Residue Asn21 acts as a switch for calcium binding to modulate the enzymatic activity of human phospholipase A2 group IIE

Shulin Hou; Yulong Zhang; Jinxin Xu; Junping Bai; Jinsong Liu; Jun Xie; Tingting Xu

doi:10.1016/j.biochi.2020.07.003

Residue Asn21 acts as a switch for calcium binding to modulate the enzymatic activity of human phospholipase A2 group IIE

Biochimie. 2020 Sep:176:117-121. doi: 10.1016/j.biochi.2020.07.003. Epub 2020 Jul 10.

Authors

Shulin Hou¹, Yulong Zhang², Jinxin Xu², Junping Bai³, Jinsong Liu², Jun Xie⁴, Tingting Xu⁵

Affiliations

¹ State Key Laboratory of Respiratory Disease, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, 510530, China; Department of Biochemistry and Molecular Biology, Shanxi Key Laboratory of Birth Defect and Cell Regeneration, Shanxi Medical University, Taiyuan, 030001, Shanxi, China.
² State Key Laboratory of Respiratory Disease, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, 510530, China; Guangdong Provincial Key Laboratory of Biocomputing, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, 510530, China.
³ Department of Biochemistry and Molecular Biology, Shanxi Key Laboratory of Birth Defect and Cell Regeneration, Shanxi Medical University, Taiyuan, 030001, Shanxi, China.
⁴ Department of Biochemistry and Molecular Biology, Shanxi Key Laboratory of Birth Defect and Cell Regeneration, Shanxi Medical University, Taiyuan, 030001, Shanxi, China. Electronic address: junxie@sxmu.edu.cn.
⁵ State Key Laboratory of Respiratory Disease, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, 510530, China; Guangdong Provincial Key Laboratory of Biocomputing, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, 510530, China. Electronic address: xu_tingting@gibh.ac.cn.

PMID: 32659444
DOI: 10.1016/j.biochi.2020.07.003

Abstract

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.

Keywords: Calcium binding; Catalytic efficiency; Mutation; Phospholipase A2.

MeSH terms

Amino Acid Substitution
Asparagine / chemistry
Asparagine / genetics
Calcium / chemistry*
Group II Phospholipases A2 / chemistry*
Group II Phospholipases A2 / genetics
Humans
Mutation, Missense
Protein Binding

Substances

Asparagine
Group II Phospholipases A2
Calcium