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Hemozoin formation in malaria: a two-step process involving histidine-rich proteins and lipids.

Abstract：

:Major blood stage antimalarial drugs like chloroquine and artemisinin target the heme detoxification process of the malaria parasite. Hemozoin formation reactions in vitro using the Plasmodium falciparum histidine-rich protein-2 (Pfhrp-2), lipids, and auto-catalysis are slow and could not explain the speed of detoxification needed for parasite survival. Here, we show that malarial hemozoin formation is a coordinated two component process involving both lipids and histidine-rich proteins. Hemozoin formation efficiency in vitro is 1-2% with Pfhrp-2 and 0.25-0.5% with lipids. We added lipids after 9h in a 12h Pfhrp-2 mediated reaction that resulted in sixfold increase in hemozoin formation. However, a lipid mediated reaction in which Pfhrp-2 was added after 9h produced only twofold increase in hemozoin production compared to the reaction with Pfhrp-2 alone. Synthetic peptides corresponding to the Pfhrp-2 heme binding sequences, based on repeats of AHHAAD, neither alone nor in combination with lipids were able to generate hemozoin in vitro. These results indicate that hemozoin formation in malaria parasite involves both the lipids and the scaffolding proteins. Histidine-rich proteins might facilitate hemozoin formation by binding with a large number of heme molecules, and facilitating the dimer formation involving iron-carboxylate bond between two heme molecules, and lipids may then subsequently assist the mechanism of long chain formation, held together by hydrogen bonds or through extensive networking of hydrogen bonds.

journal_name

Biochem Biophys Res Commun

journal_title

Biochemical and biophysical research communications

authors

Pandey AV,Babbarwal VK,Okoyeh JN,Joshi RM,Puri SK,Singh RL,Chauhan VS

doi

10.1016/s0006-291x(03)01465-7

subject

Has Abstract

pub_date

2003-09-05 00:00:00

pages

736-43

issue

4

eissn

0006-291X

issn

1090-2104

pii

S0006291X03014657

journal_volume

308

pub_type

杂志文章

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