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spinqualitylabelsall models PDB ID 2v3q Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image
2v3q, resolution 1.89Å ()
Ligands:	, ,
Evolutionary conservation: Toggle Conservation Colors: Rows = identical sequences: Further Information: Caveats, Explanation, Complete Results at ConSurfDB
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

spinqualitylabelsall models PDB ID 2v3q Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image

HPBP consists of 376 residues with a predicted molecular mass of 38.4 kDa[1]. It contains two similar global domains, connected by a hinge. Each is constituted by a five-stranded β sheet core (three parallel β strands followed by two antiparallel β strands) flanked by . There are two disulfide bridges (C113-C158, C306-C359).

The active site is similar to other phosphate SBPs. The surface of the binding pocket is negative. responsible for the selectivity concerning other negative substrates In total, 8 residues and 13 hydrogen bonds are involved in the binding of the substrate creating a rich network. 12 bonds are formed by dipolar donor groups with 6 backbones NHs (T8, L9, S32, S144, G145, T146) mostly located at the end of 3 helices, 2 NH side chains from R140 and 4 from side chains OHs (T8, S32, S144, T146)

R140 generates two hydrogen bonds with both negative oxygen atoms of the dibasic phosphate. This interaction, by diminishing the charge coupling interaction between the guanidium and phosphate, has previously been described as essential for the fast release of the ionic substrate bound with charged residues.

D61 is the only dipolar acceptor group that makes a hydrogen bond with the only proton available on dibasic phosphate.

The negative surface and the D61 of the HPBP are involved in the specifity towards the phosphate.

ContributorsContributors

Demir Fijuljanin, Christine Ponkratz