RGD Reference Report - Crystallographic evidence for a domain motion in rat nucleoside triphosphate diphosphohydrolase (NTPDase) 1. - Rat Genome Database

RGD Reference Report - Crystallographic evidence for a domain motion in rat nucleoside triphosphate diphosphohydrolase (NTPDase) 1. - Rat Genome Database

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Crystallographic evidence for a domain motion in rat nucleoside triphosphate diphosphohydrolase (NTPDase) 1.
Authors:	Zebisch, Matthias Krauss, Michel Schäfer, Petra Sträter, Norbert
Citation:	Zebisch M, etal., J Mol Biol. 2012 Jan 13;415(2):288-306. doi: 10.1016/j.jmb.2011.10.050. Epub 2011 Nov 12.
RGD ID:	401901231
Pubmed:	PMID:22100451 (View Abstract at PubMed)
DOI:	DOI:10.1016/j.jmb.2011.10.050 (Journal Full-text)
Nucleoside triphosphate diphosphohydrolases (NTPDases) are a physiologically important class of membrane-bound ectonucleotidases responsible for the regulation of extracellular levels of nucleotides. CD39 or NTPDase1 is the dominant NTPDase of the vasculature. By hydrolyzing proinflammatory ATP and platelet-activating ADP to AMP, it blocks platelet aggregation and supports blood flow. Thus, great interest exists in understanding the structure and dynamics of this prototype member of the eukaryotic NTPDase family. Here, we report the crystal structure of a variant of soluble NTPDase1 lacking a putative membrane interaction loop identified between the two lobes of the catalytic domain. ATPase and ADPase activities of this variant are determined via a newly established kinetic isothermal titration calorimetry assay and compared to that of the soluble NTPDase1 variant characterized previously. Complex structures with decavanadate and heptamolybdate show that both polyoxometallates bind electrostatically to a loop that is involved in binding of the nucleobase. In addition, a comparison of the domain orientations of the four independent proteins in the crystal asymmetric unit provides the first direct experimental evidence for a domain motion of NTPDases. An interdomain rotation angle of up to 7.4° affects the active site cleft between the two lobes of the protein. Comparison with a previously solved bacterial NTPDase structure indicates that the domains may undergo relative rotational movements of more than 20°. Our data support the idea that the influence of transmembrane helix dynamics on activity is achieved by coupling to a domain motion.

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Object Symbol	Species	Term	Qualifier	Evidence	With	Notes	Source	Original Reference(s)
Entpd1	Rat	nucleoside diphosphate phosphatase activity	enables	IDA		PMID:22100451	UniProt
Entpd1	Rat	ribonucleoside triphosphate phosphatase activity	enables	IDA		PMID:22100451	UniProt

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Genes (Rattus norvegicus)

Entpd1 (ectonucleoside triphosphate diphosphohydrolase 1)

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