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4B56

Structure of ectonucleotide pyrophosphatase-phosphodiesterase-1 (NPP1)

Summary for 4B56
Entry DOI10.2210/pdb4b56/pdb
DescriptorECTONUCLEOTIDE PYROPHOSPHATASE/PHOSPHODIESTERASE FAMILY MEMBER 1, alpha-D-mannopyranose-(1-3)-[alpha-D-mannopyranose-(1-6)]beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, ... (8 entities in total)
Functional Keywordshydrolase
Biological sourceMUS MUSCULUS (MOUSE)
Total number of polymer chains2
Total formula weight192777.26
Authors
Jansen, S.,Perrakis, A.,Ulens, C.,Winkler, C.,Andries, M.,Joosten, R.P.,Van Acker, M.,Luyten, F.P.,Moolenaar, W.H.,Bollen, M. (deposition date: 2012-08-02, release date: 2012-09-19, Last modification date: 2024-11-20)
Primary citationJansen, S.,Perrakis, A.,Ulens, C.,Winkler, C.,Andries, M.,Joosten, R.P.,Van Acker, M.,Luyten, F.P.,Moolenaar, W.H.,Bollen, M.
Structure of Npp1, an Ectonucleotide Pyrophosphatase/Phosphodiesterase Involved in Tissue Calcification.
Structure, 20:1948-, 2012
Cited by
PubMed Abstract: Ectonucleotide pyrophosphatase/phosphodiesterase-1 (NPP1) converts extracellular nucleotides into inorganic pyrophosphate, whereas its close relative NPP2/autotaxin hydrolyzes lysophospholipids. NPP1 regulates calcification in mineralization-competent tissues, and a lack of NPP1 function underlies calcification disorders. Here, we show that NPP1 forms homodimers via intramembrane disulfide bonding, but is also processed intracellularly to a secreted monomer. The structure of secreted NPP1 reveals a characteristic bimetallic active site and a nucleotide-binding groove, but it lacks the lipid-binding pocket and open tunnel present in NPP2. A loop adjacent to the nucleotide-binding site, which is disordered in NPP2, is well ordered in NPP1 and might promote nucleotide binding. Remarkably, the N-terminal somatomedin B-like domains of NPP1, unlike those in NPP2, are flexible and do not contact the catalytic domain. Our results provide a structural basis for the nucleotide pyrophosphatase activity of NPP1 and help to understand how disease-causing mutations may affect NPP1 structure and function.
PubMed: 23041369
DOI: 10.1016/J.STR.2012.09.001
PDB entries with the same primary citation
Experimental method
X-RAY DIFFRACTION (3 Å)
Structure validation

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數據於2025-07-02公開中

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