Publication Date:
2014-09-06
Description:
Alkaline phosphatases play a crucial role in phosphate acquisition by microorganisms. To expand our understanding of catalysis by this class of enzymes, we have determined the structure of the widely occurring microbial alkaline phosphatase PhoX. The enzyme contains a complex active-site cofactor comprising two antiferromagnetically coupled ferric iron ions (Fe(3+)), three calcium ions (Ca(2+)), and an oxo group bridging three of the metal ions. Notably, the main part of the cofactor resembles synthetic oxide-centered triangular metal complexes. Structures of PhoX-ligand complexes reveal how the active-site metal ions bind substrate and implicate the cofactor oxo group in the catalytic mechanism. The presence of iron in PhoX raises the possibility that iron bioavailability limits microbial phosphate acquisition.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4175392/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉 〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4175392/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Yong, Shee Chien -- Roversi, Pietro -- Lillington, James -- Rodriguez, Fernanda -- Krehenbrink, Martin -- Zeldin, Oliver B -- Garman, Elspeth F -- Lea, Susan M -- Berks, Ben C -- BB/F02150X/1/Biotechnology and Biological Sciences Research Council/United Kingdom -- F02150X/Biotechnology and Biological Sciences Research Council/United Kingdom -- New York, N.Y. -- Science. 2014 Sep 5;345(6201):1170-3. doi: 10.1126/science.1254237.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biochemistry, University of Oxford, South Parks Road, Oxford OX1 3QU, UK. ; Sir William Dunn School of Pathology, University of Oxford, South Parks Road, Oxford OX1 3RE, UK. ; Sir William Dunn School of Pathology, University of Oxford, South Parks Road, Oxford OX1 3RE, UK. ben.berks@bioch.ox.ac.uk susan.lea@path.ox.ac.uk. ; Department of Biochemistry, University of Oxford, South Parks Road, Oxford OX1 3QU, UK. ben.berks@bioch.ox.ac.uk susan.lea@path.ox.ac.uk.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25190793" target="_blank"〉PubMed〈/a〉
Keywords:
Alkaline Phosphatase/*chemistry/genetics
;
Bacterial Proteins/*chemistry/genetics
;
Calcium/*chemistry
;
Catalysis
;
Catalytic Domain
;
Coenzymes/*chemistry
;
Iron/*chemistry
;
Ligands
;
Phosphates/*metabolism
;
Protein Structure, Secondary
;
Pseudomonas fluorescens/enzymology
;
Recombinant Proteins/chemistry/genetics
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
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