EXPLORATION OF BINDING OF HUMAN GROWTH HORMONE TO ITS RECEPTOR

人类生长激素与其受体结合的探索

• 批准号: 6456714
• 负责人: DONNA HENDRIX
• 金额: $ 27.32万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-07-01 至 2003-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6456714
• 关键词: AIDS; biological products; biomedical resource; enzymes; immunology; infection; inflammation; lymphatic system; virus

Human growth hormone (hGH) binds to its receptor (hGHr) in a three-body interaction: one molecule of the hormone and two identical monomers of the receptor form a trimer. Curiously, the hormone-receptor interactions in the trimer are not equivalent and the formation of the complex occurs in a specific kinetic order. We have modeled the recognition of hGH to the hGHr using shape complementarity of the three-dimensional structures and macromolecular docking to explore possible binding modes between the receptor and hormone. The method is based upon matching complementary-shaped strategic sites on the molecular surface. We modified the procedure to examine three-body systems. We found that the order of binding seen experimentally is also essential to our model. We explored the use of mutational data available for hGH to guide our model. In addition to docking hGH to the hGHr, we further tested our methodology by successfully reproducing sixteen macromolecular complexes from X-ray crystal structures, including enzyme-inhibitor, antibody-antigen, protein dimer and protein-DNA complexes.

人类生长激素（hGH）与受体（hGHr）结合