BNLMS, State Key Laboratory of Structural Chemistry for Unstable and Stable Species, College of Chemistry and Molecular Engineering, Beijing 100871, China.
BNLMS, State Key Laboratory of Structural Chemistry for Unstable and Stable Species, College of Chemistry and Molecular Engineering, Beijing 100871, China; Center for Quantitative Biology, Peking University, Beijing 100871, China.
Biochem Biophys Res Commun. 2013 Nov 15;441(2):453-6. doi: 10.1016/j.bbrc.2013.10.092. Epub 2013 Oct 26.
Human non-pancreatic secretory phospholipase A2 (hnpsPLA2) is a group IIA phospholipase A2 which plays an important role in the innate immune response. This enzyme was found to exhibit bactericidal activity toward Gram-positive bacteria, but not Gram-negative ones. Though native hnpsPLA2 is active over a broad pH range, it is only highly active at alkaline conditions with the optimum activity pH of about 8.5. In order to make it highly active at neutral pH, we have obtained two hnpsPLA2 mutants, Glu89Lys and Arg100Glu that work better at neutral pH in a previous study. In the present study, we tested the bactericidal effects of the native hnpsPLA2 and the two mutants. Both native hnpsPLA2 and the two mutants exhibit bactericidal activity toward Gram-positive bacteria. Furthermore, they can also kill Escherichia coli, a Gram-negative bacterium. The two mutants showed better bactericidal activity for E. coli at neutral pH than the native enzyme, which is consistent with the enzyme activities. As hnpsPLA2 is highly stable and biocompatible, it may provide a promising therapy for bacteria infection treatment or other bactericidal applications.
人源非胰腺分泌型磷脂酶 A2（hnpsPLA2）是 IIA 组磷脂酶 A2，在先天免疫反应中发挥重要作用。该酶被发现对革兰氏阳性菌具有杀菌活性，但对革兰氏阴性菌没有。尽管天然 hnpsPLA2 在较宽的 pH 范围内具有活性，但它仅在碱性条件下高度活跃，最佳活性 pH 约为 8.5。为了使其在中性 pH 下具有高活性，我们在之前的研究中获得了两个 hnpsPLA2 突变体，Glu89Lys 和 Arg100Glu，它们在中性 pH 下的活性更好。在本研究中，我们测试了天然 hnpsPLA2 和两种突变体的杀菌效果。天然 hnpsPLA2 和两种突变体均对革兰氏阳性菌表现出杀菌活性。此外，它们还可以杀死革兰氏阴性菌大肠杆菌。与天然酶相比，两种突变体在中性 pH 下对大肠杆菌的杀菌活性更好，这与酶活性一致。由于 hnpsPLA2 具有高度稳定性和生物相容性，它可能为细菌感染治疗或其他杀菌应用提供有前途的治疗方法。
