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Literature summary for 1.16.3.1 extracted from
- Structures and metal-binding properties of Helicobacter pylori neutrophil-activating protein with a di-nuclear ferroxidase center (2014), Biomolecules, 4, 600-615 .
Crystallization (Commentary)
| Crystallization (Comment) | Organism |
|---|---|
| crystal structure determination of the enzyme apo form and metal-ion bound forms, such as iron, zinc, and cadmium, of HP-NAP, structure analysis | Helicobacter pylori |
Metals/Ions
| Metals/Ions | Comment | Organism | Structure |
|---|---|---|---|
| Cd2+ | the first cadmium ion, Cd1 is coordinated in a trigonal-bipyramidal manner, in which the triangle is formed by the side chains of His25, Asp52, and a water molecule bridging two cadmium ions, and the corner of the pyramid is formed by the side chain of Glu56 and another water molecule. The second cadmium ion, Cd2 is coordinated in a distorted octahedral manner to the side chain of His37 and three water molecules, with two sites remaining unoccupied. Zinc ions are more likely to coordinate in a tetrahedral arrangement. Cadmium ions are also more likely to coordinate in both tetrahedral and octahedral arrangements, but also exhibit a versatile coordination geometry. Cadmium ions are found to be coordinated in a trigonal-bipyramidal manner | Helicobacter pylori |  |
| Fe2+ | HP-NAP is a dodecameric protein consisting of 17-kDa monomers, and has a spherical shell 9-10 nm in diameter with a hollow central core in which iron ions bind, HP-NAP can bind up to 500 atoms of iron per dodecamer in vitro, structure overview. Two ferroxidase centers are located in the interface of the dimer in Fe-loaded HP-NAP YS39. His25 and His37 of one subunit and Asp52 and Glu56 of the other subunit are chelated to iron ions | Helicobacter pylori | |
| additional information | structures and metal-binding properties of HP-NAP, crystal structure analysis of apoenzyme and enzymes bound to metals Fe2+, Zn2+, and Cd2+, detailed overview.The metal ions bind at the di-nuclear ferroxidase center (FOC) by different coordinating patterns. In comparison with the apo structure, metal loading causes a series of conformational changes in conserved residues among HP-NAP and Dps proteins (Trp26, Asp52, and Glu56) at the di-nuclear ferroxidase center. Trp26, in addition to His25, His37, Asp52, and Glu56, is well conserved among HP-NAPs and Dps proteins, and may play an important role in the conformational changes that occur upon binding of iron ions | Helicobacter pylori | |
| Zn2+ | the first zinc ion, Zn1 is coordinated in a tetrahedral manner to the side chains of His25, Asp52, Glu56, and a water molecule that bridges two zinc ions. The second zinc ion, Zn2 is coordinated in a distorted tetrahedral manner to the side chains of His37, Glu56, and two water molecules | Helicobacter pylori | |
Natural Substrates/ Products (Substrates)
| Natural Substrates | Organism | Comment (Nat. Sub.) | Natural Products | Comment (Nat. Pro.) | Rev. | Reac. |
|---|---|---|---|---|---|---|
| additional information | Helicobacter pylori | the neutrophil-activating protein has a di-nuclear ferroxidase center and shows ferroxidase activity | ? | - |
? | |
| additional information | Helicobacter pylori YS39 | the neutrophil-activating protein has a di-nuclear ferroxidase center and shows ferroxidase activity | ? | - |
? | |
Organism
| Organism | UniProt | Comment | Textmining |
|---|---|---|---|
| Helicobacter pylori | - |
HP-NAP from strain YS39 differs from HP-NAP from strain 26695 at four residues, E46G, V59A, I73L, and Y101H | - |
| Helicobacter pylori YS39 | - |
HP-NAP from strain YS39 differs from HP-NAP from strain 26695 at four residues, E46G, V59A, I73L, and Y101H | - |
Substrates and Products (Substrate)
| Substrates | Comment Substrates | Organism | Products | Comment (Products) | Rev. | Reac. |
|---|---|---|---|---|---|---|
| additional information | the neutrophil-activating protein has a di-nuclear ferroxidase center and shows ferroxidase activity | Helicobacter pylori | ? | - |
? | |
| additional information | the neutrophil-activating protein has a di-nuclear ferroxidase center and shows ferroxidase activity | Helicobacter pylori YS39 | ? | - |
? | |
Subunits
| Subunits | Comment | Organism |
|---|---|---|
| dodecamer | HP-NAP forms a spherical dodecamer with 23 symmetry including two kinds of pores. HP-NAP is a dodecameric protein consisting of 17-kDa monomers, and has a spherical shell 9-10 nm in diameter with a hollow central core in which iron ions bind. The monomer of HP-NAP is composed of a four-helix bundle (helices 1, 2, 3, and 4) with a fifth helix (helix 2-3) of seven residues (Leu69-Leu75) oriented almost perpendicular to the bundle. The monomers of Fe-loaded HP-NAPs from strains YS39 and 26695 are almost identical | Helicobacter pylori |
Synonyms
| Synonyms | Comment | Organism |
|---|---|---|
| Helicobacter pylori neutrophil-activating protein | - |
Helicobacter pylori |
| HP-NAP | - |
Helicobacter pylori |
| More | cf. EC 1.16.3.2 | Helicobacter pylori |
General Information
| General Information | Comment | Organism |
|---|---|---|
| evolution | enzyme HP-NAP belongs to the DNA-protecting proteins under starved conditions (Dps) family, which has significant structural similarities to the dodecameric ferritin family. The overall structure of HP-NAP YS39 is similar to those of other HP-NAPs and Dps proteins | Helicobacter pylori |
| additional information | residues His25, His37, Asp52, and Glu56 are perfectly conserved among HP-NAPs, dodecameric ferritin, and Dps proteins, and play important roles in metal-ion binding | Helicobacter pylori |
| physiological function | neutrophil-activating protein (HP-NAP) is one of a number of virulence factors in Helicobacter pylori. The enzyme promote the adhesion of neutrophils to endothelial cells, and activates NADPH oxidase to produce reactive oxygen species via a cascade of intracellular activation events. HP-NAP binds to the outer membrane surface, which mediates binding to mucin or glycosphingolipids. This protein can also stimulate the production of tissue factor and plasminogen activator inhibitor-2 by human monocytes. HP-NAP can cross the endothelium to promote neutrophil adhesion in vivo and can activate the underlying mast cells. HP-NAP stimulates Th1 immune responses by inducing the production of cytokines, such as interleukin-12 (IL-12) and IL-23. HP-NAP is a major antigen in the immune response to Helicobacter pylori infections. HP-NAP protects Helicobacter pylori from iron-mediated oxidative DNA damage by sequestering free iron, similar to Dps proteins, which protect DNA from oxidative damage | Helicobacter pylori |
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