ENZYMES OF QUINOLINIC ACID BIOSYNTHESIS

喹啉酸生物合成酶

• 批准号: 7369478
• 负责人: STEVEN E EALICK
• 金额: $ 0.1万
• 依托单位: CORNELL UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-06-01 至 2007-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7369478
• 关键词: ENZYMES; QUINOLINIC; ACID; BIOSYNTHESIS

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Quinolinic acid is the de novo precursor to the pyridine ring of nicotinamide adenine dinucleotide (NAD), an essential redox cofactor in all living systems. There are two different biosynthetic pathways to quinolinic acid. In prokaryotes, quinolinic acid is mostly formed from aspartate and dihydroxyacetone phosphate; in eukaryotes, it is formed from tryptophan. However, a tryptophan based pathway has been recently identified in bacteria. Our goal is to structurally characterize the enzymes in both pathways to help our understanding of the enzymatic mechanism. In the tryptophan based pathway, our targets are 2,3-tryptophan dioxygenase (TDO), which is the first enzyme in the pathway converting tryptophan to N-formyl kynurenine, and 3-hydroxyanthranilate-3,4-dioxygenase (HAD), which is the last enzyme oxidizing 3-hydroxyanthranilate to yield quinolinic acid. In the aspartate based pathway, our focus is on the prokaryotic enzyme quinolinate synthase (QS), which catalyzes the condensation of iminoaspartate and dihydroxyacetone phosphate to form quinolinic acid. This is the last enzyme in this pathway to be structurally and biochemically characterized.

该子项目是利用NIH/NCRR资助的中心赠款提供的资源的许多研究子项目之一。子项目和研究者（PI）可能从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。所列机构为中心，不一定是研究者所在机构。喹啉酸是烟酰胺腺嘌呤二核苷酸（NAD）吡啶环的从头前体，NAD是所有生命系统中必不可少的氧化还原辅因子。喹啉酸有两种不同的生物合成途径。在原核生物中，喹啉酸主要由天冬氨酸和磷酸二羟丙酮形成;在真核生物中，它由色氨酸形成。然而，最近已经在细菌中鉴定了基于色氨酸的途径。我们的目标是从结构上表征这两种途径中的酶，以帮助我们理解酶促机制。在基于色氨酸的途径中，我们的靶标是2，3_色氨酸双加氧酶（TDO），其是将色氨酸转化为N-甲酰基犬尿氨酸的途径中的第一个酶，以及3-羟基邻氨基苯甲酸-3，4-双加氧酶（HAD），其是氧化3-羟基邻氨基苯甲酸以产生喹啉酸的最后一个酶。在基于天冬氨酸的途径中，我们的重点是原核酶喹啉合酶（QS），它催化亚氨基天冬氨酸和磷酸二羟丙酮缩合形成喹啉酸。这是该途径中最后一种需要进行结构和生化表征的酶。