5Y5E

Crystal structure of phospholipase A2 with inhibitor

Summary for 5Y5E

• Entry DOI: 10.2210/pdb5y5e/pdb
• Descriptor: Group IIE secretory phospholipase A2, GLYCEROL, 2-[2-methyl-3-oxamoyl-1-[[2-(trifluoromethyl)phenyl]methyl]indol-4-yl]oxyethanoic acid, ... (8 entities in total)
• Functional Keywords: mutant, hydrolase-inhibitor complex, hydrolase/inhibitor
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 1
• Total formula weight: 14978.21

Authors

Hou, S.,Xu, J.,Xu, T.,Liu, J. (deposition date: 2017-08-08, release date: 2018-06-20, Last modification date: 2024-10-23)

Primary citation

Hou, S.,Xu, T.,Xu, J.,Qu, L.,Xu, Y.,Chen, L.,Liu, J.
Structural basis for functional selectivity and ligand recognition revealed by crystal structures of human secreted phospholipase A2group IIE
Sci Rep, 7:10815-10815, 2017

PubMed Abstract: Secreted phospholipases As (sPLAs) are involved in various pathological conditions such as rheumatoid arthritis and cardiovascular disease. Many inhibitors were developed and studied in clinical trials, but none have reached the market yet. This failure may be attributed to the lack of subtype selectivity for these inhibitors. Therefore, more structural information for subtype sPLA is needed to guide the selective inhibitor development. In this study, the crystal structure of human sPLA Group IIE (hGIIE), coupled with mutagenesis experiments, proved that the flexible second calcium binding site and residue Asn21 in hGIIE are essential to its enzymatic activity. Five inhibitor bound hGIIE complex structures revealed the key residues (Asn21 and Gly6) of hGIIE that are responsible for interacting with inhibitors, and illustrated the difference in the inhibitor binding pocket with other sPLAs. This will facilitate the structure-based design of sPLA's selective inhibitors.

PubMed: 28883454
DOI: 10.1038/s41598-017-11219-8

Experimental method

X-RAY DIFFRACTION (1.8 Å)