Change search
ReferencesLink to record
Permanent link

Direct link
Examining the promiscuous phosphatase activity of Pseudomonas aeruginosa arylsulfatase: A comparison to analogous phosphatases
Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology. Biophysical Structural Chemistry, University of Leiden.
University of Cambridge, Department of Biochemistry.
Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, Computational and Systems Biology. (Kamerlin)
2012 (English)In: Proteins: Structure, Function and Bioinformatics, ISSN 1097-0134, Vol. 80, no 4, 1211-1226 p.Article in journal (Refereed) Published
Abstract [en]

Pseudomonas aeruginosa arylsulfatase (PAS) is a bacterial sulfatase capable ofhydrolyzing a range of sulfate esters. Recently, it has been demonstrated to also show very high proficiency for phosphate ester hydrolysis. Such proficient catalytic promiscuity is significant, as promiscuity has been suggested to play an important role in enzyme evolution. Additionally, a comparative study of the hydrolyses of the p-nitrophenyl phosphate and sulfate monoesters in aqueous solution has demonstrated that despite superficial similarities, the two reactions proceed through markedly different transition states with very different solvation effects, indicating that the requirements for the efficient catalysis of the two reactions by an enzyme will also be very different (and yet they are both catalyzed by thesame active site). This work explores the promiscuous phosphomonoesterase activity ofPAS. Specifically, we have investigated the identity of the most likely base for the initial activation of the unusual formylglycine hydrate nucleophile (which is common to many sulfatases), and demonstrate that a concerted substrate-as-base mechanism is fully consistent with the experimentally observed data. This is very similar to other related systems, and suggests that, as far as the phosphomonoesterase activity of PAS is concerned, the sulfatase behaves like a classical phosphatase, despite the fact that such a mechanism is unlikely to be available to the native substrate (based on pKa considerations and studies of model systems). Understanding such catalytic versatility can be used to design novel artificial enzymes that are far more proficient than the current generation ofdesigner enzymes. 

Place, publisher, year, edition, pages
2012. Vol. 80, no 4, 1211-1226 p.
National Category
Theoretical Chemistry
Research subject
Biochemistry; Chemistry with specialization in Biophysics
URN: urn:nbn:se:uu:diva-190391DOI: 10.1002/prot.24020ISI: 000300984700019OAI: diva2:583357
Swedish Research Council, 2012-5026Swedish National Infrastructure for Computing (SNIC), 002/12-26
Available from: 2013-01-07 Created: 2013-01-07 Last updated: 2016-04-08Bibliographically approved

Open Access in DiVA

fulltext(1634 kB)89 downloads
File information
File name FULLTEXT02.pdfFile size 1634 kBChecksum SHA-512
Type fulltextMimetype application/pdf

Other links

Publisher's full text

Search in DiVA

By author/editor
Kamerlin, Lynn
By organisation
Department of Cell and Molecular BiologyComputational and Systems Biology
Theoretical Chemistry

Search outside of DiVA

GoogleGoogle Scholar
Total: 89 downloads
The number of downloads is the sum of all downloads of full texts. It may include eg previous versions that are now no longer available

Altmetric score

Total: 149 hits
ReferencesLink to record
Permanent link

Direct link