Open AccessI 222 crystal form of despentapeptide (B26–B30) insulin provides new insights into the properties of monomeric insulin
Author(s) -
Whittingham Jean L.,
Youshang Zhang,
Žáková Lenka,
Dodson Eleanor J.,
Turkenburg Johan P.,
Brange Jens,
Dodson G. Guy
Publication year - 2006
Publication title -
acta crystallographica section d
Language(s) - English
Resource type - Journals
ISSN - 1399-0047
DOI - 10.1107/s0907444906006871
Subject(s) - random hexamer , dimer , crystallography , chemistry , molecule , monomer , crystal structure , van der waals force , stereochemistry , polymer , organic chemistry
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 Å spacing (space group I 222) revealed that the DPI molecule, which is unable to make β‐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 α‐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 Å displacement of the B20–B23 β‐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.