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.

该副本是利用资源的众多研究子项目之一 由NIH/NCRR资助的中心赠款提供。对该子弹的主要支持 而且，副投影的主要研究员可能是其他来源提供的 包括其他NIH来源。列出的总费用可能 代表subproject使用的中心基础架构的估计量， NCRR赠款不直接向子弹或副本人员提供的直接资金。 维生素B6，其活性辅助因子是52-磷酸吡啶毒素（PLP），是人类饮食中必不可少的维生素。 PLP通常通过活性位点赖氨酸共价与PLP依赖性酶结合，直到将PLP转移到该配体中时该酶的底物结合。 PLP充当电子水槽，有助于稳定碳化中间体。该辅助因子在氨基酸代谢中很重要，并参与脱羧，跨动力和种族化反应。许多结构都可以使用具有PLP结合的酶，并且PLP的生物合成的结构生物学也已被彻底研究。 PLP的降解效果不佳。最近，已显示细菌loti maff303099具有产生PLP中产生琥珀酸半二氢，氨，乙酸和二氧化碳的途径。已经鉴定出了该分解代谢途径的七种酶中每种酶的基因，并具有动力学表征的基因产物。最近已经描述了催化第六步的酶，即2-甲基-3-羟基吡啶-5-羧酸（MHPC）的氧化环开口，以产生E-2-（乙酰氨基甲基）琥珀酸（E-2AMS）。该酶是一种依赖性的酶，两个结构中的第一个仅为2.1€。第二种配合物均包含FAD和MHPC为2.1。这项工作最近发表（McCulloch，2009）。该途径的最终酶E-2AMS水解酶负责E-2AMS的水解生产氨，乙酸，二氧化碳和琥珀酸半二氧化碳。