Sandbox Reserved 703
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| 2v3q, resolution 1.89Å () | |||||||||
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| Ligands: | , , | ||||||||
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| Resources: | FirstGlance, OCA, RCSB, PDBsum | ||||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||||
DescriptionDescription
HPBP is a 38kDa apoliprotein, and belongs to the family of ubiquitous eukaryotic proteins named DING, an extracellular protein family including four conserved amino acids at its N-terminal end. It is the only known transporter capable of binding phosphate ions in the human plasma. HPBP is bound to PON1, a Ca-dependent enzyme associated to HDL (High Density Lipoprotein), another lipoprotein which enables lipids like cholesterol and triglycerides to be transported from the blood to the liver. It is the place where it can be removed, reducing the amount of arterial cholesterol. HPBP is always copurified with the enzyme paraoxonase (PON1), that is why it was always ignored before 2006. The copurification is the result of a similar molecular weight, strong hydrophobic interactions, and the fact that PON1 is a glycosylated protein. The separation of the two molecules involves a hydroxyapatite chromatography with phosphate concentration gradient elution. Up to now, HPBP has never been characterized or predicted from nucleic acid databases of human genome. Its X-ray structure is similar to the prokaryotic phosphate solute binding proteins (SBPs) associated with ATP binding cassette transmembrane transporters. Their role is to enable the unidirectional transport of substances trough the membrane, using ATP hydrolysis.
Activity and physiological functionsActivity and physiological functions
HPBP is associated in vivo with PON1, and binds inorganic phosphate ions. During some experiments, it was possible to show that the separation of HPBP and PON1 involves a fast denaturing of the two proteins, which means that the PON1/HPBP complex is essential for each other’s stability. The different oligomeric organisations of the PON1/HPBP complex depend on the calcium, phosphate and detergent concentrations.Therefore, this complex is implicated in the phosphocalcic metabolism. Normally, the phosphate concentration should always be around 0.5-1.0 mM, hence HPBP is always saturated with phosphate. The existence of a phosphate detector in human plasma, associated with a lipoprotein, demonstrate the necessity to avoid the direct contact between phosphate and calcium. Indeed, hyperphosphatemia is a risk factor for cardio vascular diseases.
StructureStructure
ApplicationsApplications
External ResourcesExternal Resources
ContributorsContributors
Demir Fijuljanin, Christine Ponkratz