Acta Chimica Sinica ›› 2011, Vol. 69 ›› Issue (03): 253-261.     Next Articles

Full Papers

桑色素与基质金属蛋白酶中催化锌离子相互作用机理的理论研究

张骥*,1,李婷2,陆涛3,孟卫1,余丹妮1,陈亚东1   

  1. (1中国药科大学物理化学教研室 南京 210009)
    (2中国药科大学药学院 南京 210009)
    (3中国药科大学有机化学教研室 南京 210009)
  • 收稿日期:2010-07-29 修回日期:2010-10-06 出版日期:2011-02-14 发布日期:2010-10-26
  • 通讯作者: 张骥 E-mail:jzhang@cpu.edu.cn
  • 基金资助:

    中国药科大学人才引进基金资助项目

Theoretical Studies on the Mechanisms of Interaction between Morin and the Catalytic Zinc Ion in Matrix Metalloproteinases

Zhang Ji*,1 Li Ting2 Lu Tao3 Meng Wei1 Yu Danni1 Chen Yadong1   

  1. (1 Department of Physical Chemistry, China Pharmaceutical University, Nanjing 210009)
    (2 School of Pharmacy, China Pharmaceutical University, Nanjing 210009)
    (3 Department of Organic Chemistry, China Pharmaceutical University, Nanjing 210009)
  • Received:2010-07-29 Revised:2010-10-06 Online:2011-02-14 Published:2010-10-26
  • Contact: Ji ZHANG E-mail:jzhang@cpu.edu.cn

The mechanisms of interaction between morin and the catalytic zinc ion (Zn2+) in matrix metalloproteinases (MMPs) are investigated by using PM6 quantum chemistry method and designing ligand-exchange reactions. It is found that the electron transfer from morin molecule to catalytic zinc ion occurs when the groups at the various positions of A, B and C rings of morin molecule coordinate with catalytic zinc ion in MMPs, and the more the electron transfer, the stronger coordinating ability between them. We further find that among the groups at the various positions of morin molecule, the coordinating ability between the oxygen atom of the carbonyl group at the 4-position and catalytic zinc ion is the strongest, which indicates that the inhibition of MMPs activities is produced mainly by the carbonyl group at the 4-position of morin, rather than the hydroxy groups at the other positions. Regression analysis show that there are better linear relationships between the calculated free energy changes (DG298) for the 6 ligand-exchange reactions and the Zn—O bond length, total atomic charges in the morin molecule, and the charges of coordinating O atoms in the produced coordinating ions. Our calculated results are in agreement with available experimental and theoretical results. These results of the interaction mechanisms may provide important reference data for the structural modifications of the morin molecule to design the MMPs inhibitors whose biological activities can obviously be improved.

Key words: morin, matrix metalloproteinases (MMPs), mechanism, PM6, free energy