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  • 标题:Multifunctional receptor model for dioxin and related compound toxic action: possible thyroid hormone-responsive effector-linked site.
  • 作者:J D McKinney
  • 期刊名称:Environmental Health Perspectives
  • 印刷版ISSN:0091-6765
  • 电子版ISSN:1552-9924
  • 出版年度:1989
  • 卷号:82
  • 页码:323
  • 语种:English
  • 出版社:OCR Subscription Services Inc
  • 摘要:Molecular/theoretical modeling studies have revealed that thyroid hormones and toxic chlorinated aromatic hydrocarbons of environmental significance (for which dioxin or TCDD is the prototype) have similar structural properties that could be important in molecular recognition in biochemical systems. These molecular properties include a somewhat rigid, sterically accessible and polarizable aromatic ring and size-limited, hydrophobic lateral substituents, usually contained in opposite adjoining rings of a diphenyl compound. These molecular properties define the primary binding groups thought to be important in molecular recognition of both types of structures in biochemical systems. Similar molecular reactivities are supported by the demonstration of effective specific binding of thyroid hormones and chlorinated aromatic hydrocarbons with four different proteins, enzymes, or receptor preparations that are known or suspected to be involved in the expression of thyroid hormone activity. These binding interactions represent both aromatic-aromatic (stacking) and molecular cleft-type recognition processes. A multiple protein or multifunctional receptor-ligand binding mechanism model is proposed as a way of visualizing the details and possible role of both the stacking and cleft type molecular recognition factors in the expression of biological activity. The model suggests a means by which hormone-responsive effector-linked sites (possible protein-protein-DNA complexes) can maintain highly structurally specific control of hormone action. Finally, the model also provides a theoretical basis for the design and conduct of further biological experimentation on the molecular mechanism(s) of action of toxic chlorinated aromatic hydrocarbons and thyroid hormones. Full text Full text is available as a scanned copy of the original print version. Get a printable copy (PDF file) of the complete article (3.2M), or click on a page image below to browse page by page. Links to PubMed are also available for Selected References . 323 324 325 326 327 328 329 330 331 332 333 334 335 336
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