Publication Date:
2002-12-10
Description:
Cysteine proteases of Plasmodium falciparum are required for survival of the malaria parasite, yet their specific cellular functions remain unclear. We used a chemical proteomic screen with a small-molecule probe to characterize the predominant cysteine proteases throughout the parasite life cycle. Only one protease, falcipain 1, was active during the invasive merozoite stage. Falcipain 1-specific inhibitors, identified by screening of chemical libraries, blocked parasite invasion of host erythrocytes, yet had no effect on normal parasite processes such as hemoglobin degradation. These results demonstrate a specific role for falcipain 1 in host cell invasion and establish a potential new target for antimalarial therapeutics.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Greenbaum, Doron C -- Baruch, Amos -- Grainger, Munira -- Bozdech, Zbynek -- Medzihradszky, Katlin F -- Engel, Juan -- DeRisi, Joseph -- Holder, Anthony A -- Bogyo, Matthew -- MC_U117532067/Medical Research Council/United Kingdom -- New York, N.Y. -- Science. 2002 Dec 6;298(5600):2002-6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Pharmaceutical Chemistry, Veterans Affairs Medical Center, University of California, San Francisco, CA 94143, USA. dgreenb@itsa.ucsf.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/12471262" target="_blank"〉PubMed〈/a〉
Keywords:
Animals
;
Cysteine Endopeptidases/isolation & purification/*metabolism
;
Cysteine Proteinase Inhibitors/chemistry/pharmacology
;
Dose-Response Relationship, Drug
;
Erythrocytes/*parasitology
;
Fluorescent Antibody Technique
;
Hemoglobins/metabolism
;
Humans
;
Leucine/*analogs & derivatives/pharmacology
;
Life Cycle Stages
;
Organelles/enzymology
;
Plasmodium falciparum/drug effects/*enzymology/growth &
;
development/*pathogenicity
;
Proteomics
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
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