摘要
Aggregation of the amyloid b-peptide (A b) into insoluble fibrils is a key pathologi-cal event in Alzheimers disease. Zn(II) ion induces significant Ab aggregation at nearly physio-logical concentrations in vitro. In order to explore the induce mechanism, the possible binding modes of Zn(II) in Ab peptide are studied by molecular modeling method. First, the Ab species containing 1,2,4 and 12 peptides are established respectively. And next a Zn(II) ion is manually hold the different sits of the Ab species based on the experimental data and subsequently the coordinate atom and number are assigned. Finally, the optimum binding site is found by the system energy minimization. Modeling results show that in soluble Zn(II) complex, Nt of imidazole ring of His14, O of carbonyl of main-chain, and two O of water occupy the four ligand positions of the tetrahedral complex; in the aggregation of Ab, the His13(Nt)-Zn(II)-His14(Nt) bridges are formed by Zn(II) cross-linking action. Therefore, the possible Zn(II) binding mode obtained by the studies will be helpful to reveal the form mechanism of pathogenic aggregates in brain.
Aggregation of the amyloid b-peptide (A b) into insoluble fibrils is a key pathologi-cal event in Alzheimers disease. Zn(II) ion induces significant Ab aggregation at nearly physio-logical concentrations in vitro. In order to explore the induce mechanism, the possible binding modes of Zn(II) in Ab peptide are studied by molecular modeling method. First, the Ab species containing 1,2,4 and 12 peptides are established respectively. And next a Zn(II) ion is manually hold the different sits of the Ab species based on the experimental data and subsequently the coordinate atom and number are assigned. Finally, the optimum binding site is found by the system energy minimization. Modeling results show that in soluble Zn(II) complex, Nt of imidazole ring of His14, O of carbonyl of main-chain, and two O of water occupy the four ligand positions of the tetrahedral complex; in the aggregation of Ab, the His13(Nt)-Zn(II)-His14(Nt) bridges are formed by Zn(II) cross-linking action. Therefore, the possible Zn(II) binding mode obtained by the studies will be helpful to reveal the form mechanism of pathogenic aggregates in brain.
基金
This work was supported by the National Natural Science Foundation of China (Grant No. 20171031).
