果糖1,6-二磷酸醛缩酶是一种普遍存在的胞浆酶,可催化糖酵解的第四步。醛缩酶分为三类:I类,IA类,和II类;所有类别都具有相似的结构特征,但氨基酸同一性低。除了它们在碳水化合物代谢中的保守作用,已经报道醛缩酶执行许多非酶功能。在这里,我们回顾了这种经典酶的无数“月光”功能,其中许多都集中在它与一系列影响细胞支架的伴侣蛋白结合的能力上,信令,转录,和运动性。除了胞质位置,醛缩酶已被发现在几种致病菌的细胞外表面,真菌,原生动物,和后生动物。在细胞外空间,据报道,该酶具有增强毒力的月光功能,例如,纤溶酶原结合,宿主细胞粘附,和免疫调节。醛缩酶的重要性使其成为药物靶标和疫苗候选物。在这次审查中,我们注意到已经合成的几种抑制剂对病原体和癌细胞的醛缩酶具有高特异性,并且已经显示出抑制经典酶活性和月光功能。我们还回顾了许多试验,其中重组醛缩酶已被用作针对多种病原生物(包括细菌)的疫苗靶标。真菌,和后生寄生虫.大多数这样的试验对攻击感染产生了显著的保护作用,与抗原特异性细胞和体液免疫反应相关。我们认为,应鼓励醛缩酶抗原制剂的改进和免疫试验的扩大,以促进有希望的进展。保护性醛缩酶疫苗。
Fructose 1,6-bisphosphate aldolase is a ubiquitous cytosolic enzyme that catalyzes the fourth step of glycolysis. Aldolases are classified into three groups: Class-I, Class-IA, and Class-II; all classes share similar structural features but low amino acid identity. Apart from their conserved role in carbohydrate metabolism, aldolases have been reported to perform numerous non-enzymatic functions. Here we review the myriad \"moonlighting\" functions of this classical enzyme, many of which are centered on its ability to bind to an array of partner proteins that impact cellular scaffolding, signaling, transcription, and motility. In addition to the cytosolic location, aldolase has been found the extracellular surface of several pathogenic bacteria, fungi, protozoans, and metazoans. In the extracellular space, the enzyme has been reported to perform virulence-enhancing moonlighting functions e.g., plasminogen binding, host cell adhesion, and immunomodulation. Aldolase\'s importance has made it both a drug target and vaccine candidate. In this review, we note the several inhibitors that have been synthesized with high specificity for the aldolases of pathogens and cancer cells and have been shown to inhibit classical enzyme activity and moonlighting functions. We also review the many trials in which recombinant aldolases have been used as vaccine targets against a wide variety of pathogenic organisms including bacteria, fungi, and metazoan parasites. Most of such trials generated significant protection from challenge infection, correlated with antigen-specific cellular and humoral immune responses. We argue that refinement of aldolase antigen preparations and expansion of immunization trials should be encouraged to promote the advancement of promising, protective aldolase vaccines.