Cofactors

Ca(2+).

Reaction Mechanism

phospholipase A1 By Reference

The outer membrane phospholipase A (OMPLA) is an integral membrane enzyme present in the outer membrane of Gram-negative bacteria. It catalyses the hydrolysis of acylester bonds in phospholipids. The physiological function of OMPLA is still not known.




• Summary
• Step 1
• Step 2
• Step 3
• Step 4
• Products

The mechanism of OMPLA is analogous to that of serine hydrolases. His162 acts as a base to deprotonate the side chain of Ser164 to allow its nucleophilic attack on the ester bond. The tetrahedral transition state is stabilised by an oxyanion hole formed by the amide of Gly166 and 2 water molecules. His162 protonates the leaving group and then deprotonates a water molecule to allow its nucleophilic attack on the acylenzyme intermediate. The essential Ca2+ ion increases the nucleophilicity of the serine and polarises the ester carbonyl bond to facilitate the nucleophilic attack. It is also involved in the oxyanion stabilisation.

Catalytic Residues

AA	Uniprot	Uniprot Resid	PDB	PDB Resid
Ser	P0A921	164	1qd6	115
His	P0A921	162	1qd6	113
Ser	P0A921	172	1qd6	123
Asn	P0A921	176	1qd6	127
Gly	P0A921	166	1qd6	117
Ser	P0A921	126	1qd6	77
Arg	P0A921	167	1qd6	118

Step Components

overall reactant used, proton transfer, overall product formed, unimolecular elimination by the conjugate base, bimolecular nucleophilic addition, intermediate formation, intermediate terminated, native state of enzyme regenerated



Step 1.

His162 acts as a general base activating the Ser164 hydroxyl group for nucleophilic attack on the carbonyl carbon of the ester bond. The third component of this catalytic triad- Asn176 acts to increase the basicity of the histidine. The oxyanion intermediate formed is stabilized by the amide group of Gly166, the calcium ion and the water molecules coordinated to the calcium.



Step 2.

The tetrahedral intermediate collapses and 2-acyl-sn-glycero-3-phosphocholine is eliminated.



Step 3.

His162 activates water for nucleophilic attack and another oxyanion intermediate is formed.



Step 4.

The tetrahedral intermediate collapses and Ser164 is eliminated.



Products.

The products of the reaction.

View Reaction Mechanisms in M-CSA

Reaction Parameters

There are no kinetic parameters information for this Enzyme

Associated Proteins

Citations

• The cell functions of phospholipase C-1, Ca²⁺/H⁺ exchanger-1, and secretory phospholipase A₂ in tolerance to stress conditions and cellulose degradation in Neurospora crassa.
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• Phospholipase D1 activity is crucial for cytosolic phospholipase A₂ -dependent prostaglandin E₂ formation in murine osteoblastic MC3T3-E1 cells.
• Risk factors for acute ischemic stroke in patients with type 2 diabetes mellitus
• Safety evaluation of the food enzyme phospholipase A2 from the genetically modified Aspergillus niger strain PLA
• The latest model has just arrived! A new experimental mouse model of PLA2R1-associated membranous nephropathy.
• Synthesis and Structural Characterization of Novel Dimers of Dipyridothiazine as Promising Antiproliferative Agents.
• Si Shen Wan Regulates Phospholipase Cγ-1 and PI3K/Akt Signal in Colonic Mucosa from Rats with Colitis.