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.

这个子项目是利用资源的许多研究子项目之一。 由NIH/NCRR资助的中心拨款提供。对子项目的主要支持 子项目的首席调查员可能是由其他来源提供的， 包括美国国立卫生研究院的其他来源。为子项目列出的总成本可能 表示该子项目使用的中心基础设施的估计数量， 不是由NCRR赠款提供给次级项目或次级项目工作人员的直接资金。 维生素B6是人体必需的维生素，其活性辅因子为52-磷酸吡哆醛(PLP)。PLP通常通过活性部位赖氨酸共价结合到PLP依赖的酶上，直到该酶的底物结合，当PLP转移到该配体上时。PLP起电子接收器的作用，有助于稳定碳负离子中间体。这种辅因子在氨基酸新陈代谢中起重要作用，并参与脱羧基、转氨基和消旋反应。与PLP结合的酶有多种结构，PLP生物合成的结构生物学也得到了深入的研究。 PLP的降解还没有得到很好的研究。最近，中生根瘤菌MAFF303099被证明具有从PLP产生丁二酸半醛、氨、乙酸酯和二氧化碳的途径。负责这一分解代谢途径的七种酶的基因已经确定，并对基因产物进行了动力学表征。催化第六步2-甲基-3-羟基吡啶-5-羧酸(MHPC)氧化开环生成E-2-(乙酰亚甲基)丁二酸酯(E-2AMS)的酶最近被报道。这种酶是一种依赖于FAD的酶，两种结构中的第一种只与FAD结合。第二个复合体含有FAD和MHPC至2.1°。这项工作最近出版了(McCulloch，2009)。这个途径的最后一种酶，E-2AMS水解酶，负责E-2AMS的水解酶，以产生氨、乙酸酯、二氧化碳和丁二酸半醛。