Linked Life Data

16005528

Source:http://linkedlifedata.com/resource/pubmed/id/16005528

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2005-8-29
pubmed:abstractText
S-adenosylhomocysteine hydrolase is a prospective target for developing new anti-malarial drugs. Inhibition of the hydrolase results in an anti-cellular effect due to the suppression of adenosylmethionine-dependent transmethylations. Based on the crystal structure of Plasmodium falciparum S-adenosylhomocysteine hydrolase which we have determined recently, we performed mutational analyses on P. falciparum and human enzymes. Cys59 and Ala84 of the parasite enzyme, and the equivalent residues on the human enzyme, Thr60 and Gln85, were examined. Mutations of Cys59 and Thr60 caused dramatic impact on inhibition by 2-fluoronoraristeromycin without significant effect both on its kinetic parameters and on inhibition constant against noraristeromycin. In addition, the impact was independent from the electronegativity of the side chain of the substituting residue. These results showed that steric hindrance between a functional group at the 2-position of an adenine nucleoside inhibitor and Thr60 of the human enzyme, not an electrostatic effect, contributed to inhibitor selectivity.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
0166-6851
pubmed:author
pubmed:issnType
Print
pubmed:volume
143
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
146-51
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed:year
2005
pubmed:articleTitle
Mutational analyses of Plasmodium falciparum and human S-adenosylhomocysteine hydrolases.
pubmed:affiliation
Department of Biomolecular Science, Faculty of Engineering, Gifu University, 1-1 Yanagido, Gifu 501-1193, Japan.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't