Change search
ReferencesLink to record
Permanent link

Direct link
Phosphate Hydrolysis by the Fe-2-Ca-3-Dependent Alkaline Phosphatase PhoX: Mechanistic Insights from DFT calculations
Stockholm University, Faculty of Science, Department of Organic Chemistry.
Number of Authors: 2
2015 (English)In: Inorganic Chemistry, ISSN 0020-1669, E-ISSN 1520-510X, Vol. 54, no 24, 11941-11947 p.Article in journal (Refereed) Published
Abstract [en]

PhoX is a pentanudear metalloenzyme that employs two ferric ions and three calcium ions to catalyze the hydrolysis of phosphomonoesters. On the basis of the X-ray structure of PhoX (Science 2014, 34S, 1170-1173), a model of the active site is designed, and quantum chemical calculations are used to investigate the reaction mechanism of this enzyme. The calculations support the experimental suggestion, in which the two high spin ferric ions interact in an antiferromagnetic fashion. The two step mechanism proposed by experimentalists has been investigated. The nudeophilic attack of a trinudear bridging oxo group on the phosphorus center was calculated to be the first step, which is concomitant with the departure of the phenolate, which is stabilized by a calcium ion. The second step is a reverse attack by a water molecule activated by a calciumbound hydroxide, leading to the regeneration of the bridging oxo group. The second step was calculated to have a barrier of 27.6 kcal/mol. The high barrier suggests that the alternative mechanism involving phosphate release directly from the active site seems to be more likely. All five metal ions are involved in the catalysis by stabilizing the pentacoordinated trigonal bipyramidal transition states.

Place, publisher, year, edition, pages
2015. Vol. 54, no 24, 11941-11947 p.
National Category
Organic Chemistry
Identifiers
URN: urn:nbn:se:su:diva-125897DOI: 10.1021/acs.inorgchem.5b02268ISI: 000367118100040PubMedID: 26651528OAI: oai:DiVA.org:su-125897DiVA: diva2:896001
Available from: 2016-01-20 Created: 2016-01-19 Last updated: 2016-01-20Bibliographically approved

Open Access in DiVA

No full text

Other links

Publisher's full textPubMed

Search in DiVA

By author/editor
Siegbahn, Per E. M.
By organisation
Department of Organic Chemistry
In the same journal
Inorganic Chemistry
Organic Chemistry

Search outside of DiVA

GoogleGoogle Scholar
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: 7 hits
ReferencesLink to record
Permanent link

Direct link