CAUSE & EFFECT OF DIMER ASYMMETRY IN MERCURIC REDUCTASE

原因

• 批准号: 6347957
• 负责人: SUSAN M MILLER
• 金额: $ 0.04万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-07-01 至 2001-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6347957
• 关键词: biomedical resource; computers; informatics; technology /technique

Mercuric ion reductase catalyzes the two-electron reduction of Hg(II) to elemental mercury as the key step in bacterial detoxification of Hg(II) and organomercuricals. The enzyme is a homodimeric protein with two interfacial active sites per dimer, which extensive evidence indicates sense the redox and/or ligand state of each other. We have recently found that in the oxidative half-reaction of the enzyme with bulky thiol-liganded Hg(II) compounds, comparable to the in vivo substrate, intersubunit interactions appear to be critical in the catalytic cycle while simpler Hg(II) compounds can bypass the normal entry route and the corresponding intersubunit interactions. We use MidasPlus to identify proposed entry pathways for the small verses large Hg(II) substrates and are currently using the software to aid in the identification of additional residues along these pathways that may participate in the ligand exchange processes and represent targets for mutational analysis. We are also using the software to help visualize the electrostatic potential of the protein, especially as the liganded or redox state changes with the hypothesis that this may be a key element in the intersubunit communication. A new direction that we plan to pursue is a reengineering of the metal ion specificity of the enzyme. With our recent identification of pathways for binding, we will use the graphics to consider what types of metal ion complexes we might be able to accomodate and what changes to make to accomplish the task.

汞离子还原酶催化双电子还原