4Z1C: Structure Of Cadmium Bound Kdo8ps From H.pylori

The crystal structure of 3-deoxy-d-manno-octulosonate-8-phosphate synthase (KDO8PS) from Helicobacter pylori (HpKDO8PS) was determined alone and within various complexes, revealing an extra helix (HE) that is absent in the structures of KDO8PS from other organisms. In contrast to the metal coordination of the KDO8PS enzyme from Aquifex aeolicus, HpKDO8PS is specifically coordinated with Cd(2+) or Zn(2+) ions, and isothermal titration calorimetry (ITC) and differential scanning fluorimetry (DSF) revealed that Cd(2+) thermally stabilizes the protein structure more efficiently than Zn(2+). In the substrate-bound structure, water molecules play a key role in fixing residues in the proper configuration to achieve a compact structure. Using the structures of HpKDO8PS and API [arabinose 5-phosphate (A5P) and phosphoenolpyruvate (PEP) bisubstrate inhibitor], we generated 21 compounds showing potential HpKDO8PS-binding properties via in silico virtual screening. The capacity of three, avicularin, hyperin, and MC181, to bind to HpKDO8PS was confirmed through saturation transfer difference (STD) experiments, and we identified their specific ligand binding modes by combining competition experiments and docking simulation analysis. Hyperin was confirmed to bind to the A5P binding site, primarily via hydrophilic interaction, whereas MC181 bound to both the PEP and A5P binding sites through hydrophilic and hydrophobic interactions. These results were consistent with the epitope mapping by STD. Our results are expected to provide clues for the development of HpKDO8PS inhibitors.
PDB ID: 4Z1CDownload
MMDB ID: 137202
PDB Deposition Date: 2015/3/27
Updated in MMDB: 2016/03
Experimental Method:
x-ray diffraction
Resolution: 1.93  Å
Source Organism:
Similar Structures:
Biological Unit for 4Z1C: dimeric; determined by author and by software (PISA)
Molecular Components in 4Z1C
Label Count Molecule
Proteins (2 molecules)
2-dehydro-3-deoxyphosphooctonate Aldolase(Gene symbol: HP0003)
Molecule annotation
Chemicals (2 molecules)
* Click molecule labels to explore molecular sequence information.

Citing MMDB