Linked Life Data

16568996

Source:http://linkedlifedata.com/resource/pubmed/id/16568996

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
13
pubmed:dateCreated
2006-3-29
pubmed:abstractText
Very potent inhibitors were synthesized for the enzymatic deacetylation of N-acetyl-d-glucosamine-6-phosphate (NagA) and N-acetyl-d-glutamate (DGD). The methyl phosphonamidate derivative of d-glucosamine-6-phosphate bound to N-acetyl-d-glucosamine-6-phosphate deacetylase with an equilibrium dissociation constant of 34 +/- 5 nM at pH 7.5 and an association rate constant of 6.1 x 103 M-1 s-1. The inhibition constant is 4000-fold lower than the Michaelis constant for the substrate N-acetyl-d-glucosamine-6-phosphate. N-Acetyl-d-glutamate deacetylase was inhibited by the methyl phosphonamidate derivative of d-glutamate with an inhibition constant of 460 +/- 70 pM at pH 7.6. The inhibitor bound to the enzyme 500 000-fold tighter than the Michaelis constant for N-formyl-d-glutamate. These compounds mimic the putative tetrahedral intermediate formed upon nucleophilic attack of an activated water molecule on the amide bond of the target substrate. These inhibitors should prove useful in the elucidation of the enzyme-substrate interactions for enzymes within the amidohydrolase superfamily.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
0002-7863
pubmed:author
pubmed:issnType
Print
pubmed:day
5
pubmed:volume
128
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
4244-5
pubmed:dateRevised
2008-1-17
pubmed:meshHeading
pubmed:year
2006
pubmed:articleTitle
Tight binding inhibitors of N-acyl amino sugar and N-acyl amino acid deacetylases.
pubmed:affiliation
Department of Chemistry, Texas A&M University, College Station, 77842-3012, USA.
pubmed:publicationType
Journal Article, Research Support, N.I.H., Extramural