Probing UDP-glucuronosyltransferase protein-protein interactions: The power of two.

探索 UDP-葡萄糖醛酸基转移酶蛋白质-蛋白质相互作用：二的力量。

• 批准号: nhmrc : 426709
• 负责人: E/Pr Peter Mackenzie
• 金额: $ 32.19万
• 依托单位: Flinders University
• 依托单位国家: 澳大利亚
• 项目类别: NHMRC Project Grants
• 财政年份: 2007
• 资助国家: 澳大利亚
• 起止时间: 2007-01-01 至 2009-12-31
• 项目状态: 已结题
• 来源: https://researchdata.edu.au/probing-udp-glucuronosyltransferase-power-two/76051
• 关键词: Probing; UDP; glucuronosyltransferase; protein; interactions

Drugs and other chemicals (eg. dietary constituents, environmental pollutants, and chemicals that occur naturally in the body - such as steroid hormones) are broken down by specialised proteins called enzymes. This process is referred to as biotransformation, or 'metabolism'. Drug and chemical metabolism serves as a detoxification mechanism (since the products of metabolism generally lack biological activity) and as a means of eliminating these substances from the body. UDP-Glucuronosyltransferase (UGT) is one of the most important enzymes involved in drug and chemical metabolism. Consistent with its ability to metabolise such a large number of compounds, UGT is known to exist as a 'superfamily' of structurally related proteins. Despite the importance of UGT, little is known about the structural characteristics of these enzymes that are responsible for recognising and binding different classes of chemicals. Accumulating evidence from this and other laboratories indicates that the individual UGT proteins may combine with themselves (to form a homodimer) and with other UGT proteins (to form heterodimers). This project largely seeks to define the scope of UGT homo- and hetero- dimerisation, identify the structural elements of the proteins responsible for association and characterise the functional significance of dimerisation. The project will further explore associations between UGTs and other proteins, namely albumin. Characterisation of UGT dimerisation and associations with other proteins is fundamental to our understanding of how this enzyme functions and selects particular chemicals for metabolism. The work also has important implications for the devlopment and interpretation of in vitro (or 'test-tube') approaches for predicting how drugs are metabolised in humans. Such tests are widely employed in research and pharmaceutical company laboratories to predict how the body 'handles' new drugs prior to their administration to humans.

药物和其他化学物质（例如饮食成分、环境污染物和体内自然产生的化学物质，例如类固醇激素）会被称为酶的特殊蛋白质分解。这个过程称为生物转化或“新陈代谢”。药物和化学代谢是一种解毒机制（因为代谢产物通常缺乏生物活性），也是从体内消除这些物质的一种手段。 UDP-葡萄糖醛酸基转移酶（UGT）是参与药物和化学代谢的最重要的酶之一。与其代谢如此大量化合物的能力相一致，UGT 被认为是作为结构相关蛋白质的“超家族”存在。尽管 UGT 很重要，但人们对这些负责识别和结合不同类别化学物质的酶的结构特征知之甚少。从该实验室和其他实验室积累的证据表明，各个 UGT 蛋白可能与其自身结合（形成同二聚体），也可能与其他 UGT 蛋白结合（形成异二聚体）。该项目主要旨在定义UGT同源和异源二聚化的范围，识别负责关联的蛋白质的结构元件并表征二聚化的功能意义。该项目将进一步探索 UGT 与其他蛋白质（即白蛋白）之间的关联。 UGT 二聚化的表征以及与其他蛋白质的关联对于我们了解这种酶如何发挥作用以及选择特定化学物质进行代谢至关重要。这项工作对于预测药物在人体中如何代谢的体外（或“试管”）方法的开发和解释也具有重要意义。此类测试广泛应用于研究和制药公司实验室，以预测人体在向人类施用新药之前如何“处理”新药。