5WZV

Crystal structure of human secreted phospholipase A2 group IIE with Me-indoxam

5WZV の概要

• エントリーDOI: 10.2210/pdb5wzv/pdb
• 関連するPDBエントリー: 5WZM 5WZO 5WZS 5WZT 5WZU 5WZW
• 分子名称: Group IIE secretory phospholipase A2, CALCIUM ION, 2-[2-methyl-3-oxamoyl-1-[(2-phenylphenyl)methyl]indol-4-yl]oxyethanoic acid, ... (7 entities in total)
• 機能のキーワード: phospholipase a2, inhibitor, hydrolase-inhibitor complex, hydrolase/inhibitor
• 由来する生物種: Homo sapiens (Human)
• 細胞内の位置: Secreted: Q9NZK7
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 14801.91

構造登録者

Hou, S.,Xu, J.,Xu, T.,Liu, J. (登録日: 2017-01-18, 公開日: 2018-01-24, 最終更新日: 2024-10-16)

主引用文献

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 A2 group 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

実験手法

X-RAY DIFFRACTION (2.2 Å)