1DJX

PHOSPHOINOSITIDE-SPECIFIC PHOSPHOLIPASE C-DELTA1 FROM RAT COMPLEXED WITH INOSITOL-1,4,5-TRISPHOSPHATE

1DJX の概要

• エントリーDOI: 10.2210/pdb1djx/pdb
• 分子名称: PHOSPHOINOSITIDE-SPECIFIC PHOSPHOLIPASE C, ISOZYME DELTA1, CALCIUM ION, ACETATE ION, ... (5 entities in total)
• 機能のキーワード: phosphoric diester hydrolase, hydrolase, lipid degradation, transducer, calcium-binding, phospholipase c, phosphoinositide-specific
• 由来する生物種: Rattus norvegicus (Norway rat)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 142267.62

構造登録者

Essen, L.-O.,Perisic, O.,Williams, R.L. (登録日: 1996-08-24, 公開日: 1997-07-07, 最終更新日: 2024-02-07)

主引用文献

Essen, L.O.,Perisic, O.,Katan, M.,Wu, Y.,Roberts, M.F.,Williams, R.L.
Structural mapping of the catalytic mechanism for a mammalian phosphoinositide-specific phospholipase C.
Biochemistry, 36:1704-1718, 1997

PubMed Abstract: The crystal structures of various ternary complexes of phosphoinositide-specific phospholipase C-delta 1 from rat with calcium and inositol phosphates have been determined at 2.30-2.95 A resolution. The inositol phosphates used in this study mimic the binding of substrates and the reaction intermediate and include D-myo-inositol-1,4,5-trisphosphate, D-myo-inositol-2,4, 5-trisphosphate. D-myo-inositol-4,5-bisphosphate, and D,1-myo-inositol-2-methylene-1,2-cyclićmonophosphonate. The complexes exhibit an almost invariant mode of binding in the active site, each fitting edge-on into the active site and interacting with both the enzyme and the catalytic calcium at the bottom of the active site. Most of the active site residues do not undergo conformational changes upon binding either calcium or inositol phosphates. The structures are consistent with bidentate liganding of the catalytic calcium to the inositol phosphate intermediate and transition state. The complexes suggest explanations for substrate preference, pH optima, and ratio of cyclic to acyclic reaction products. A reaction mechanism is derived that supports general acid/base catalysis in a sequential mechanism involving a cyclic phosphate intermediate and rules out a parallel mechanism where acyclic and cyclic products are simultaneously generated.

PubMed: 9048554
DOI: 10.1021/bi962512p

実験手法

X-RAY DIFFRACTION (2.3 Å)