexamer. An unusual feature of each molecule in the dimer was the presence of two independent conformations at the B-chain C-terminus (residues B20-B25). Both conformations were different from that of native insulin, involving a 3.5 A displacement of the B20-B23 beta-turn and a repositioning of residue PheB25 such that it made close van der Waals contact with the main body of the molecule, appearing to stabilize the B-chain C-terminus.

Citations

Sep 23, 2011·Biochemical Society Transactions·Guy G Dodson
Jun 24, 2011·Acta Crystallographica. Section D, Biological Crystallography·Karthik S PaithankarElspeth F Garman

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