Ureases are moonlighting proteins displaying non-catalytic properties, including platelet activation, antifungal and entomotoxic effects. The structure-activity mapping of these properties is poorly developed. Proteus mirabilis urease (PMU) consists of three subunits, PmUreα, PmUreβ and PmUreγ, in an (αβγ)₃ organization. In order to study the structure-activity relationships of PMU we obtained the recombinant subunits of this urease and evaluated their biological activities. The holo-urease promoted platelet aggregation, and toxicity in fungal and insect models. Similar to Jaburetox, a plant urease-derived polypeptide, PmUreβ showed the highest toxicity against yeasts and insects, and activated human platelets. PmUreγ and PmUreα presented insecticidal action upon injection. In addition, only PmUreγ and PmUreβ promote hemocytes aggregation. Bioinformatics analyses revealed gene/segment duplication and evolutionary divergence among ureases. Our findings show that PmUreβ (and probably its counterparts in other ureases) carries most of the non-enzymatic activities of these proteins.

脲酶是具有非催化特性的兼职蛋白质，包括血小板活化、抗真菌和昆虫毒性作用。这些特性的结构-活性映射还很差。奇异变形杆菌脲酶 (PMU) 由三个亚基 PmUreα、PmUreβ 和 PmUreγ 组成，在 (αβγ) ₃组织。为了研究PMU的构效关系，我们获得了该脲酶的重组亚基并评估了它们的生物活性。全息脲酶促进血小板聚集，并在真菌和昆虫模型中产生毒性。与植物脲酶衍生多肽 Jaburetox 类似，PmUreβ 对酵母菌和昆虫表现出最高的毒性，并能激活人类血小板。PmUreγ 和 PmUreα 在注射后表现出杀虫作用。此外，只有 PmUreγ 和 PmUreβ 促进血细胞聚集。生物信息学分析揭示了脲酶之间的基因/片段重复和进化差异。我们的研究结果表明 PmUreβ（可能还有其他脲酶中的对应物）携带这些蛋白质的大部分非酶活性。