PLP DEGRADATION

这个子项目是许多利用资源的研究子项目之一 由NIH/NCRR资助的中心拨款提供。子项目的主要支持 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。 为子项目列出的总成本可能 表示子项目使用的中心基础设施的估计数量， 而不是由NCRR赠款提供给子项目或子项目工作人员的直接资金。 维生素B6，其活性辅因子是吡哆醛52-磷酸（PLP），是人类饮食中的必需维生素。 PLP通常经由活性位点赖氨酸共价结合至PLP依赖性酶，直到当PLP转移至该配体时该酶的底物结合。 PLP作为电子阱，有助于稳定碳负离子中间体。 已知这种辅因子在氨基酸代谢中是重要的，并且参与脱羧、转氨和外消旋反应。 与PLP结合的酶的结构多种多样，PLP生物合成的结构生物学也得到了深入的研究。 PLP的降解研究较少。 最近，已显示细菌中慢生根瘤菌（Mesorhizobium loti）MAFF 303099具有从PLP产生琥珀酸半醛、氨、乙酸盐和二氧化碳的途径。 负责这一分解代谢途径的七种酶中每一种的基因已经被鉴定，基因产物的动力学特征也已被确定。 催化第六步，2-甲基-3-羟基吡啶-5-羧酸（MHPC）氧化开环产生E-2-（乙酰氨基亚甲基）琥珀酸酯（E-2AMS）的酶最近已被描述。 这种酶是一种FAD依赖性酶，两种结构中的第一种只有FAD与2.1？结合。 第二个复合物包含FAD和MHPC至2.1 ½。 这项工作最近发表（McCulloch，2009）。 该途径的最后一种酶E-2AMS水解酶负责水解E-2AMS以产生氨、乙酸盐、二氧化碳和琥珀酸半醛。

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.