The structure of T6 human insulin at 1.0 Å resolution

• Published in: Acta crystallographica. Section D, Biological crystallography. Vol. 59; no. 3; pp. 474 - 482
• Main Authors: Smith, G. David, Pangborn, Walter A., Blessing, Robert H.
• Format: Journal Article
• Language: English
• Published: 5 Abbey Square, Chester, Cheshire CH1 2HU, England Munksgaard International Publishers 01-03-2003
• Subjects: conformational displacement; Crystallization; Crystallography, X-Ray; Humans; Hydrogen Bonding; Insulin - chemistry; Models, Molecular; Phenylalanine - chemistry; Protein Conformation; T6 human insulin; Weightlessness; X-Ray Diffraction; Zinc - chemistry
• ISSN: 1399-0047; 0907-4449; 1399-0047
• DOI: 10.1107/S0907444902023685

The structure of T6 human insulin has been determined at 120 K at a resolution of 1.0 Å and refined to a residual of 0.183. As a result of cryofreezing, the first four residues of the B chain in one of the two crystallographically independent AB monomers in the hexameric [Zn1/3(AB)2Zn1/3]3 complex undergo a conformational shift that displaces the Cα atom of PheB1 by 7.86 Å relative to the room‐temperature structure. A least‐squares superposition of all backbone atoms of the room‐temperature and low‐temperature structures yielded a mean displacement of 0.422 Å. Omitting the first four residues of the B chain reduced the mean displacement to 0.272 Å. At 120 K, nine residues were found to exhibit two discrete side‐chain conformations, but only two of these residues are in common with the seven residues found to have disordered side chains in the room‐temperature structure. As a result of freezing, the disorder observed at room temperature in both ArgB22 side chains is eliminated. The close contact between pairs of Oɛ2 atoms in GluB13 observed at room temperature is maintained at cryotemperature and suggests that a carboxylate–carboxylic acid centered hydrogen bond exists [—­C(=O)—O···H···O—C(=O)—] such that the H atom is equally shared between the two partially charged O atoms.