Academic Journal
Structural Mapping of the Catalytic Mechanism for a Mammalian
| العنوان: | Structural Mapping of the Catalytic Mechanism for a Mammalian |
|---|---|
| المؤلفون: | Phosphoinositide-specific Phospholipase C, Lars-oliver Essen, Olga Perisic, Matilda Katan, Yiqin Wu, Mary F. Roberts, Roger L. Williams |
| المساهمون: | The Pennsylvania State University CiteSeerX Archives |
| المصدر: | http://www.mrc-lmb.cam.ac.uk/rlw/text/pdffiles/9048554.pdf. |
| سنة النشر: | 1996 |
| المجموعة: | CiteSeerX |
| الوصف: | C-δ1 from rat with calcium and inositol phosphates have been determined at 2.30-2.95 Å 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-4,5bisphosphate, and D,L-myo-inositol-2-methylene-1,2-cyclicmonophosphonate. 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. Mammalian phosphoinositide-specific phospholipases C (PI-PLC, EC 3.1.4.11) 1 catalyze hydrolysis of phosphatidylinositol-4,5-bisphosphate (PIP2) toD-myo-inositol-1,4,5trisphosphate |
| نوع الوثيقة: | text |
| وصف الملف: | application/pdf |
| اللغة: | English |
| Relation: | http://citeseerx.ist.psu.edu/viewdoc/summary?doi=10.1.1.326.4983; http://www.mrc-lmb.cam.ac.uk/rlw/text/pdffiles/9048554.pdf |
| الاتاحة: | http://citeseerx.ist.psu.edu/viewdoc/summary?doi=10.1.1.326.4983 http://www.mrc-lmb.cam.ac.uk/rlw/text/pdffiles/9048554.pdf |
| Rights: | Metadata may be used without restrictions as long as the oai identifier remains attached to it. |
| رقم الانضمام: | edsbas.B16E6A5B |
| قاعدة البيانات: | BASE |
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