Linked Life Data

16448128

Source:http://linkedlifedata.com/resource/pubmed/id/16448128

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
2006-2-1
pubmed:abstractText
A set of N-acylated, carboxyamide fluorotyrosine (F(n)()Y) analogues [Ac-3-FY-NH(2), Ac-3,5-F(2)Y-NH(2), Ac-2,3-F(2)Y-NH(2), Ac-2,3,5-F(3)Y-NH(2), Ac-2,3,6-F(3)Y-NH(2) and Ac-2,3,5,6-F(4)Y-NH(2)] have been synthesized from their corresponding amino acids to interrogate the detailed reaction mechanism(s) accessible to F(n)()Y*s in small molecules and in proteins. These Ac-F(n)()Y-NH(2) derivatives span a pK(a) range from 5.6 to 8.4 and a reduction potential range of 320 mV in the pH region accessible to most proteins (6-9). DFT electronic-structure calculations capture the observed trends for both the reduction potentials and pK(a)s. Dipeptides of the methyl ester of 4-benzoyl-l-phenylalanyl-F(n)()Ys at pH 4 were examined with a nanosecond laser pulse and transient absorption spectroscopy to provide absorption spectra of F(n)()Y*s. The EPR spectrum of each F(n)()Y* has also been determined by UV photolysis of solutions at pH 11 and 77 K. The ability to vary systematically both pK(a) and radical reduction potential, together with the facility to monitor radical formation with distinct absorption and EPR features, establishes that F(n)()Ys will be useful in the study of biological charge-transport mechanisms involving tyrosine. To demonstrate the efficacy of the fluorotyrosine method in unraveling charge transport in complex biological systems, we report the global substitution of tyrosine by 3-fluorotyrosine (3-FY) in the R2 subunit of ribonucleotide reductase (RNR) and present the EPR spectrum along with its simulation of 3-FY122*. In the companion paper, we demonstrate the utility of F(n)()Ys in providing insight into the mechanism of tyrosine oxidation in biological systems by incorporating them site-specifically at position 356 in the R2 subunit of Escherichia coli RNR.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
0002-7863
pubmed:author
pubmed:issnType
Print
pubmed:day
8
pubmed:volume
128
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1569-79
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
2006
pubmed:articleTitle
Mono-, di-, tri-, and tetra-substituted fluorotyrosines: new probes for enzymes that use tyrosyl radicals in catalysis.
pubmed:affiliation
Department of Chemistry, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, Massachusetts 02139-4307, USA.
pubmed:publicationType
Journal Article, Research Support, N.I.H., Extramural