1DJZ

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

Summary for 1DJZ

• Entry DOI: 10.2210/pdb1djz/pdb
• Descriptor: PHOSPHOINOSITIDE-SPECIFIC PHOSPHOLIPASE C, ISOZYME DELTA1, CALCIUM ION, ACETATE ION, ... (5 entities in total)
• Functional Keywords: phosphoric diester hydrolase, hydrolase, lipid degradation, transducer, calcium-binding, phospholipase c, phosphoinositide-specific
• Biological source: Rattus norvegicus (Norway rat)
• Total number of polymer chains: 2
• Total formula weight: 142107.66

Authors

Essen, L.-O.,Perisic, O.,Williams, R.L. (deposition date: 1996-08-24, release date: 1997-07-07, Last modification date: 2024-02-07)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (2.95 Å)