Substrate-enzyme interactions and catalytic mechanism in phospholipase C: a molecular modeling study using the GRID program

J R Byberg; Flemming Steen Jørgensen; S Hansen; E Hough

doi:10.1002/prot.340120405

Substrate-enzyme interactions and catalytic mechanism in phospholipase C: a molecular modeling study using the GRID program

J R Byberg, Flemming Steen Jørgensen, S Hansen, E Hough

22 Citations (Scopus)

Abstract

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.

Original language	English
Journal	Proteins: Structure, Function, and Bioinformatics
Volume	12
Issue number	4
Pages (from-to)	331-8
Number of pages	8
ISSN	0887-3585
DOIs	https://doi.org/10.1002/prot.340120405
Publication status	Published - 1992

Keywords

Binding Sites
Catalysis
Computer Simulation
Models, Molecular
Oxygen
Phosphates
Quaternary Ammonium Compounds
Software
Substrate Specificity
Type C Phospholipases
Zinc

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10.1002/prot.340120405

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title = "Substrate-enzyme interactions and catalytic mechanism in phospholipase C: a molecular modeling study using the GRID program",

abstract = "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.",

keywords = "Binding Sites, Catalysis, Computer Simulation, Models, Molecular, Oxygen, Phosphates, Quaternary Ammonium Compounds, Software, Substrate Specificity, Type C Phospholipases, Zinc",

author = "Byberg, {J R} and J{\o}rgensen, {Flemming Steen} and S Hansen and E Hough",

year = "1992",

doi = "10.1002/prot.340120405",

language = "English",

volume = "12",

pages = "331--8",

journal = "Proteins: Structure, Function, and Bioinformatics",

issn = "0887-3585",

publisher = "JohnWiley & Sons, Inc.",

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TY - JOUR

T1 - Substrate-enzyme interactions and catalytic mechanism in phospholipase C

T2 - a molecular modeling study using the GRID program

AU - Byberg, J R

AU - Jørgensen, Flemming Steen

AU - Hansen, S

AU - Hough, E

PY - 1992

Y1 - 1992

N2 - 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.

AB - 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.

KW - Binding Sites

KW - Catalysis

KW - Computer Simulation

KW - Models, Molecular

KW - Oxygen

KW - Phosphates

KW - Quaternary Ammonium Compounds

KW - Software

KW - Substrate Specificity

KW - Type C Phospholipases

KW - Zinc

U2 - 10.1002/prot.340120405

DO - 10.1002/prot.340120405

M3 - Journal article

C2 - 1579567

SN - 0887-3585

VL - 12

SP - 331

EP - 338

JO - Proteins: Structure, Function, and Bioinformatics

JF - Proteins: Structure, Function, and Bioinformatics

IS - 4

ER -

Substrate-enzyme interactions and catalytic mechanism in phospholipase C: a molecular modeling study using the GRID program

Abstract

Keywords

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