Ⅰ. INTRODUCTIONInsulin is a hormone protein which has been investigated in a very broad and deep scope. On the basis of the abundant knowledge on its structure-function relationship, it has been an important subject ...Ⅰ. INTRODUCTIONInsulin is a hormone protein which has been investigated in a very broad and deep scope. On the basis of the abundant knowledge on its structure-function relationship, it has been an important subject for insulin studies trying to reconstitute novel insulin derivatives with some special biological activities, such as prolonged action, higher potence and lower-antigenicity, by protein engineering so as to be advantageous to the therapeutics of diabetes.展开更多
The crystal structure of 2 Zn porcine insulin has been refined at 1.2 resolution. The reciprocal space refinement was restrained by the incorporation of extensive chemical observations into the least squares equations...The crystal structure of 2 Zn porcine insulin has been refined at 1.2 resolution. The reciprocal space refinement was restrained by the incorporation of extensive chemical observations into the least squares equations. In addition to the non-hydrogen atoms, hydrogen atoms of protein, water molecules and the bulk solvent have been determined and refined. After two cycles of anisotropic refinement of non-hydrogen atoms of insulin, the final agreement factor was 0.128 for 20,005 reflexions (F_o>1σ(F_o)) in a spacing 1.2 and the root mean squares deviation from ideal covalent bond lengths was 0.021. On the electron density maps, the appearances of weight and shape of non-hydrogen atoms were very clear and reasonable. The anisotropic appearances of sulphur atoms could be seen clearly. After anisotropic refinement, the situation fit to the electron density was improved distinctly.展开更多
Ⅰ. INTRODUCTIONImmune reaction remains a challenging problem in the clinical application of various insulin preparations. It is known that about 70％ of patients will produce anti-insulin antibodies after some time e...Ⅰ. INTRODUCTIONImmune reaction remains a challenging problem in the clinical application of various insulin preparations. It is known that about 70％ of patients will produce anti-insulin antibodies after some time even if highly pure insulin is used to treat diabetes. Therefore,it is both theoretically and practically significant to understand the molecular basis of insulin immune reaction and to find new insulin preparations with low antigenicity and full bioactivity.展开更多
基金Project supported by a grant of "863" high technology.
文摘Ⅰ. INTRODUCTIONInsulin is a hormone protein which has been investigated in a very broad and deep scope. On the basis of the abundant knowledge on its structure-function relationship, it has been an important subject for insulin studies trying to reconstitute novel insulin derivatives with some special biological activities, such as prolonged action, higher potence and lower-antigenicity, by protein engineering so as to be advantageous to the therapeutics of diabetes.
基金Project supported by UNIDO Grant (91/048) and the High-Technology Program of China.
文摘The crystal structure of 2 Zn porcine insulin has been refined at 1.2 resolution. The reciprocal space refinement was restrained by the incorporation of extensive chemical observations into the least squares equations. In addition to the non-hydrogen atoms, hydrogen atoms of protein, water molecules and the bulk solvent have been determined and refined. After two cycles of anisotropic refinement of non-hydrogen atoms of insulin, the final agreement factor was 0.128 for 20,005 reflexions (F_o>1σ(F_o)) in a spacing 1.2 and the root mean squares deviation from ideal covalent bond lengths was 0.021. On the electron density maps, the appearances of weight and shape of non-hydrogen atoms were very clear and reasonable. The anisotropic appearances of sulphur atoms could be seen clearly. After anisotropic refinement, the situation fit to the electron density was improved distinctly.
基金Supported by a grant of UNIDO (91/048/CW)and "863" high technology program
文摘Ⅰ. INTRODUCTIONImmune reaction remains a challenging problem in the clinical application of various insulin preparations. It is known that about 70％ of patients will produce anti-insulin antibodies after some time even if highly pure insulin is used to treat diabetes. Therefore,it is both theoretically and practically significant to understand the molecular basis of insulin immune reaction and to find new insulin preparations with low antigenicity and full bioactivity.
