Skip to content

Research at St Andrews

Comparative modelling of human PHOSPHO1 reveals a new group of phosphatases within the haloacid dehalogenase superfamily

Research output: Contribution to journalArticle

DOI

Author(s)

Alan James Stewart, R Schmid, CA Blindauer, SJ Paisey, C Farquharson

School/Research organisations

Abstract

PHOSPHO1 is a recently identified phosphatase whose expression is upregulated in mineralizing cells and is implicated in the generation of inorganic phosphate for matrix mineralization, a process central to skeletal development. The enzyme is a member of the haloacid dehalogenase (HAD) superfamily of magnesium-dependent hydrolases. However, the natural substrate(s) is as yet unidentified and to date no structural information is known. We have identified homologous proteins in a number of species and have modelled human PHOSPHO1 based upon the crystal structure of phosphoserine phosphatase (PSP) from Methanococcus jannaschii. The model includes the catalytic Mg2+ atom bound via three conserved Asp residues (Asp32, Asp34 and Asp203); O-ligands are also provided by a phosphate anion and two water molecules. Additional residues involved in PSP-catalysed hydrolysis are conserved and are located nearby, suggesting both enzymes share a similar reaction mechanism. In PHOSPHO1, none of the PSP residues that confer the enzyme’s substrate specificity (Arg56, Glu20, Met43 and Phe49) are conserved. Instead, we propose that two fully conserved Asp residues (Asp43 and Asp123), not present in PSPs contribute to substrate specificity in PHOSPHO1. Our findings show that PHOSPHO1 is not a member of the subfamily of PSPs but belongs to a novel, closely related enzyme group within the HAD superfamily.
Close

Details

Original languageEnglish
Pages (from-to)889-895
Number of pages7
JournalProtein Engineering
Volume16
Issue number12
DOIs
Publication statusPublished - Dec 2003

    Research areas

  • Haloacid dehalogenase superfamily, Homology modelling, Matrix mineralization, Phosphatase, PHOSPHO1

Discover related content
Find related publications, people, projects and more using interactive charts.

View graph of relations

Related by author

  1. Reduced plasma magnesium levels in type-1 diabetes associate with prothrombotic changes in fibrin clotting and fibrinolysis

    Sobczak, A. I. S., Phoenix, F. A., Pitt, S. J., Ajjan, R. A. & Stewart, A. J., 3 Jan 2020, In : Thrombosis and Haemostasis. eFirst, 10 p.

    Research output: Contribution to journalArticle

  2. Coagulatory defects in type-1 and type-2 diabetes

    Sobczak, A. I. S. & Stewart, A. J., 16 Dec 2019, In : International Journal of Molecular Sciences. 20, 24, 28 p., 6345.

    Research output: Contribution to journalReview article

  3. The X files: ''The mystery of X chromosome instability in Alzheimer's disease''

    Bajic, V. P., Essak, M., Zivkovic, L., Stewart, A. J., Zafirovic, S., Bajic, V., Gojobori, T., Isenovic, E. & Spremo-Potparevic, B., 13 Dec 2019, (Accepted/In press) In : Frontiers in Genetics.

    Research output: Contribution to journalReview article

  4. A metalloproteomic analysis of interactions between plasma proteins and zinc: elevated fatty acid levels affect zinc distribution

    Coverdale, J. P. C., Barnett, J. P., Adamu, A. H., Griffiths, E. J., Stewart, A. J. & Blindauer, C. A., 1 Nov 2019, In : Metallomics. 11, 11, p. 1805-1819 15 p.

    Research output: Contribution to journalArticle

  5. Plasma non-esterified fatty acids contribute to increased coagulability in type-2 diabetes through altered plasma zinc speciation

    Sobczak, A. I. S., Katundu, K. G. H., Phoenix, F. A., Khazaipoul, S., Yu, R., Lampiao, F., Stefanowicz, F., Blindauer, C. A., Pitt, S. J., Smith, T. K., Ajjan, R. A. & Stewart, A. J., 28 Aug 2019, In : biorxiv. 38 p.

    Research output: Contribution to journalArticle

Related by journal

  1. Enzyme thermostability and thermoactivity

    Danson, M. J., Hough, D. W., Russell, R. J. M., Taylor, G. L. & Pearl, L., Aug 1996, In : Protein Engineering. 9, 8, p. 629-630 2 p.

    Research output: Contribution to journalArticle

ID: 433864

Top