title: Synthetic peptides corresponding to a repetitive sequence of malarial histidine rich protein bind haem and inhibit haemozoin formation in vitro.
abstract: Synthetic peptides containing a repetitive hexapeptide sequence (Ala-His-His-Ala-Ala-Asp) of malarial histidine-rich protein II were evaluated for binding with haem in vitro. The pattern of haem binding suggested that each repeat unit of this sequence provides one binding site for haem. Chloroquine inhibited the haem-peptide complex formation with preferential formation of a haem chloroquine complex. In vitro studies on haem polymerisation showed that none of the peptides could initiate haemozoin formation. However, they could inhibit haemozoin formation promoted by a malarial parasite extract, possibly by competitively binding free haem. These results indicate this hexapeptide sequence represents the haem binding site of the malarial histidine-rich protein and possibly the site of nucleation for haem polymerisation.
authors.affiliation: Division of Biochemistry, Central Drug Research Institute, Lucknow, India.
authors.forename: A V
authors.initials: AV
authors.lastname: Pandey
authors.forename: R
authors.initials: R
authors.lastname: Joshi
authors.forename: B L
authors.initials: BL
authors.lastname: Tekwani
authors.forename: R L
authors.initials: RL
authors.lastname: Singh
authors.forename: V S
authors.initials: VS
authors.lastname: Chauhan
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000962:Antimalarials / Q000378:metabolism / Q000494:pharmacology; D001665:Binding Sites; D001667:Binding, Competitive; D002738:Chloroquine / Q000378:metabolism / Q000494:pharmacology; D006418:Heme / Q000378:metabolism*; D006420:Hemeproteins / Q000378:metabolism*; D008297:Male; D051379:Mice; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D010961:Plasmodium / Q000737:chemistry*; D011506:Proteins / Q000737:chemistry* / Q000378:metabolism; D015800:Protozoan Proteins / Q000737:chemistry* / Q000378:metabolism; D000099053:Histidine-Rich Glycoprotein
chemical_list: D000962:Antimalarials; D006420:Hemeproteins; D010446:Peptide Fragments; D011506:Proteins; D015800:Protozoan Proteins; D000099053:Histidine-Rich Glycoprotein; C020753:hemozoin; D006418:Heme; D002738:Chloroquine