4QGD

Crystal Structure of the Complex of Phospholipase A2 with Gramine derivative at 1.80 A Resolution

4QGD の概要

• エントリーDOI: 10.2210/pdb4qgd/pdb
• 関連するPDBエントリー: 1FB2 4QEM 4QER 4QF7 4QF8
• 分子名称: Phospholipase A2 VRV-PL-VIIIa, 3-{3-[(DIMETHYLAMINO)METHYL]-1H-INDOL-7-YL}PROPAN-1-OL (3 entities in total)
• 機能のキーワード: hydrolase-hydrolase inhibitor complex, hydrolase/hydrolase inhibitor
• 由来する生物種: Daboia russellii pulchella
• 細胞内の位置: Secreted : D0VX11
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 13862.09

構造登録者

Shukla, P.K.,Sinha, M.,Kaur, P.,Sharma, S.,Singh, T.P. (登録日: 2014-05-22, 公開日: 2014-06-18, 最終更新日: 2024-10-30)

主引用文献

Shukla, P.K.,Gautam, L.,Sinha, M.,Kaur, P.,Sharma, S.,Singh, T.P.
Structures and binding studies of the complexes of phospholipase A2 with five inhibitors
Biochim.Biophys.Acta, 1854:269-277, 2015

PubMed Abstract: Phospholipase A2 (PLA2) catalyzes the hydrolysis of phospholipids into arachidonic acid and lysophospholipids. Arachidonic acid is used as a substrate in the next step of the multistep pathway leading to the production of eicosanoids. The eicosanoids, in extremely low concentrations, are required in a number of physiological processes. However, the increase in their concentrations above the essential physiological requirements leads to various inflammatory conditions. In order to prevent the unwanted rise in the concentrations of eicosanoids, the actions of PLA2 and other enzymes of the pathway need to be blocked. We report here the structures of five complexes of group IIA PLA2 from Daboia russelli pulchella with tightly binding inhibitors, (i) p-coumaric acid, (ii) resveratrol, (iii) spermidine, (iv) corticosterone and (v) gramine derivative. The binding studies using fluorescence spectroscopy and surface plasmon resonance techniques for the interactions of PLA2 with the above five compounds showed high binding affinities with values of dissociation constants (KD) ranging from 3.7×10(-8) M to 2.1×10(-9) M. The structure determinations of the complexes of PLA2 with the above five compounds showed that all the compounds bound to PLA2 in the substrate binding cleft. The protein residues that contributed to the interactions with these compounds included Leu2, Leu3, Phe5, Gly6, Ile9, Ala18, Ile19, Trp22, Ser23, Cys29, Gly30, Cys45, His48, Asp49 and Phe106. The positions of side chains of several residues including Leu2, Leu3, Ile19, Trp31, Lys69, Ser70 and Arg72 got significantly shifted while the positions of active site residues, His48, Asp49, Tyr52 and Asp99 were unperturbed.

PubMed: 25541253
DOI: 10.1016/j.bbapap.2014.12.017

実験手法

X-RAY DIFFRACTION (1.8 Å)