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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
Pt 1
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pubmed:dateCreated |
2001-1-26
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pubmed:abstractText |
Highly purified Aplysia californica ADP-ribosyl cyclase was found to be a multifunctional enzyme. In addition to the known transformation of NAD(+) into cADP-ribose this enzyme is able to catalyse the solvolysis (hydrolysis and methanolysis) of cADP-ribose. This cADP-ribose hydrolase activity, which becomes detectable only at high concentrations of the enzyme, is amplified with analogues such as pyridine adenine dinucleotide, in which the cleavage rate of the pyridinium-ribose bond is much reduced compared with NAD(+). Although the specificity ratio V(max)/K(m) is in favour of NAD(+) by 4 orders of magnitude, this multifunctionality allowed us to propose a 'partitioning' reaction scheme for the Aplysia enzyme, similar to that established previously for mammalian CD38/NAD(+) glycohydrolases. This mechanism involves the formation of a single oxocarbenium-type intermediate that partitions to cADP-ribose and solvolytic products via competing pathways. In favour of this mechanism was the finding that the enzyme also catalysed the hydrolysis of NMN(+), a substrate that cannot undergo cyclization. The major difference between the mammalian and the invertebrate enzymes resides in their relative cyclization/hydrolysis rate-constant ratios, which dictate their respective yields of cADP-ribose (ADP-ribosyl cyclase activity) and ADP-ribose (NAD(+) glycohydrolase activity). For the Aplysia enzyme's catalysed transformation of NAD(+) we favour a mechanism where the formation of cADP-ribose precedes that of ADP-ribose; i.e. macroscopically the invertebrate ADP-ribosyl cyclase conforms to a sequential reaction pathway as a limiting form of the partitioning mechanism.
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pubmed:commentsCorrections |
http://linkedlifedata.com/resource/pubmed/commentcorrection/10861229-10400320,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10861229-10413485,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10861229-10521467,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10861229-10600637,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10861229-1471258,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10861229-1650254,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10861229-1650255,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10861229-1830494,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10861229-203460,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10861229-2466645,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10861229-3496336,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10861229-6279,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10861229-7775378,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10861229-7941427,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10861229-7980606,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10861229-7982936,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10861229-8235624,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10861229-8250903,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10861229-8391778,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10861229-8395705,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10861229-8527487,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10861229-8798630,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10861229-8901875,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10861229-9193683,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10861229-9211328,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10861229-9354813,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10861229-9494110,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10861229-9748331,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10861229-9858777
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/ADP-ribosyl Cyclase,
http://linkedlifedata.com/resource/pubmed/chemical/Adenosine Diphosphate,
http://linkedlifedata.com/resource/pubmed/chemical/Antigens, CD,
http://linkedlifedata.com/resource/pubmed/chemical/Antigens, CD38,
http://linkedlifedata.com/resource/pubmed/chemical/Antigens, Differentiation,
http://linkedlifedata.com/resource/pubmed/chemical/Methanol,
http://linkedlifedata.com/resource/pubmed/chemical/NAD,
http://linkedlifedata.com/resource/pubmed/chemical/NAD Nucleosidase
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pubmed:status |
MEDLINE
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pubmed:month |
Jul
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pubmed:issn |
0264-6021
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
1
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pubmed:volume |
349
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
203-10
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pubmed:dateRevised |
2009-11-18
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pubmed:meshHeading |
pubmed-meshheading:10861229-ADP-ribosyl Cyclase,
pubmed-meshheading:10861229-Adenosine Diphosphate,
pubmed-meshheading:10861229-Animals,
pubmed-meshheading:10861229-Antigens, CD,
pubmed-meshheading:10861229-Antigens, CD38,
pubmed-meshheading:10861229-Antigens, Differentiation,
pubmed-meshheading:10861229-Aplysia,
pubmed-meshheading:10861229-Chromatography, High Pressure Liquid,
pubmed-meshheading:10861229-Dose-Response Relationship, Drug,
pubmed-meshheading:10861229-Electrophoresis, Polyacrylamide Gel,
pubmed-meshheading:10861229-Kinetics,
pubmed-meshheading:10861229-Methanol,
pubmed-meshheading:10861229-Models, Biological,
pubmed-meshheading:10861229-Models, Chemical,
pubmed-meshheading:10861229-NAD,
pubmed-meshheading:10861229-NAD+ Nucleosidase,
pubmed-meshheading:10861229-Time Factors
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pubmed:year |
2000
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pubmed:articleTitle |
Unifying mechanism for Aplysia ADP-ribosyl cyclase and CD38/NAD(+) glycohydrolases.
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pubmed:affiliation |
Laboratoire de Chimie Bioorganique, UMR 7514 CNRS-ULP, Faculté de Pharmacie, 74 route du Rhin, 67400 Strasbourg-Illkirch, France.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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