Journal article


The mode of action of phospholipase A(2): Semiempirical MO calculations including the protein environment


Publication Details
Author(s): Schürer G, Lanig H, Clark T
Publisher: American Chemical Society
Publication year: 2000
Volume: 104
Journal issue: 6
Pages range: 1349-1361
ISSN: 1520-6106
eISSN: 1520-5207

Abstract

Phospholipase A(2) is a calcium-dependent enzyme involved in inflammatory processes by releasing arachidonic acid from the sn-2 position of phosphatidyl-cholines. The catalyzed reaction is an ester hydrolysis that takes place in two proton transfer steps via an intermediate. Two mechanisms, which differ mainly in the rate-limiting step, have been proposed in the literature. The reaction has been calculated semiempirically (PM3) for a protein fragment containing the active site (156 atoms). To take long-range electrostatic interactions of the protein bulk with the active site into account, a classical-mechanical protein environment has been provided by a rigid point-charge array with associated van der Waals potentials. In this way a model system has been built that simulates the natural situation in an enzyme more realistically than a pure model of the active site. A comparison between the relative energy paths obtained by calculating the reaction in the isolated active site and within the classical mechanical environment shows that the long-range interactions have a strong influence on the mechanism. While the calculations of the smaller system indicate that the first reaction step, the formation of the intermediate, is rate-limiting, the calculations including the protein environment show that the decomposition of the intermediate is probably rate-limiting. The results clearly show that the protein environment cannot be disregarded during quantum-mechanical calculations of enzyme mechanisms.



How to cite
APA: Schürer, G., Lanig, H., & Clark, T. (2000). The mode of action of phospholipase A(2): Semiempirical MO calculations including the protein environment. Journal of Physical Chemistry B, 104(6), 1349-1361. https://dx.doi.org/10.1021/jp993330i

MLA: Schürer, Gudrun, Harald Lanig, and Timothy Clark. "The mode of action of phospholipase A(2): Semiempirical MO calculations including the protein environment." Journal of Physical Chemistry B 104.6 (2000): 1349-1361.

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