Schürer G, Lanig H, Clark T, Lanig H (2000)
Publication Status: Published
Publication Type: Journal article
Publication year: 2000
Publisher: American Chemical Society
Book Volume: 104
Pages Range: 1349-1361
Journal Issue: 6
DOI: 10.1021/jp993330i
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.
APA:
Schürer, G., Lanig, H., Clark, T., & Lanig, H. (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://doi.org/10.1021/jp993330i
MLA:
Schürer, Gudrun, et al. "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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