File Download

There are no files associated with this item.

  Links for fulltext
     (May Require Subscription)
Supplementary

Article: Inhibition of urease by bismuth(III): Implications for the mechanism of action of bismuth drugs

TitleInhibition of urease by bismuth(III): Implications for the mechanism of action of bismuth drugs
Authors
KeywordsBismuth
Inhibition
Nuclear magnetic resonance spectroscopy
Urease
UV-vis spectroscopy
Issue Date2006
PublisherSpringer New York LLC. The Journal's web site is located at http://springerlink.metapress.com/openurl.asp?genre=journal&issn=0966-0844
Citation
Biometals, 2006, v. 19 n. 5, p. 503-511 How to Cite?
AbstractBismuth compounds are widely used for the treatment of peptic ulcers and Helicobacter pylori infections. It has been suggested that enzyme inhibition plays an important role in the antibacterial activity of bismuth towards this bacterium. Urease, an enzyme that converts urea into ammonia and carbonic acid, is crucial for colonization of the acidic environment of the stomach by H. pylori. Here, we show that three bismuth complexes exhibit distinct mechanisms of urease inhibition, with some differences dependent on the source of the enzyme. Bi(EDTA) and Bi(Cys) 3 are competitive inhibitors of jack bean urease with K i values of 1.74 ± 0.14 and 1.84 ± 0.15 mM, while the anti-ulcer drug, ranitidine bismuth citrate (RBC) is a non-competitive inhibitor with a K i value of 1.17 ± 0.09 mM. A 13C NMR study showed that Bi(Cys) 3 reacts with jack bean urease during a 30 min incubation, releasing free cysteines from the metal complex. Upon incubation with Bi(EDTA) and RBC, the number of accessible cysteine residues in the homohexameric plant enzyme decreased by 5.80 ± 0.17 and 11.94 ± 0.13, respectively, after 3 h of reaction with dithiobis(2-nitrobenzoic acid). Kinetic analysis showed that Bi(EDTA) is both a competitive inhibitor and a time-dependent inactivator of the recombinant Klebsiella aerogenes urease. The active C319A mutant of the bacterial enzyme displays a significantly reduced sensitivity toward inactivation by Bi(EDTA) compared with the wild-type enzyme, consistent with binding of Bi 3+ to the active site cysteine (Cys 319) as the mechanism of enzyme inactivation. © Springer 2006.
Persistent Identifierhttp://hdl.handle.net/10722/68784
ISSN
2015 Impact Factor: 2.134
2015 SCImago Journal Rankings: 0.733
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorZhang, Len_HK
dc.contributor.authorMulrooney, SBen_HK
dc.contributor.authorLeung, AFKen_HK
dc.contributor.authorZeng, Yen_HK
dc.contributor.authorKo, BBCen_HK
dc.contributor.authorHausinger, RPen_HK
dc.contributor.authorSun, Hen_HK
dc.date.accessioned2010-09-06T06:07:42Z-
dc.date.available2010-09-06T06:07:42Z-
dc.date.issued2006en_HK
dc.identifier.citationBiometals, 2006, v. 19 n. 5, p. 503-511en_HK
dc.identifier.issn0966-0844en_HK
dc.identifier.urihttp://hdl.handle.net/10722/68784-
dc.description.abstractBismuth compounds are widely used for the treatment of peptic ulcers and Helicobacter pylori infections. It has been suggested that enzyme inhibition plays an important role in the antibacterial activity of bismuth towards this bacterium. Urease, an enzyme that converts urea into ammonia and carbonic acid, is crucial for colonization of the acidic environment of the stomach by H. pylori. Here, we show that three bismuth complexes exhibit distinct mechanisms of urease inhibition, with some differences dependent on the source of the enzyme. Bi(EDTA) and Bi(Cys) 3 are competitive inhibitors of jack bean urease with K i values of 1.74 ± 0.14 and 1.84 ± 0.15 mM, while the anti-ulcer drug, ranitidine bismuth citrate (RBC) is a non-competitive inhibitor with a K i value of 1.17 ± 0.09 mM. A 13C NMR study showed that Bi(Cys) 3 reacts with jack bean urease during a 30 min incubation, releasing free cysteines from the metal complex. Upon incubation with Bi(EDTA) and RBC, the number of accessible cysteine residues in the homohexameric plant enzyme decreased by 5.80 ± 0.17 and 11.94 ± 0.13, respectively, after 3 h of reaction with dithiobis(2-nitrobenzoic acid). Kinetic analysis showed that Bi(EDTA) is both a competitive inhibitor and a time-dependent inactivator of the recombinant Klebsiella aerogenes urease. The active C319A mutant of the bacterial enzyme displays a significantly reduced sensitivity toward inactivation by Bi(EDTA) compared with the wild-type enzyme, consistent with binding of Bi 3+ to the active site cysteine (Cys 319) as the mechanism of enzyme inactivation. © Springer 2006.en_HK
dc.languageengen_HK
dc.publisherSpringer New York LLC. The Journal's web site is located at http://springerlink.metapress.com/openurl.asp?genre=journal&issn=0966-0844en_HK
dc.relation.ispartofBioMetalsen_HK
dc.subjectBismuthen_HK
dc.subjectInhibitionen_HK
dc.subjectNuclear magnetic resonance spectroscopyen_HK
dc.subjectUreaseen_HK
dc.subjectUV-vis spectroscopyen_HK
dc.titleInhibition of urease by bismuth(III): Implications for the mechanism of action of bismuth drugsen_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=0966-0844&volume=19&spage=503&epage=511&date=2006&atitle=Inhibition+of+urease+by+bismuth(III):+Implications+for+the+mechanism+of+action+of+bismuth+drugsen_HK
dc.identifier.emailSun, H:hsun@hkucc.hku.hken_HK
dc.identifier.authoritySun, H=rp00777en_HK
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1007/s10534-005-5449-0en_HK
dc.identifier.pmid16937256-
dc.identifier.scopuseid_2-s2.0-33747885475en_HK
dc.identifier.hkuros121166en_HK
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-33747885475&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume19en_HK
dc.identifier.issue5en_HK
dc.identifier.spage503en_HK
dc.identifier.epage511en_HK
dc.identifier.isiWOS:000240098000006-
dc.publisher.placeUnited Statesen_HK
dc.identifier.scopusauthoridZhang, L=8085225300en_HK
dc.identifier.scopusauthoridMulrooney, SB=6602189568en_HK
dc.identifier.scopusauthoridLeung, AFK=23100193400en_HK
dc.identifier.scopusauthoridZeng, Y=7402981405en_HK
dc.identifier.scopusauthoridKo, BBC=49761664400en_HK
dc.identifier.scopusauthoridHausinger, RP=7006147474en_HK
dc.identifier.scopusauthoridSun, H=7404827446en_HK

Export via OAI-PMH Interface in XML Formats


OR


Export to Other Non-XML Formats