Membrane Allostery and Unique Hydrophobic Sites Promote Enzyme Substrate Specificity.

ABSTRACT: We demonstrate that lipidomics coupled with molecular dynamics reveal unique phospholipase A2 specificity toward membrane phospholipid substrates. We discovered unexpected headgroup and acyl-chain specificity for three major human phospholipases A2. The differences between each enzyme's specificity, coupled with molecular dynamics-based structural and binding studies, revealed unique binding sites and interfacial surface binding moieties for each enzyme that explain the observed specificity at a hitherto inaccessible structural level. Surprisingly, we discovered that a unique hydrophobic binding site for the cleaved fatty acid dominates each enzyme's specificity rather than its catalytic residues and polar headgroup binding site. Molecular dynamics simulations revealed the optimal phosphol

SUBMITTER: Mouchlis VD 

PROVIDER: S-EPMC5846079 | biostudies-literature | 2018 Mar

REPOSITORIES: biostudies-literature