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Article: Structural studies of intermediates along the cyclization pathway of aplysia ADP-ribosyl cyclase

TitleStructural studies of intermediates along the cyclization pathway of aplysia ADP-ribosyl cyclase
Authors
Keywordscalcium signaling
cyclic ADP-ribose
NAD + cyclization
reaction mechanism
secondary messenger
Issue Date2012
PublisherAcademic Press. The Journal's web site is located at http://www.elsevier.com/locate/jmb
Citation
Journal Of Molecular Biology, 2012, v. 415 n. 3, p. 514-526 How to Cite?
Abstract
Cyclic ADP-ribose (cADPR) is a calcium messenger that can mobilize intracellular Ca 2+ stores and activate Ca 2+ influx to regulate a wide range of physiological processes. Aplysia cyclase is the first member of the ADP-ribosyl cyclases identified to catalyze the cyclization of NAD + into cADPR. The catalysis involves a two-step reaction, the elimination of the nicotinamide ring and the cyclization of the intermediate resulting in the covalent attachment of the purine ring to the terminal ribose. Aplysia cyclase exhibits a high degree of leniency towards the purine base of its substrate, and the cyclization reaction takes place at either the N1- or the N7-position of the purine ring. To decipher the mechanism of cyclization in Aplysia cyclase, we used a crystallization setup with multiple Aplysia cyclase molecules present in the asymmetric unit. With the use of natural substrates and analogs, not only were we able to capture multiple snapshots during enzyme catalysis resulting in either N1 or N7 linkage of the purine ring to the terminal ribose, we were also able to observe, for the first time, the cyclized products of both N1 and N7 cyclization bound in the active site of Aplysia cyclase. © 2011 Elsevier Ltd. All rights reserved.
Persistent Identifierhttp://hdl.handle.net/10722/145586
ISSN
2013 Impact Factor: 3.959
2013 SCImago Journal Rankings: 3.158
ISI Accession Number ID
Funding AgencyGrant Number
Research Grant Council of Hong KongHKU 765909M
HKU 769107M
N_HKU 722/08
National Science Foundation of China
Funding Information:

This work is supported by grants HKU 765909M, HKU 769107M, and N_HKU 722/08 from the Research Grant Council of Hong Kong and the National Science Foundation of China (Q.H., H.C.L., and L.H.Z.). The crystallographic data were collected at the Shanghai Synchrotron Radiation Facility, China, and the National Synchrotron Radiation Research Center, Taiwan, China.

References
Grants

 

DC FieldValueLanguage
dc.contributor.authorKotaka, Men_HK
dc.contributor.authorGraeff, Ren_HK
dc.contributor.authorChen, Zen_HK
dc.contributor.authorZhang, LHen_HK
dc.contributor.authorLee, HCen_HK
dc.contributor.authorHao, Qen_HK
dc.date.accessioned2012-02-28T01:55:54Z-
dc.date.available2012-02-28T01:55:54Z-
dc.date.issued2012en_HK
dc.identifier.citationJournal Of Molecular Biology, 2012, v. 415 n. 3, p. 514-526en_HK
dc.identifier.issn0022-2836en_HK
dc.identifier.urihttp://hdl.handle.net/10722/145586-
dc.description.abstractCyclic ADP-ribose (cADPR) is a calcium messenger that can mobilize intracellular Ca 2+ stores and activate Ca 2+ influx to regulate a wide range of physiological processes. Aplysia cyclase is the first member of the ADP-ribosyl cyclases identified to catalyze the cyclization of NAD + into cADPR. The catalysis involves a two-step reaction, the elimination of the nicotinamide ring and the cyclization of the intermediate resulting in the covalent attachment of the purine ring to the terminal ribose. Aplysia cyclase exhibits a high degree of leniency towards the purine base of its substrate, and the cyclization reaction takes place at either the N1- or the N7-position of the purine ring. To decipher the mechanism of cyclization in Aplysia cyclase, we used a crystallization setup with multiple Aplysia cyclase molecules present in the asymmetric unit. With the use of natural substrates and analogs, not only were we able to capture multiple snapshots during enzyme catalysis resulting in either N1 or N7 linkage of the purine ring to the terminal ribose, we were also able to observe, for the first time, the cyclized products of both N1 and N7 cyclization bound in the active site of Aplysia cyclase. © 2011 Elsevier Ltd. All rights reserved.en_HK
dc.languageengen_US
dc.publisherAcademic Press. The Journal's web site is located at http://www.elsevier.com/locate/jmben_HK
dc.relation.ispartofJournal of Molecular Biologyen_HK
dc.subjectcalcium signalingen_HK
dc.subjectcyclic ADP-riboseen_HK
dc.subjectNAD + cyclizationen_HK
dc.subjectreaction mechanismen_HK
dc.subjectsecondary messengeren_HK
dc.subject.meshADP-ribosyl Cyclase - chemistry - metabolism-
dc.subject.meshAdenosine Diphosphate Ribose - metabolism-
dc.subject.meshAplysia - enzymology-
dc.subject.meshCatalytic Domain-
dc.subject.meshCrystallography, X-Ray-
dc.titleStructural studies of intermediates along the cyclization pathway of aplysia ADP-ribosyl cyclaseen_HK
dc.typeArticleen_HK
dc.identifier.emailKotaka, M: masayo@hku.hken_HK
dc.identifier.emailHao, Q: qhao@hku.hken_HK
dc.identifier.authorityKotaka, M=rp00293en_HK
dc.identifier.authorityHao, Q=rp01332en_HK
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1016/j.jmb.2011.11.022en_HK
dc.identifier.pmid22138343-
dc.identifier.scopuseid_2-s2.0-84855828493en_HK
dc.identifier.hkuros198785en_US
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-84855828493&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume415en_HK
dc.identifier.issue3en_HK
dc.identifier.spage514en_HK
dc.identifier.epage526en_HK
dc.identifier.isiWOS:000300028700006-
dc.publisher.placeUnited Kingdomen_HK
dc.relation.projectChemical synthesis and biological characterizations of antagonists of a novel calcium signaling enzyme - CD38-
dc.relation.projectA new method for macromolecular structure determination: envelope-based phasing-
dc.relation.projectA calcium-signaling pathway mediated by cyclic ADP-ribose and NAADP-
dc.identifier.scopusauthoridKotaka, M=6604073578en_HK
dc.identifier.scopusauthoridGraeff, R=54583462200en_HK
dc.identifier.scopusauthoridChen, Z=37033573500en_HK
dc.identifier.scopusauthoridZhang, LH=15040200600en_HK
dc.identifier.scopusauthoridLee, HC=40761849900en_HK
dc.identifier.scopusauthoridHao, Q=7102508868en_HK
dc.identifier.citeulike10050315-

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