Molecular Recognition Laboratory, Centro de Investigación Príncipe Felipe, Valencia, Spain.
Protein Sci. 2010 Mar;19(3):372-82. doi: 10.1002/pro.340.
Pyrroline-5-carboxylate synthase (P5CS) is a bifunctional enzyme that exhibits glutamate kinase (GK) and gamma-glutamyl phosphate reductase (GPR) activities. The enzyme is highly relevant in humans because it belongs to a combined route for the interconversion of glutamate, ornithine and proline. The deficiency of P5CS activity in humans is associated with a rare, inherited metabolic disease. It is well established that some bacteria and plants accumulate proline in response to osmotic stress. The alignment of P5CSs from different species and analysis of the solved structures of GK and GPR reveal high sequence and structural conservation. The information acquired from different mutant enzymes with increased osmotolerant properties, together with the position of the insertion found in the longer human isoform, permit the delimitation of the regulatory site of GK and P5CS and the proposal of a model of P5CS architecture. Additionally, the GK moiety of the human enzyme has been modeled and the known clinical mutations and polymorphisms have been mapped.
吡咯啉-5-羧酸合成酶（P5CS）是一种具有谷氨酸激酶（GK）和γ-谷氨酰磷酸还原酶（GPR）活性的双功能酶。该酶在人类中非常重要，因为它属于谷氨酸、鸟氨酸和脯氨酸相互转化的综合途径。人类中 P5CS 活性的缺乏与一种罕见的遗传性代谢疾病有关。众所周知，一些细菌和植物会在受到渗透胁迫时积累脯氨酸。不同物种的 P5CS 的比对以及 GK 和 GPR 结构的解析揭示了高度的序列和结构保守性。具有增强耐渗性特性的不同突变酶获得的信息，以及在较长的人类同工型中发现的插入位置，允许限定 GK 和 P5CS 的调节位点，并提出 P5CS 结构的模型。此外，还对人类酶的 GK 部分进行了建模，并对已知的临床突变和多态性进行了映射。
