Hove-Jensen Bjarne, Andersen Kasper R, Kilstrup Mogens, Martinussen Jan, Switzer Robert L, Willemoës Martin
DTU Systems Biology, Technical University of Denmark, Kongens Lyngby, Denmark
Department of Molecular Biology and Genetics, Aarhus University, Aarhus, Denmark.
Microbiol Mol Biol Rev. 2016 Dec 28;81(1). doi: 10.1128/MMBR.00040-16. Print 2017 Mar.
Phosphoribosyl diphosphate (PRPP) is an important intermediate in cellular metabolism. PRPP is synthesized by PRPP synthase, as follows: ribose 5-phosphate + ATP → PRPP + AMP. PRPP is ubiquitously found in living organisms and is used in substitution reactions with the formation of glycosidic bonds. PRPP is utilized in the biosynthesis of purine and pyrimidine nucleotides, the amino acids histidine and tryptophan, the cofactors NAD and tetrahydromethanopterin, arabinosyl monophosphodecaprenol, and certain aminoglycoside antibiotics. The participation of PRPP in each of these metabolic pathways is reviewed. Central to the metabolism of PRPP is PRPP synthase, which has been studied from all kingdoms of life by classical mechanistic procedures. The results of these analyses are unified with recent progress in molecular enzymology and the elucidation of the three-dimensional structures of PRPP synthases from eubacteria, archaea, and humans. The structures and mechanisms of catalysis of the five diphosphoryltransferases are compared, as are those of selected enzymes of diphosphoryl transfer, phosphoryl transfer, and nucleotidyl transfer reactions. PRPP is used as a substrate by a large number phosphoribosyltransferases. The protein structures and reaction mechanisms of these phosphoribosyltransferases vary and demonstrate the versatility of PRPP as an intermediate in cellular physiology. PRPP synthases appear to have originated from a phosphoribosyltransferase during evolution, as demonstrated by phylogenetic analysis. PRPP, furthermore, is an effector molecule of purine and pyrimidine nucleotide biosynthesis, either by binding to PurR or PyrR regulatory proteins or as an allosteric activator of carbamoylphosphate synthetase. Genetic analyses have disclosed a number of mutants altered in the PRPP synthase-specifying genes in humans as well as bacterial species.
磷酸核糖焦磷酸（PRPP）是细胞代谢中的一种重要中间体。PRPP由PRPP合酶合成，反应如下：5-磷酸核糖 + ATP → PRPP + AMP。PRPP在生物体内广泛存在，并用于糖苷键形成的取代反应。PRPP用于嘌呤和嘧啶核苷酸、氨基酸组氨酸和色氨酸、辅因子NAD和四氢甲蝶呤、阿拉伯糖基单磷酸十聚戊烯醇以及某些氨基糖苷类抗生素的生物合成。本文综述了PRPP在这些代谢途径中的参与情况。PRPP代谢的核心是PRPP合酶，已通过经典的机制方法对来自所有生命王国的该酶进行了研究。这些分析结果与分子酶学的最新进展以及对真细菌、古细菌和人类PRPP合酶三维结构的阐明相结合。比较了五种二磷酸转移酶的催化结构和机制，以及二磷酸转移、磷酸转移和核苷酸转移反应中选定酶的结构和机制。大量磷酸核糖转移酶将PRPP用作底物。这些磷酸核糖转移酶的蛋白质结构和反应机制各不相同，证明了PRPP作为细胞生理学中间体的多功能性。系统发育分析表明，PRPP合酶在进化过程中似乎起源于一种磷酸核糖转移酶。此外，PRPP是嘌呤和嘧啶核苷酸生物合成的效应分子，它可以通过与PurR或PyrR调节蛋白结合，或者作为氨甲酰磷酸合成酶的变构激活剂发挥作用。遗传分析已经揭示了人类以及细菌物种中许多PRPP合酶指定基因发生改变的突变体。
