Linked Life Data

2015290

Source:http://linkedlifedata.com/resource/pubmed/id/2015290

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
1991-5-23
pubmed:abstractText
The final step of hypusine formation in the eukaryotic translation initiation factor 4D (eIF-4D) is mediated by the enzyme deoxyhypusyl hydroxylase. In an effort to find specific inhibitors for this enzyme, we have studied the effects of two catecholpeptides, N alpha-acetyl-N delta-(3,4-dihydroxybenzoyl)-L-Orn-L-Pro-Gly (compound I) and N alpha-acetyl-N delta-(2,3-dihydroxybenzoyl)-L-Orn-L-Pro-Gly (compound II). Their structures were designed for anchorage to the enzyme s active site, utilizing the catechol-mediated chelation of a putative, enzyme-bound metal ion. Both compounds were found to strongly inhibit hypusine formation in vitro. Compound I was about seven times more potent than compound II, whereas the component peptide itself showed no intrinsic inhibitory activity even at concentrations as high as 1 mM. When used in conjugation with a chelating catechol moiety, however, it gave a 17- and an 8-fold enhancement of the half-maximal inhibition mediated by the chelating moieties per se, i.e. the 3,4- and the 2,3-dihydroxybenzoyl esters, respectively. The mode of inhibition by compound I was competitive with respect to the unhydroxylated precursor of eIF-4D and showed a Ki value of 32 microM +/- 3.4 microM. These catecholpeptides are the most efficient peptide antagonists of deoxyhypusyl hydroxylase known at present. They allow an assessment of the enzyme's active site organization and provide the first experimental evidence that a metal ion constitutes an integral part of its catalytic center.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
0006-3002
pubmed:author
pubmed:issnType
Print
pubmed:day
8
pubmed:volume
1077
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
159-66
pubmed:dateRevised
2003-11-14
pubmed:meshHeading
pubmed:year
1991
pubmed:articleTitle
The active site of deoxyhypusyl hydroxylase: use of catecholpeptides and their component chelator and peptide moieties as molecular probes.
pubmed:affiliation
Dipartimento di Biochimica e Biofisica, I Facoltà di Medicina, Università di Napoli, Italy.
pubmed:publicationType
Journal Article