Whittingham Jean L, Youshang Zhang, Záková Lenka, Dodson Eleanor J, Turkenburg Johan P, Brange Jens, Dodson G Guy
York Structural Biology Laboratory, Department of Chemistry, University of York, Heslington, York YO10 5YW, England.
Acta Crystallogr D Biol Crystallogr. 2006 May;62(Pt 5):505-11. doi: 10.1107/S0907444906006871. Epub 2006 Apr 19.
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.
去五肽（去B26 - B30）胰岛素（DPI）是一种活性修饰胰岛素，已在pH 2的20%乙酸存在下结晶。对间距为1.8 Å（空间群I222）的晶体结构分析表明，DPI分子无法形成用于生理二聚体形成的β链相互作用，且在溶液中显然为单体形式，但却形成了一种由晶格产生的替代二聚体。这种二聚体的形成涉及包括B9 - B19α螺旋（通常被天然六聚体内的二聚体 - 二聚体接触所掩埋）在内的表面之间的相互作用。二聚体内两个晶体学独立的分子基本相同，其构象与T(6)胰岛素六聚体中所见的T态胰岛素相似。二聚体中每个分子的一个不寻常特征是在B链C末端（残基B20 - B25）存在两种独立的构象。这两种构象均与天然胰岛素不同，涉及B20 - B23β转角有3.5 Å的位移以及PheB25残基的重新定位，使得它与分子主体形成紧密的范德华接触，似乎稳定了B链C末端。
