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Article: Structural basis for the mechanistic understanding of human CD38-controlled multiple catalysis

TitleStructural basis for the mechanistic understanding of human CD38-controlled multiple catalysis
Authors
Issue Date2006
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, 2006, v. 281 n. 43, p. 32861-32869 How to Cite?
AbstractThe enzymatic cleavage of the nicotinamide-glycosidic bond on nicotinamide adenine dinucleotide (NAD+) has been proposed to go through an oxocarbenium ion-like transition state. Because of the instability of the ionic intermediate, there has been no structural report on such a transient reactive species. Human CD38 is an ectoenzyme that can use NAD+ to synthesize two calcium-mobilizing molecules. By using NAD+ and a surrogate substrate, NGD+, we captured and determined crystal structures of the enzyme complexed with an intermediate, a substrate, and a product along the reaction pathway. Our results showed that the intermediate is stabilized by polar interactions with the catalytic residue Glu226 rather than by a covalent linkage. The polar interactions between Glu226 and the substrate 2′,3′-OH groups are essential for initiating catalysis. Ser193 was demonstrated to have a regulative role during catalysis and is likely to be involved in intermediate stabilization. In addition, a product inhibition effect by ADP-ribose (through the reorientation of the product) or GDP-ribose (through the formation of a covalently linked GDP-ribose dimer) was observed. These structural data provide insights into the understanding of multiple catalysis and clues for drug design. © 2006 by The American Society for Biochemistry and Molecular Biology, Inc.
Persistent Identifierhttp://hdl.handle.net/10722/91902
ISSN
2015 Impact Factor: 4.258
2015 SCImago Journal Rankings: 3.151
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorLiu, Qen_HK
dc.contributor.authorKriksunov, IAen_HK
dc.contributor.authorGraeff, Ren_HK
dc.contributor.authorMunshi, Cen_HK
dc.contributor.authorHon, CLen_HK
dc.contributor.authorHao, Qen_HK
dc.date.accessioned2010-09-17T10:30:02Z-
dc.date.available2010-09-17T10:30:02Z-
dc.date.issued2006en_HK
dc.identifier.citationJournal Of Biological Chemistry, 2006, v. 281 n. 43, p. 32861-32869en_HK
dc.identifier.issn0021-9258en_HK
dc.identifier.urihttp://hdl.handle.net/10722/91902-
dc.description.abstractThe enzymatic cleavage of the nicotinamide-glycosidic bond on nicotinamide adenine dinucleotide (NAD+) has been proposed to go through an oxocarbenium ion-like transition state. Because of the instability of the ionic intermediate, there has been no structural report on such a transient reactive species. Human CD38 is an ectoenzyme that can use NAD+ to synthesize two calcium-mobilizing molecules. By using NAD+ and a surrogate substrate, NGD+, we captured and determined crystal structures of the enzyme complexed with an intermediate, a substrate, and a product along the reaction pathway. Our results showed that the intermediate is stabilized by polar interactions with the catalytic residue Glu226 rather than by a covalent linkage. The polar interactions between Glu226 and the substrate 2′,3′-OH groups are essential for initiating catalysis. Ser193 was demonstrated to have a regulative role during catalysis and is likely to be involved in intermediate stabilization. In addition, a product inhibition effect by ADP-ribose (through the reorientation of the product) or GDP-ribose (through the formation of a covalently linked GDP-ribose dimer) was observed. These structural data provide insights into the understanding of multiple catalysis and clues for drug design. © 2006 by The American Society for Biochemistry and Molecular Biology, Inc.en_HK
dc.languageengen_HK
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.rightsJournal of Biological Chemistry. Copyright © American Society for Biochemistry and Molecular Biology, Inc.-
dc.subject.meshAmino Acid Substitution-
dc.subject.meshAntigens, CD38 - chemistry - isolation and purification - metabolism-
dc.subject.meshGlutamic Acid - metabolism-
dc.subject.meshGuanosine Diphosphate Sugars - metabolism-
dc.subject.meshNAD+ Nucleosidase - metabolism-
dc.titleStructural basis for the mechanistic understanding of human CD38-controlled multiple catalysisen_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=0021-9258&volume=281&issue=43&spage=32861–32869&epage=&date=2006&atitle=Structural+basis+for+the+mechanistic+understanding+human+CD38-controlled+multiple+catalysis-
dc.identifier.emailGraeff, R: graeffr@hku.hken_HK
dc.identifier.emailHon, CL: leehc@hku.hken_HK
dc.identifier.emailHao, Q: qhao@hku.hken_HK
dc.identifier.authorityGraeff, R=rp01464en_HK
dc.identifier.authorityHon, CL=rp00545en_HK
dc.identifier.authorityHao, Q=rp01332en_HK
dc.description.naturelink_to_OA_fulltext-
dc.identifier.doi10.1074/jbc.M606365200en_HK
dc.identifier.pmid16951430-
dc.identifier.scopuseid_2-s2.0-33845936792en_HK
dc.identifier.hkuros135021-
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-33845936792&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume281en_HK
dc.identifier.issue43en_HK
dc.identifier.spage32861en_HK
dc.identifier.epage32869en_HK
dc.identifier.isiWOS:000241414500084-
dc.publisher.placeUnited Statesen_HK
dc.identifier.scopusauthoridLiu, Q=35215401600en_HK
dc.identifier.scopusauthoridKriksunov, IA=6507909504en_HK
dc.identifier.scopusauthoridGraeff, R=7003614053en_HK
dc.identifier.scopusauthoridMunshi, C=7003972383en_HK
dc.identifier.scopusauthoridHon, CL=26642959100en_HK
dc.identifier.scopusauthoridHao, Q=7102508868en_HK

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