Format

Send to

Choose Destination
Structure. 2013 Aug 6;21(8):1460-75. doi: 10.1016/j.str.2013.05.016. Epub 2013 Jul 3.

Crystallographic snapshots along the reaction pathway of nucleoside triphosphate diphosphohydrolases.

Author information

1
Institute of Bioanalytical Chemistry, Center for Biotechnology and Biomedicine, Faculty of Chemistry and Mineralogy, University of Leipzig, 04103 Leipzig, Germany.

Abstract

In vertebrates, membrane-bound ecto-nucleoside triphosphate diphosphohydrolases (NTPDases) on the cell surface are responsible for signal conversion and termination in purinergic signaling by extracellular nucleotides. Here we present apo and complex structures of the rat NTPDase2 extracellular domain and Legionella pneumophila NTPDase1, including a high-resolution structure with a transition-state analog. Comparison of ATP and ADP binding modes shows how NTPDases engage the same catalytic site for hydrolysis of nucleoside triphosphates and diphosphates. We find that this dual specificity is achieved at the expense of base specificity. Structural and mutational studies indicate that a conserved active-site water is replaced by the phosphate product immediately after phosphoryl transfer. Partial base specificity for purines in LpNTPDase1 is based on a different intersubunit base binding site for pyrimidine bases. A comparison of the bacterial enzyme in six independent crystal forms shows that NTPDases can undergo a domain closure motion of at least 17°.

PMID:
23830739
DOI:
10.1016/j.str.2013.05.016
[Indexed for MEDLINE]
Free full text

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center