title: Favored reaction mechanism of calcium-dependent phospholipase A(2). Insights from density functional exploration.
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.
authors: Dipartimento 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.
authors: Monica
authors: M
authors: Leopoldini
authors: Nino
authors: N
authors: Russo
authors: Marirosa
authors: M
authors: Toscano
mesh_terms: D055162:Biocatalysis; D002118:Calcium / Q000737:chemistry*; D020134:Catalytic Domain; D006860:Hydrogen Bonding; D006868:Hydrolysis; D010741:Phospholipases A / Q000737:chemistry / Q000378:metabolism*; D010743:Phospholipids / Q000378:metabolism; D011789:Quantum Theory; D012997:Solvents / Q000737:chemistry; D013816:Thermodynamics
chemical_list: D010743:Phospholipids; D012997:Solvents; D010741:Phospholipases A; D002118:Calcium