PMID: 2116905Jun 26, 1990Paper

Activities of native and tyrosine-69 mutant phospholipases A2 on phospholipid analogues. A reevaluation of the minimal substrate requirements

Biochemistry
O P KuipersG H de Haas

Abstract

The role of Tyr-69 of porcine pancreatic phospholipase A2 in substrate binding was studied with the help of proteins modified by site-directed mutagenesis and phospholipid analogues with a changed head-group geometry. Two mutants were used containing Phe and Lys, respectively, at position 69. Modifications in the phospholipids included introduction of a sulfur at the phosphorus (thionophospholipids), removal of the negative charge at phosphorus (phosphatidic acid dimethyl ester), and reduction (phosphonolipids) or extension (diacylbutanetriol choline phosphate) of the distance between the phosphorus and the acyl ester bond. Replacement of Tyr-69 by Lys reduces enzymatic activity, but the mutant enzyme retains both the stereospecificity and positional specificity of native phospholipase A2. The Phe-69 mutant not only hydrolyzes the Rp isomer of thionophospholipids more efficiently than the wild-type enzyme, but the Sp thiono isomer is hydrolyzed too, although at a low (approximately 4%) rate. Phosphonolipids are hydrolyzed by native phospholipase A2 about 7 times more slowly than natural phospholipids, with retention of positional specificity and a (partial) loss of stereospecificity. The dimethyl ester of phosphatidic acid is d...Continue Reading

References

Jan 1, 1976·Annual Review of Biophysics and Bioengineering·R Verger
Apr 24, 1968·Biochimica Et Biophysica Acta·G H de HaasL L van Deenen
Apr 1, 1972·Chemistry and Physics of Lipids·P P BonsenL L Van Deenen
Dec 21, 1984·Nucleic Acids Research·W KramerH J Fritz
Jan 1, 1984·Molecular & General Genetics : MGG·E T Palva, T J Silhavy
May 10, 1983·Biochemistry·G M Donné-Op den KelderM R Egmond
Sep 25, 1982·Journal of Molecular Biology·D C Rees, W N Lipscomb

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Citations

Jun 25, 2013·Journal of Molecular Modeling·Gururao HariprasadReema Singh
Nov 26, 1999·Biochimica Et Biophysica Acta·C Yuan, M Tsai
Mar 28, 1991·European Journal of Biochemistry·A VandermeersJ Christophe
Mar 10, 1995·The Journal of Biological Chemistry·G LambeauM Lazdunski
Dec 26, 2001·Chemical Reviews·O G BergM K Jain
Mar 24, 2009·Biochemistry·Bao-Zhu YuMahendra K Jain

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