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Article: Enzymatic synthesis and characterizations of cyclic GDP-ribose. A procedure for distinguishing enzymes with ADP-ribosyl cyclase activity

TitleEnzymatic synthesis and characterizations of cyclic GDP-ribose. A procedure for distinguishing enzymes with ADP-ribosyl cyclase activity
Authors
KeywordsChemicals And Cas Registry Numbers
Issue Date1994
PublisherAmerican Society for Biochemistry and Molecular Biology, Inc. The Journal's web site is located at http://www.jbc.org/
Citation
Journal Of Biological Chemistry, 1994, v. 269 n. 48, p. 30260-30267 How to Cite?
AbstractCyclic nucleotides such as cAMP and cGMP are second messengers subserving various signaling pathways. Cyclic ADP-ribose (cADPR), a recently discovered member of the family, is derived from NAD+ and is a mediator of Ca2+ mobilization in various cellular systems. The synthesis and degradation of cADPR are, respectively, catalyzed by ADP-ribosyI cyclase and cADPR hydrolase. CD38, a differentiation antigen of B lymphocytes, has recently been shown to be a bifunctional enzyme catalyzing both the formation and hydrolysis of cADPR. The overall reaction catalyzed by CD38 is the formation of ADP-ribose and nicotinamide from NAD+, identical to that catalyzed by NADase. The difficulties in detecting the formation of cADPR have led to frequent identification of CD38 as a classical NADase. In this study, we show that both ADP-ribosyl cyclase and CD38, but not NADase, can cyclize nicotinamide guanine dinucleotide (NGD+) producing a new nucleotide. Analyses by high performance liquid chromatography and mass spectroscopy indicate the product is cyclic GDP-ribose (cGDPR) with a structure similar to cADPR except with guanine replacing adenine. Compared to cADPR, cGDPR is a more stable compound showing 2.8 times more resistance to heat-induced hydrolysis. These results are consistent with a catalytic scheme for CD38 where the cyclization of the substrate precedes the hydrolytic reaction. Spectroscopic analyses show that cGDPR is fluorescent and has an absorption spectrum different from both NGD+ and GDPR, providing a very convenient way for monitoring its enzymatic formation. The use of NGD+ as substrate for assaying the cyclization reaction was found to be applicable to pure enzymes as well as crude tissue extracts making it a useful diagnostic tool for distinguishing CD38-like enzymes from degradative NADases.
Persistent Identifierhttp://hdl.handle.net/10722/132586
ISSN
2015 Impact Factor: 4.258
2015 SCImago Journal Rankings: 3.151
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorGraeff, RMen_HK
dc.contributor.authorWalseth, TFen_HK
dc.contributor.authorFryxell, Ken_HK
dc.contributor.authorBranton, WDen_HK
dc.contributor.authorHon Cheung Leeen_HK
dc.date.accessioned2011-03-28T09:26:32Z-
dc.date.available2011-03-28T09:26:32Z-
dc.date.issued1994en_HK
dc.identifier.citationJournal Of Biological Chemistry, 1994, v. 269 n. 48, p. 30260-30267en_HK
dc.identifier.issn0021-9258en_HK
dc.identifier.urihttp://hdl.handle.net/10722/132586-
dc.description.abstractCyclic nucleotides such as cAMP and cGMP are second messengers subserving various signaling pathways. Cyclic ADP-ribose (cADPR), a recently discovered member of the family, is derived from NAD+ and is a mediator of Ca2+ mobilization in various cellular systems. The synthesis and degradation of cADPR are, respectively, catalyzed by ADP-ribosyI cyclase and cADPR hydrolase. CD38, a differentiation antigen of B lymphocytes, has recently been shown to be a bifunctional enzyme catalyzing both the formation and hydrolysis of cADPR. The overall reaction catalyzed by CD38 is the formation of ADP-ribose and nicotinamide from NAD+, identical to that catalyzed by NADase. The difficulties in detecting the formation of cADPR have led to frequent identification of CD38 as a classical NADase. In this study, we show that both ADP-ribosyl cyclase and CD38, but not NADase, can cyclize nicotinamide guanine dinucleotide (NGD+) producing a new nucleotide. Analyses by high performance liquid chromatography and mass spectroscopy indicate the product is cyclic GDP-ribose (cGDPR) with a structure similar to cADPR except with guanine replacing adenine. Compared to cADPR, cGDPR is a more stable compound showing 2.8 times more resistance to heat-induced hydrolysis. These results are consistent with a catalytic scheme for CD38 where the cyclization of the substrate precedes the hydrolytic reaction. Spectroscopic analyses show that cGDPR is fluorescent and has an absorption spectrum different from both NGD+ and GDPR, providing a very convenient way for monitoring its enzymatic formation. The use of NGD+ as substrate for assaying the cyclization reaction was found to be applicable to pure enzymes as well as crude tissue extracts making it a useful diagnostic tool for distinguishing CD38-like enzymes from degradative NADases.en_HK
dc.languageengen_US
dc.publisherAmerican Society for Biochemistry and Molecular Biology, Inc. The Journal's web site is located at http://www.jbc.org/en_HK
dc.relation.ispartofJournal of Biological Chemistryen_HK
dc.subjectChemicals And Cas Registry Numbersen_US
dc.titleEnzymatic synthesis and characterizations of cyclic GDP-ribose. A procedure for distinguishing enzymes with ADP-ribosyl cyclase activityen_HK
dc.typeArticleen_HK
dc.identifier.emailGraeff, RM: graeffr@hku.hken_HK
dc.identifier.emailHon Cheung Lee: leehc@hku.hken_HK
dc.identifier.authorityGraeff, RM=rp01464en_HK
dc.identifier.authorityHon Cheung Lee=rp00545en_HK
dc.description.naturelink_to_subscribed_fulltexten_US
dc.identifier.pmid7982936en_HK
dc.identifier.scopuseid_2-s2.0-0027944850en_HK
dc.identifier.volume269en_HK
dc.identifier.issue48en_HK
dc.identifier.spage30260en_HK
dc.identifier.epage30267en_HK
dc.identifier.isiWOS:A1994PU52500036-
dc.publisher.placeUnited Statesen_HK
dc.identifier.scopusauthoridGraeff, RM=7003614053en_HK
dc.identifier.scopusauthoridWalseth, TF=7005424273en_HK
dc.identifier.scopusauthoridFryxell, K=6701731286en_HK
dc.identifier.scopusauthoridBranton, WD=6603252979en_HK
dc.identifier.scopusauthoridHon Cheung Lee=26642959100en_HK

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