Substrate-enzyme interactions and catalytic mechanism in phospholipase C: a molecular modeling study using the GRID program.
Based on the high-resolution X-ray crystallographic structure of phospholipase C from Bacillus cereus, the orientation of the phosphatidylcholine substrate in the active site of the enzyme is proposed. The proposal is based on extensive calculations using the GRID program and molecular mechanics geometry relaxations. The substrate model has been constructed by successively placing phosphate, choline and diacylglycerol moieties in the positions indicated from GRID calculations. On the basis of the resulting orientation of a complete phosphatidylcholine molecule, we propose a mechanism for the hydrolysis of the substrate.
Byberg
J R
JR
Department of Organic Chemistry, Royal Danish School of Pharmacy, Copenhagen.
Jørgensen
F S
FS
Hansen
S
S
Hough
E
E
D001665:Binding Sites; D002384:Catalysis; D003198:Computer Simulation; D008958:Models, Molecular; D010100:Oxygen / Q000737:chemistry; D010710:Phosphates / Q000737:chemistry; D000644:Quaternary Ammonium Compounds / Q000737:chemistry; D012984:Software; D013379:Substrate Specificity; D010738:Type C Phospholipases / Q000737:chemistry / Q000378:metabolism*; D015032:Zinc / Q000378:metabolism
D010710:Phosphates; D000644:Quaternary Ammonium Compounds; D010738:Type C Phospholipases; C027917:tetramethylammonium; D015032:Zinc; D010100:Oxygen