Favored reaction mechanism of calcium-dependent phospholipase A(2). Insights from density functional exploration
Monica Leopoldini1, Nino Russo, Marirosa Toscano
1Dipartimento di Chimica and Centro di Calcolo ad Alte Prestazioni per Elaborazioni Parallele e Distribuite-Centro d'Eccellenza MIUR, Università della Calabria, I-87030 Arcavacata di Rende (CS), Italy.
Abstract:
The sn-2 acyl hydrolysis of phospholipids catalyzed by phospholipase A(2) (PLA(2)) was investigated at the density functional B3LYP level. The PLA(2) active site is represented by quantum-chemical models that are based on available X-ray crystal structures. The two still controversial catalytic triad and calcium-coordinated oxyanion reaction mechanisms were considered. Tetrahedral intermediate formation in the first mechanism and the cleavage of the C-O bond in the second one are the rate-determining steps. Both mechanisms, in the gas phase and in the protein-like environment, yielded potential energy profiles with low energy barriers and consequently the comparison did not indicate a clear preference for one or the other path. An alternative mechanism, based on some corrections to the previously suggested ones, provides for an optional pathway for the enzyme activity.
More Related Videos
07:11Dissipative Microgravimetry to Study the Binding Dynamics of the Phospholipid Binding Protein Annexin A2 to Solid-supported Lipid Bilayers Using a Quartz Resonator
Published on: November 1, 2018
08:59Defining Substrate Specificities for Lipase and Phospholipase Candidates
Published on: November 23, 2016
Related Concept Videos
IP3/DAG Signaling Pathway
Calmodulin-dependent Signaling
The Ca2+-CaM complex does not have enzymatic activity by itself. Instead, the complex binds downstream target proteins, including membrane proteins or enzymes,...
Asymmetric Lipid Bilayer
Phosphoinositides and PIPs
Different phosphoinositides are synthesized and recruited on the cytosolic face of the plasma membrane. The localization of specific phosphoinositides concentrated in separate membrane...
Protein Kinases and Phosphatases
Protein kinases
Many proteins in the cell are regulated by phosphorylation, the addition of a phosphate group. A family of enzymes called kinases...
Synthesis of Phosphatidylcholine in the ER Membrane
The major components of all eukaryotic cell...
