Active Site Hydrophobicity and the Convergent Evolution of Paraoxonase Activity in Structurally Divergent Enzymes: The Case of Serum Paraoxonase 1.
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Blaha-Nelson D, Krüger DM, Szeler K, Ben-David M, Kamerlin SC
J. Am. Chem. Soc. 139 (3) 1155-1167 [2017-01-25; online 2017-01-11]
Serum paraoxonase 1 (PON1) is a native lactonase capable of promiscuously hydrolyzing a broad range of substrates, including organophosphates, esters, and carbonates. Structurally, PON1 is a six-bladed β-propeller with a flexible loop (residues 70-81) covering the active site. This loop contains a functionally critical Tyr at position 71. We have performed detailed experimental and computational analyses of the role of selected Y71 variants in the active site stability and catalytic activity in order to probe the role of Y71 in PON1's lactonase and organophosphatase activities. We demonstrate that the impact of Y71 substitutions on PON1's lactonase activity is minimal, whereas the k
PubMed 28026940
DOI 10.1021/jacs.6b10801
Crossref 10.1021/jacs.6b10801