The First Hospital of Shanxi Medical University, Taiyuan, 030001, Shanxi, China; Department of Biochemistry and Molecular Biology, Shanxi Key Laboratory of Birth Defect and Cell Regeneration, Key Laboratory for Cellular Physiology of Ministry of Education, Shanxi Medical University, Taiyuan, 030001, Shanxi, China.
Department of Biochemistry and Molecular Biology, Shanxi Key Laboratory of Birth Defect and Cell Regeneration, Key Laboratory for Cellular Physiology of Ministry of Education, Shanxi Medical University, Taiyuan, 030001, Shanxi, China.
Biochem Biophys Res Commun. 2021 Jun 11;557:267-272. doi: 10.1016/j.bbrc.2021.04.030. Epub 2021 Apr 21.
Secreted phospholipase A2s (sPLA2s) are calcium dependent enzymes involved in various biological events such as lipid metabolism and inflammation. We previously identified the second calcium (Ca2) binding site of human sPLA2 Group IIE (hGIIE) by structural study and suggested that Asn21 act as the switch of Ca2 binding to modulate the enzymatic activity, but the detailed Ca2 binding mechanism is still unclear. Combined with enzymatic assay, model analysis and calcium binding affinity data for mutated hGIIE proteins, we herein further demonstrate that the flexibly bound Ca2 is essential for the catalysis of hGIIE, unlike the stable binding of Ca2 in hGIIA that replenishes the calcium in the typical loop during the reaction. The atypical Ca2 binding feature of hGIIE will provide a better understanding on the catalytic mechanism of hGIIE.
分泌型磷脂酶 A2（sPLA2s）是一种依赖于钙的酶，参与多种生物事件，如脂代谢和炎症。我们之前通过结构研究确定了人 sPLA2 组 IIE（hGIIE）的第二个钙（Ca2）结合位点，并提出天冬酰胺 21 作为 Ca2 结合的开关来调节酶活性，但 Ca2 结合的详细机制仍不清楚。结合酶活性测定、模型分析和突变 hGIIE 蛋白的钙结合亲和力数据，我们进一步证明，灵活结合的 Ca2 对于 hGIIE 的催化是必需的，与 hGIIA 中稳定结合的 Ca2 不同，后者在反应过程中补充典型环中的钙。hGIIE 的非典型 Ca2 结合特征将为 hGIIE 的催化机制提供更好的理解。
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