An efficient, multiply promiscuous hydrolase in the alkaline phosphatase superfamily

Bert Van Loo, Stefanie Jonas, Ann C. Babtie, Alhosna Benjdia, Olivier Berteau, Marko Hyvönen, Florian Hollfelder*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

69 Citations (Scopus)

Abstract

We report a catalytically promiscuous enzyme able to efficiently promote the hydrolysis of six different substrate classes. Originally assigned as a phosphonate monoester hydrolase (PMH) this enzyme exhibits substantial second-order rate accelerations ((kcat/KM) /k w), ranging from 107 to as high as 1019, for the hydrolyses of phosphate mono-, di-, and triesters, phosphonate monoesters, sulfate monoesters, and sulfonate monoesters. This substrate collection encompasses a range of substrate charges between 0 and -2, transition states of a different nature, and involves attack at two different reaction centers (P and S). Intrinsic reactivities (half-lives) range from 200 days to 105 years under near neutrality. The substantial rate accelerations for a set of relatively difficult reactions suggest that efficient catalysis is not necessarily limited to efficient stabilization of just one transition state. The crystal structure of PMH identifies it as a member of the alkaline phosphatase superfamily. PMH encompasses four of the native activities previously observed in this superfamily and extends its repertoire by two further activities, one of which, sulfonate monoesterase, has not been observed previously for a natural enzyme. PMH is thus one of the most promiscuous hydrolases described to date. The functional links between superfamily activities can be presumed to have played a role in functional evolution by gene duplication.

Original languageEnglish
Pages (from-to)2740-2745
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume107
Issue number7
Early online date27 Jan 2010
DOIs
Publication statusPublished - 16 Feb 2010
Externally publishedYes

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