NPP-type ectophosphodiesterases: unity in diversity

Stefan, Cristiana; Jansen, Silvia; Bollen, Mathieu

doi:10.1016/j.tibs.2005.08.005

Cited by 338 publications

(341 citation statements)

References 70 publications

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“…All mutations are reported in ref. [307] NPP1 has been linked to insulin resistance and type 2 diabetes (for review, see [334][335][336]). NPP3 has been shown to promote differentiation and invasion of glial cells but the underlying mechanisms have not been identified [337].…”

Section: General Properties and Functional Rolementioning

confidence: 99%

“…But it can also be hydrolyzed into ADP and P i . It has been suggested that hydrolysis of ATP into AMP involves a covalent AMP intermediate whereas hydrolysis into ADP involves a phosphate-bound intermediate, depending on how the substrate approaches the catalytic site [312,334]. The previously described autophosphorylation of NPP1 [366,367] would then represent one of its covalent intermediates for ATP hydrolysis.…”

Section: General Properties and Functional Rolementioning

confidence: 99%

“…In contrast, NPP4-7 consist of solely the catalytic domain. The catalytic domains of NPP1-7 share 24 to 60 % amino acid identity between the human isoforms [334,367]. The nuclease-like domain itself reveals no catalytic activity, but it bears isoform-specific determinants for catalysis.…”

Section: General Molecular Propertiesmentioning

confidence: 99%

“…NPP1-NPP3 further contain two cysteine-rich tandem repeats, the somatomedin B-like domains proximal to their N-terminal TMD. It is thought that these domains function as protein interaction domains, similar to the somatomedin B domain of vitronectin, a large glycoprotein found in blood and the extracellular matrix [334].…”

Section: General Molecular Propertiesmentioning

confidence: 99%

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Cellular function and molecular structure of ecto-nucleotidases

Zimmermann

Zebisch

Sträter

2012

Purinergic Signalling

888

922

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Ecto-nucleotidases play a pivotal role in purinergic signal transmission. They hydrolyze extracellular nucleotides and thus can control their availability at purinergic P2 receptors. They generate extracellular nucleosides for cellular reuptake and salvage via nucleoside transporters of the plasma membrane. The extracellular adenosine formed acts as an agonist of purinergic P1 receptors. They also can produce and hydrolyze extracellular inorganic pyrophosphate that is of major relevance in the control of bone mineralization. This review discusses and compares four major groups of ectonucleotidases: the ecto-nucleoside triphosphate diphosphohydrolases, ecto-5′-nucleotidase, ecto-nucleotide pyrophosphatase/phosphodiesterases, and alkaline phosphatases. Only recently and based on crystal structures, detailed information regarding the spatial structures and catalytic mechanisms has become available for members of these four ecto-nucleotidase families. This permits detailed predictions of their catalytic mechanisms and a comparison between the individual enzyme groups. The review focuses on the principal biochemical, cell biological, catalytic, and structural properties of the enzymes and provides brief reference to tissue distribution, and physiological and pathophysiological functions.

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Section: General Properties and Functional Rolementioning

confidence: 99%

Section: General Properties and Functional Rolementioning

confidence: 99%

Section: General Molecular Propertiesmentioning

confidence: 99%

Section: General Molecular Propertiesmentioning

confidence: 99%

See 2 more Smart Citations

Cellular function and molecular structure of ecto-nucleotidases

Zimmermann

Zebisch

Sträter

2012

Purinergic Signalling

888

922

View full text Add to dashboard Cite

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“…expressed on osteoblasts, chondrocytes, and vascular smooth muscle cells (9) and hydrolyzes extracellular nucleotide triphosphates to liberate inorganic pyrophosphate (PPi), a potent inhibitor of mineralization. (10,11) Hence, ENPP1 deficiency in GACI1 reduces extracellular PPi levels and predisposes to ectopic calcification (EC).…”

mentioning

confidence: 99%

Severe skeletal toxicity from protracted etidronate therapy for generalized arterial calcification of infancy

Otero

Gottesman

McAlister

et al. 2012

Journal of Bone and Mineral Research

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Generalized arterial calcification (AC) of infancy (GACI) is an autosomal recessive disorder that features hydroxyapatite deposition within arterial elastic fibers. Untreated, approximately 85% of GACI patients die by 6 months of age from cardiac ischemia and congestive heart failure. The first-generation bisphosphonate etidronate (EHDP; ethane-1-hydroxy-1,1-diphosphonic acid, also known as 1-hydroxyethylidene-bisphosphonate) inhibits bone resorption and can mimic endogenous inorganic pyrophosphate by blocking mineralization. With EHDP therapy for GACI, AC may resolve without recurrence upon treatment cessation. Skeletal disease is not an early characteristic of GACI, but rickets can appear from acquired hypophosphatemia or prolonged EHDP therapy. We report a 7-year-old boy with GACI referred for profound, acquired, skeletal disease. AC was gone after 5 months of EHDP therapy during infancy, but GACI-related joint calcifications progressed. He was receiving EHDP, 200 mg/day orally, and had odynodysphagia, diffuse opioid-controlled pain, plagiocephaly, facial dysmorphism, joint calcifications, contractures, and was wheelchair bound. Biochemical parameters of mineral homeostasis were essentially normal. Serum osteocalcin was low and the brain isoform of creatine kinase and tartrate-resistant acid phosphatase 5b (TRAP-5b) were elevated as in osteopetrosis. Skeletal radiographic findings resembled pediatric hypophosphatasia with pancranial synostosis, long-bone bowing, widened physes, as well as metaphyseal osteosclerosis, cupping and fraying, and ''tongues'' of radiolucency. Radiographic features of osteopetrosis included osteosclerosis and femoral Erlenmeyer flask deformity. After stopping EHDP, he improved rapidly, including remarkable skeletal healing and decreased joint calcifications. Profound, but rapidly reversible, inhibition of skeletal mineralization with paradoxical calcifications near joints can occur in GACI from protracted EHDP therapy. Although EHDP treatment is lifesaving in GACI, surveillance for toxicity is crucial. ß

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