1FX9

CARBOXYLIC ESTER HYDROLASE COMPLEX (DIMERIC PLA2 + MJ33 INHIBITOR + SULPHATE IONS)

1FX9 の概要

• エントリーDOI: 10.2210/pdb1fx9/pdb
• 関連するPDBエントリー: 1FXF
• 分子名称: PHOSPHOLIPASE A2, MAJOR ISOENZYME, CALCIUM ION, SULFATE ION, ... (5 entities in total)
• 機能のキーワード: hydrolase, enzyme, carboxylic ester hydrolase, dimer, sulphate binding, inhibitor binding
• 由来する生物種: Sus scrofa (pig)
• 細胞内の位置: Secreted: P00592
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 29072.45

構造登録者

Pan, Y.H.,Epstein, T.M.,Jain, M.K.,Bahnson, B.J. (登録日: 2000-09-25, 公開日: 2001-09-25, 最終更新日: 2024-11-13)

主引用文献

Pan, Y.H.,Epstein, T.M.,Jain, M.K.,Bahnson, B.J.
Five coplanar anion binding sites on one face of phospholipase A2: relationship to interface binding.
Biochemistry, 40:609-617, 2001

PubMed Abstract: We report the structures of the crystallographic dimer of porcine pancreatic IB phospholipase A(2) (PLA2) with either five sulfate or phosphate anions bound. In each structure, one molecule of a tetrahedral mimic MJ33 [1-hexadecyl-3-(trifluoroethyl)-sn-glycero-2-phosphomethanol] and the five anions are shared between the two subunits of the dimer. The sn-2-phosphate of MJ33 is bound in the active site of one subunit (A), and the alkyl chain extends into the active site slot of the second subunit (B) across the subunit-subunit interface. The two subunits are packed together with a large hydrophobic and desolvated surface buried between them along with the five anions that define a plane. The anions bind by direct contact with two cationic residues (R6 and K10) per subunit and through closer-range H-bonding interactions with other polarizable ligands. These features of the "dimer" suggest that the binding of PLA2 to the anionic groups at the anionic interface may be dominated by coordination through H-bonding with only a partial charge compensation needed. Remarkably, the plane defined by the contact surface is similar to the i-face of the enzyme [Ramirez, F., and Jain, M. K. (1991) Proteins: Struct., Funct., Genet. 9, 229-239], which has been proposed to make contact with the substrate interface for the interfacial catalytic turnover. Additionally, these structures not only offer a view of the active PLA2 complexed to an anionic interface but also provide insight into the environment of the tetrahedral intermediate in the rate-limiting chemical step of the turnover cycle. Taken together, our results offer an atomic-resolution structural view of the i-face interactions of the active form of PLA2 associated to an anionic interface.

PubMed: 11170377
DOI: 10.1021/bi002514g

実験手法

X-RAY DIFFRACTION (2 Å)