4brk Citations

Crystallographic Snapshots along the Reaction Pathway of Nucleoside Triphosphate Diphosphohydrolases.

Structure (2013)
Related entries: 4brg, 4br9, 4br4, 4br5, 4br7, 4br0, 4brq, 4br2, 4brl, 4brm, 4brn, 4bro, 4brh, 4bri, 4brp, 4brd, 4bre, 4brf, 4brc, 4bra, 4bqz

Cited: 10 times
EuropePMC logo PMID: 23830739


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°.

Reviews citing this publication (2)

Articles citing this publication (8)

  1. Hen egg-white lysozyme crystallisation: protein stacking and structure stability enhanced by a Tellurium(VI)-centred polyoxotungstate. Bijelic A, Molitor C, Mauracher SG, Al-Oweini R, Kortz U, Rompel A. Chembiochem 16 233-241 (2015)
  2. Multiple ecto-nucleoside triphosphate diphosphohydrolases facilitate intracellular replication of Legionella pneumophila. Riedmaier P, Sansom FM, Sofian T, Beddoe T, Schuelein R, Newton HJ, Hartland EL. Biochem. J. 462 279-289 (2014)
  3. The ATP/ADP substrate specificity switch between Toxoplasma gondii NTPDase1 and NTPDase3 is caused by an altered mode of binding of the substrate base. Krug U, Totzauer R, Zebisch M, Sträter N. Chembiochem 14 2292-2300 (2013)
  4. Crystal structure of NTPDase2 in complex with the sulfoanthraquinone inhibitor PSB-071. Zebisch M, Baqi Y, Schäfer P, Müller CE, Sträter N. J. Struct. Biol. 185 336-341 (2014)
  5. Structures of Legionella pneumophila NTPDase1 in complex with polyoxometallates. Zebisch M, Krauss M, Schäfer P, Sträter N. Acta Crystallogr. D Biol. Crystallogr. 70 1147-1154 (2014)
  6. Alterations of ectonucleotidases and acetylcholinesterase activities in lymphocytes of Down syndrome subjects: relation with inflammatory parameters. Rodrigues R, Debom G, Soares F, Machado C, Pureza J, Peres W, de Lima Garcias G, Duarte MF, Schetinger MR, Stefanello F, Braganhol E, Spanevello R. Clin. Chim. Acta 433 105-110 (2014)
  7. The biochemical properties of the Arabidopsis ecto-nucleoside triphosphate diphosphohydrolase AtAPY1 contradict a direct role in purinergic signaling. Massalski C, Bloch J, Zebisch M, Steinebrunner I. PLoS ONE 10 e0115832 (2015)
  8. Structural and functional characterization of a cold adapted TPM-domain with ATPase/ADPase activity. Cerutti ML, Otero LH, Smal C, Pellizza L, Goldbaum FA, Klinke S, Aran M. J. Struct. Biol. 197 201-209 (2017)