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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
19
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pubmed:dateCreated |
2010-5-12
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pubmed:abstractText |
Glycosyltransferase enzymes play important roles in numerous cellular pathways. Despite their participation in many therapeutically relevant pathways, there is a paucity of information on how to effectively inhibit this class of enzymes. Here we report that UDP-(5F)-GlcNAc acts as a slow-binding, competitive inhibitor of the retaining glycosyltransferase MshA from Corynebacterium glutamicum (K(i) approximately 1.6 muM). The kinetic data are consistent with a single-step inhibition mechanism whose equilibration is slow relative to catalysis. We believe that this is the first slow-onset inhibitor to be reported for the glycosyltransferase family of enzymes. The potent inhibition of the enzyme by the fluoro-substituted substrate is consistent with the involvement of an oxocarbenium transition-state structure, which has been previously proposed for this family of enzymes. Additionally, although several members of the GT-B enzyme family, including MshA, have been shown to undergo a conformational change upon UDP-GlcNAc binding, the kinetic data are inconsistent with a two-step inhibition mechanism. This suggests that there may be other conformations of the enzyme that are useful for the design of inhibitors against the large family of GT-B glycosyltransferase enzymes.
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pubmed:grant |
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pubmed:commentsCorrections |
http://linkedlifedata.com/resource/pubmed/commentcorrection/20411981-12011052,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20411981-12188668,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20411981-12538870,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20411981-12691742,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20411981-12874381,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20411981-15272305,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20411981-16237703,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20411981-17883281,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20411981-18390549,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20411981-18518825,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20411981-18721881,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20411981-20066263,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20411981-3134344,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20411981-3281418,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20411981-9020780,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20411981-9575336
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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 |
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pubmed:status |
MEDLINE
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pubmed:month |
May
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pubmed:issn |
1520-5126
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pubmed:author |
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pubmed:issnType |
Electronic
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pubmed:day |
19
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pubmed:volume |
132
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
6626-7
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pubmed:dateRevised |
2011-9-26
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pubmed:meshHeading |
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pubmed:year |
2010
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pubmed:articleTitle |
UDP-(5F)-GlcNAc acts as a slow-binding inhibitor of MshA, a retaining glycosyltransferase.
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pubmed:affiliation |
Department of Biochemistry, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, New York 10461, USA. pfrantom@bama.ua.edu
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't,
Research Support, N.I.H., Extramural
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