A1 Refereed original research article in a scientific journal
The structural basis for pyrophosphatase catalysis
Authors: Heikinheimo P, Lehtonen J, Baykov A, Lahti R, Cooperman BS, Goldman A
Publisher: CURRENT BIOLOGY LTD
Publication year: 1996
Journal: Structure
Journal name in source: STRUCTURE
Journal acronym: STRUCTURE
Volume: 4
Issue: 12
First page : 1491
Last page: 1508
Number of pages: 18
ISSN: 0969-2126
DOI: https://doi.org/10.1016/S0969-2126(96)00155-4(external)
Abstract
Conclusions: Our structure-based model of the PPase mechanism posits that the nucleophile is the hydroxide ion mentioned above. This aspect of the mechanism is formally analogous to the 'two-metal ion' mechanism of alkaline phosphatase, exonucleases and polymerases. A third metal ion coordinates another water molecule that is probably the required general acid. Extensive Lewis acid coordination and hydrogen bonds provide charge shielding of the electrophile and lower the pK(a) of the leaving group. This 'three-metal ion' mechanism is in detail different from that of other phosphoryl transfer enzymes, presumably reflecting how ancient the reaction is.
Conclusions: Our structure-based model of the PPase mechanism posits that the nucleophile is the hydroxide ion mentioned above. This aspect of the mechanism is formally analogous to the 'two-metal ion' mechanism of alkaline phosphatase, exonucleases and polymerases. A third metal ion coordinates another water molecule that is probably the required general acid. Extensive Lewis acid coordination and hydrogen bonds provide charge shielding of the electrophile and lower the pK(a) of the leaving group. This 'three-metal ion' mechanism is in detail different from that of other phosphoryl transfer enzymes, presumably reflecting how ancient the reaction is.