Secreted phospholipases A2 (sPLA2) group IIE (GIIE) is involved in several biological events, such as lipid metabolism and possibly inflammation that may mainly depend on its catalytic reaction. We previously showed that Asn21 is a critical residue that contributes to the enzymatic activity of hGIIE, but the underlying mechanism is still not clear. Here, combined with crystal structures and mutagenesis studies of the Asn21Gly mutant, we demonstrate that Asn21 acts as a switch responsible for the calcium binding and the catalytic efficiency. Our results of the atypical feature of calcium binding in hGIIE not only provide clues to understand the molecular basis of its enzymatic activity and physiological function, but also confer improved specificity for potential inhibitor design of sPLA2.

分泌的磷脂酶A2（sPLA2）组IIE（GIIE）涉及多种生物学事件，例如脂质代谢和可能的炎症，这可能主要取决于其催化反应。我们以前表明，Asn21是有助于hGIIE酶促活性的关键残基，但其潜在机制仍不清楚。在这里，结合Asn21Gly突变体的晶体结构和诱变研究，我们证明Asn21充当负责钙结合和催化效率的开关。我们在hGIIE中钙结合的非典型特征的结果不仅为了解其酶活性和生理功能的分子基础提供了线索，而且还赋予了sPLA2潜在抑制剂设计更高的特异性。