Inhibition of alcohol dehydrogenase by bismuth.
Bismuth compounds have been widely used for the treatment of ulcers and Helicobacter pylori infection, and enzyme inhibition was thought to be crucial for bismuth anti-microbial activity. We have investigated the interaction of colloidal bismuth subcitrate (CBS) with alcohol dehydrogenase and our results demonstrate that bismuth can effectively inhibit the enzyme. Kinetic analysis revealed that CBS acted as a non-competitive inhibitor of yeast alcohol dehydrogenase. Both UV-vis and fluorescence data show that interaction of CBS with the enzyme exhibits biphasic processes. Bismuth can replace only half of Zn(II) from the enzyme (i.e., about one Zn(II) per monomer). Surprisingly, binding of CBS also induces the enzyme dissociation from its native form, tetramer into dimers. The inhibition of Bi(III) on the enzyme is probably due to its direct interference with the zinc sites. This study is likely to provide an insight into the mechanism of action of bismuth drugs.
Department of Chemistry and Open Laboratory of Chemical Biology, University of Hong Kong, Pokfulam Road, Hong Kong, PR China.
Lan
L
Jin
Ka-Yee
KY
Szeto
Li
L
Zhang
Weihong
W
Du
Hongzhe
H
Sun
D000426:Alcohol Dehydrogenase / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism*; D000595:Amino Acid Sequence; D000818:Animals; D000890:Anti-Infective Agents / Q000737:chemistry / Q000378:metabolism*; D001729:Bismuth / Q000737:chemistry / Q000378:metabolism*; D004795:Enzyme Stability; D008969:Molecular Sequence Data; D009942:Organometallic Compounds / Q000737:chemistry / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D016415:Sequence Alignment; D015032:Zinc / Q000737:chemistry
D000890:Anti-Infective Agents; D009942:Organometallic Compounds; D029701:Saccharomyces cerevisiae Proteins; D000426:Alcohol Dehydrogenase; C002791:bismuth tripotassium dicitrate; D015032:Zinc; D001729:Bismuth