PLP DEGRADATION

PLP降解

• 批准号: 8361600
• 负责人: STEVEN E EALICK
• 金额: $ 0.02万
• 依托单位: CORNELL UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-04-01 至 2012-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8361600
• 关键词: Acetates; Active Sites; Amino Acids; Ammonia; Anabolism; Bacteria; Binding; Carbon Dioxide; Carboxylic Acids; Complex; Decarboxylation; Diet; Electrons; Enzymes; Funding; Genes; Grant; Human; Hydrolase; Hydrolysis; Ligands; Lysine; Metabolism; National Center for Research Resources; Pathway interactions; Principal Investigator; Proteins; Publishing; Pyridoxal; Reaction; Research; Research Infrastructure; Resources; Source; Structure; Succinates; United States National Institutes of Health; Vitamin B6; Vitamins; Work; carbanion; cofactor; cost; enzyme pathway; enzyme substrate; hydroxypyridine; inorganic phosphate; racemization; structural biology; succinic semialdehyde; transamination

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Vitamin B6, the active cofactor of which is pyridoxal 52-phosphate (PLP), is an essential vitamin in the human diet. PLP is typically covalently bound to a PLP-dependent enzyme via an active site lysine until the substrate of that enzyme binds, when PLP is transferred to that ligand. PLP acts as an electron sink and helps to stabilize carbanion intermediates. This cofactor is known to be important in amino acid metabolism, and takes part in decarboxylation, transamination, and racemization reactions. Many structures are available of enzymes with PLP bound, and the structural biology of the biosynthesis of PLP has also been thoroughly studied. The degradation of PLP has been less well studied. Recently, the bacterium Mesorhizobium loti MAFF303099 has been shown to possess a pathway for producing succinic semialdehyde, ammonia, acetate, and carbon dioxide from PLP. The genes responsible for each of the seven enzymes of this catabolic pathway have been identified and the gene products kinetically characterized. The enzyme that catalyzes the sixth step, the oxidative ring opening of 2-methyl-3-hydroxypyridine-5-carboxylic acid (MHPC) to produce E-2-(acetamidomethylene)succinate (E-2AMS), has been recently described. This enzyme is an FAD dependent enzyme, and the first of two structures has only FAD bound to 2.1 ¿. The second complex contains both FAD and MHPC to 2.1 ¿. This work has recently been published (McCulloch, 2009). The final enzyme of this pathway, E-2AMS hydrolase, is responsible for the hydrolysis of E-2AMS to produce ammonia, acetate, carbon dioxide, and succinic semialdehyde.

该子项目是利用资源的众多研究子项目之一 由 NIH/NCRR 资助的中心拨款提供 该子项目的主要支持。 并且子项目的主要研究者可能是由其他来源提供的， 包括其他 NIH 来源的子项目可能列出的总成本。 代表子项目使用的中心基础设施的估计数量， NCRR 赠款不直接向子项目或子项目工作人员提供资金。 维生素 B6 的活性辅因子是 52-磷酸吡哆醛 (PLP)，是人类饮食中的必需维生素，PLP 通常通过活性位点赖氨酸与 PLP 依赖性酶共价结合，直到该酶的底物结合。当 PLP 转移到该配体时，PLP 充当电子接收器并有助于稳定碳负离子中间体，已知该辅助因子在氨基酸代谢中很重要，并参与脱羧，与 PLP 结合的酶有许多结构，并且 PLP 生物合成的结构生物学也已得到深入研究。 最近，细菌 Mesorhizobium Loti MAFF303099 已被证明具有从 PLP 产生琥珀酸半醛、氨、乙酸和二氧化碳的途径，这些基因负责该酶的七种酶中的每一种。分解代谢途径已被鉴定，并且催化第六步氧化开环的基因产物已被动力学表征。最近描述了 2-甲基-3-羟基吡啶-5-羧酸 (MHPC) 产生 E-2-(乙酰氨基亚甲基)琥珀酸 (E-2AMS)，这种酶是一种 FAD 依赖性酶，也是两种酶中的第一种。结构只有 FAD 绑定到 2.1 ¿第二个复合物包含 FAD 和 MHPC 至 2.1 ¿这项工作最近已发表（McCulloch，2009）。该途径的最终酶 E-2AMS 水解酶负责 E-2AMS 的水解，产生氨、乙酸、二氧化碳和琥珀半醛。