Residue Asn21 acts as a switch for calcium binding to modulate the enzymatic activity of human phospholipase A2 group
Shulin Hou1, Yulong Zhang2, Jinxin Xu2
1State 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.
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.
More Related Videos
07:11Dissipative Microgravimetry to Study the Binding Dynamics of the Phospholipid Binding Protein Annexin A2 to Solid-supported Lipid Bilayers Using a Quartz Resonator
Published on: November 1, 2018
12:07Chemical Modification of the Tryptophan Residue in a Recombinant Ca2+-ATPase N-domain for Studying Tryptophan-ANS FRET
Published on: October 9, 2021
Related Concept Videos
Calmodulin-dependent Signaling
The Ca2+-CaM complex does not have enzymatic activity by itself. Instead, the complex binds downstream target proteins, including membrane proteins or enzymes,...
IP3/DAG Signaling Pathway
Phosphoinositides and PIPs
Different phosphoinositides are synthesized and recruited on the cytosolic face of the plasma membrane. The localization of specific phosphoinositides concentrated in separate membrane...
Ligand-Gated Ion Channel Receptor: Gating Mechanism
Lipids as Anchors
The carboxy-terminal of most of the prenylated proteins, such as Ras proteins, contains...
Phosphorylation
During phosphorylation, protein kinases transfer the terminal phosphate group of ATP to specific amino acid side chains of substrate proteins. Serine, threonine, and tyrosine are the most commonly...
