Peptidyl-Prolyl cis/trans Isomerases and Their Effectors

Changes in the conformation of the units within the peptide chain are the elementary processes in the folding of a protein into its native three-dimensional structure. Even a few years ago protein folding in vivo was considered to be an autonomous process not requiring the help of enzymes or auxiliary substances. Recently an increasing number of proteins that assist in the folding process have been found; these include enzymes that catalyze conformational interconversions. The cis/trans isomerization of the petptide bond N-terminal to a praline residue is catalyzed by peptidyl-prolyl cis/trans isomerases (PPIases). Two families of these ubiquitous and phylogenetically highly conserved enzymes are known, the cyclophilins and FK506-binding proteins. Their catalytic activity is extremely highmdash;the rate constants for the bimolecular reactions they catalyze approach the diffusion-controlled limit for enzyme-substrate reactions. These enzymes increase the rate of isomerization in oligopeptides as well as in intermediate in protein folding. It is not yet known which structural units in the cell serve as substrates and exactly which reactions are catalyzed. However, these isomerases have been shown to interact with the heat shock proteins of the nonactivated steroid receptors and with the gag polyprotein of the AIDS HIV-1 virus. The immunosuppressive agents cyclosporine A and FK506 are highly effective inhibitors for PPIases. Surprisingly these compounds affect the signal cascade of T cells but not through enzyme inhibition; the inhibitor-enzyme complexes themselves are the active agents. These complexes exhibit properties not displayed by the individual components and thus are able to affect other cellular components. The current model of the suppression of the antigen- and mitogen-stimulated clonal expansion of T cells is presented here.     

碳-13核磁共振定量测定萄葡糖及果糖的含量

本文利用~(13)C-NMR方法测量由葡萄糖通过葡萄糖异构酶的作用,在不同的条件下,在转化为果糖的过程中葡萄糖和果糖的相对含量。同时~(13)C-NMR技术也是直接测定各种构型糖含量的有效方法。实验结果表明,Gd-DPTA弛予试剂能够使自旋-晶格弛豫时间(T1)缩短。同时对NOE效应的消除也作了描述。本法测定的相对误差低于±0.5％。