Increased activity of porcine pancreatic phospholipase A2 by designed long-range electrostatic stabilisation of the transition state

Peter J. Sheffield; K. Mahalingeshwara Bhat; A. Jane Owen; Barry Perry; Ian G. Sumner; James Warwicker

doi:10.1006/bbrc.1995.2689

Increased activity of porcine pancreatic phospholipase A2 by designed long-range electrostatic stabilisation of the transition state

Peter J. Sheffield, K. Mahalingeshwara Bhat, A. Jane Owen, Barry Perry, Ian G. Sumner, James Warwicker

Research output: Contribution to journal › Article › peer-review

Abstract

Stabilisation of the catalytic transition state by long-range charge interactions has been tested with mutagenesis for porcine pancreatic phospholipase A2. Electrostatics calculations were used to determine locations which would interact preferentially with one part of the dipolar charge separation that is believed to develop in the transition state. Experiment shows increased enzyme activity relative to wild-type recombinant enzyme for mutants N97D and N101D, consistent with the design.

Original language	English
Pages (from-to)	778-784
Number of pages	6
Journal	Biochemical and Biophysical Research Communications
Volume	216
Issue number	3
DOIs	https://doi.org/10.1006/bbrc.1995.2689
Publication status	Published - 1995

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title = "Increased activity of porcine pancreatic phospholipase A2 by designed long-range electrostatic stabilisation of the transition state",

abstract = "Stabilisation of the catalytic transition state by long-range charge interactions has been tested with mutagenesis for porcine pancreatic phospholipase A2. Electrostatics calculations were used to determine locations which would interact preferentially with one part of the dipolar charge separation that is believed to develop in the transition state. Experiment shows increased enzyme activity relative to wild-type recombinant enzyme for mutants N97D and N101D, consistent with the design.",

author = "Sheffield, {Peter J.} and Bhat, {K. Mahalingeshwara} and Owen, {A. Jane} and Barry Perry and Sumner, {Ian G.} and James Warwicker",

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AU - Sheffield, Peter J.

AU - Bhat, K. Mahalingeshwara

AU - Owen, A. Jane

AU - Perry, Barry

AU - Sumner, Ian G.

AU - Warwicker, James

PY - 1995

Y1 - 1995

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AB - Stabilisation of the catalytic transition state by long-range charge interactions has been tested with mutagenesis for porcine pancreatic phospholipase A2. Electrostatics calculations were used to determine locations which would interact preferentially with one part of the dipolar charge separation that is believed to develop in the transition state. Experiment shows increased enzyme activity relative to wild-type recombinant enzyme for mutants N97D and N101D, consistent with the design.

U2 - 10.1006/bbrc.1995.2689

DO - 10.1006/bbrc.1995.2689

M3 - Article

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SN - 1090-2104

VL - 216

SP - 778

EP - 784

JO - Biochemical and Biophysical Research Communications

JF - Biochemical and Biophysical Research Communications

IS - 3

ER -

Increased activity of porcine pancreatic phospholipase A2 by designed long-range electrostatic stabilisation of the transition state

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