Linked Life Data

15383297

Source:http://linkedlifedata.com/resource/pubmed/id/15383297

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2004-9-22
pubmed:abstractText
The enzyme hypoxanthine-guanine phosphorybosyltransferase (HGPRT) in the malarial parasite Plasmodium falciparum (Pf) is central to the salvage pathway for purine nucleotide biosynthesis and is a potential antimalarial chemotherapeutic target. The pH profile of the enzyme activity using xanthine as a substrate shows the possible involvement of a histidine residue in the activity of the enzyme. Chemical modification studies using diethylpyrocarbonate (DEPC) also corroborate this hypothesis. A comparative sequence alignment of Pf HGPRT with the human, Tricomonus foetus and Toxoplasma gondii HGPRT, coupled with the 3D structural alignment between these enzymes indicated that a histidine residue at position 196 of the Pf HGPRT sequence was located in the close proximity to the active site. Site directed mutagenesis of this histidine residue to lysine (the corresponding residue in the human enzyme) specifically abrogated xanthine and guanine utilization of the enzyme without affecting the conversion of hypoxanthine to its corresponding nucleotide. The mechanism of action for this enzyme was evaluated by steady state kinetics for the substrates xanthine, guanine and PRPP and product inhibition studies. The results indicate the possibility of ping-pong mechanism for the enzyme in contrast to the ternary complex mechanism followed by the human enzyme. These results show that the difference in human and malarial HGPRT can be gainfully exploited to design specific inhibitor for this enzyme.
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
137
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
267-76
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
2004
pubmed:articleTitle
Biochemical characterization of Plasmodium falciparum hypoxanthine-guanine-xanthine phosphorybosyltransferase: role of histidine residue in substrate selectivity.
pubmed:affiliation
AstraZeneca R & D, Bellary Road, Hebbal, Bangalore 560024, India.
pubmed:publicationType
Journal Article, In Vitro