The C terminus of HspA--a potential target for native Ni(II) and Bi(III) anti-ulcer drugs.
HspA, a protein crucial for nickel homeostasis in Helicobacter pylori (H. pylori), has a unique histidine- and cysteine-rich domain at the C terminus. In this work, we compared the coordination of nickel (the natural co-factor) and bismuth (inhibitor) to this domain (Ac-ACCHDHKKH-NH(2)) and to a reference peptide (Ac-CHCH-NH(2)). Potentiometric, CD, UV-Vis spectroscopic and NMR methods have shown that bismuth binds incomparably stronger than nickel; the same data shows the impact of histidines on such a binding. Our results are in good agreement with earlier biological data and suggest that HspA can be a potential target of the bismuth anti-ulcer drug against H. pylori.
Rowinska-Zyrek
Magdalena
M
Faculty of Chemistry, University of Wrocław, F. Joliot-Curie 14, 50-383, Wroclaw, Poland.
Witkowska
Danuta
D
Valensin
Daniela
D
Kamysz
Wojciech
W
Kozlowski
Henryk
H
D000595:Amino Acid Sequence; D000863:Antacids / Q000494:pharmacology / Q000627:therapeutic use; D000897:Anti-Ulcer Agents / Q000737:chemistry / Q000494:pharmacology*; D001426:Bacterial Proteins / Q000737:chemistry / Q000187:drug effects*; D001665:Binding Sites; D001729:Bismuth / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D002942:Circular Dichroism; D006360:Heat-Shock Proteins / Q000737:chemistry / Q000187:drug effects*; D016481:Helicobacter Infections / Q000188:drug therapy / Q000382:microbiology; D016480:Helicobacter pylori / Q000737:chemistry* / Q000378:metabolism; D006639:Histidine / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D009532:Nickel / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D019906:Nuclear Magnetic Resonance, Biomolecular; D009842:Oligopeptides / Q000737:chemistry / Q000378:metabolism; D011199:Potentiometry; D017434:Protein Structure, Tertiary; D013056:Spectrophotometry, Ultraviolet
D000863:Antacids; D000897:Anti-Ulcer Agents; D001426:Bacterial Proteins; D006360:Heat-Shock Proteins; C113725:HspA protein, bacteria; D009842:Oligopeptides; D006639:Histidine; D009532:Nickel; D001729:Bismuth