1yvb

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{{STRUCTURE_1yvb| PDB=1yvb | SCENE= }}
{{STRUCTURE_1yvb| PDB=1yvb | SCENE= }}
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'''the Plasmodium falciparum Cysteine Protease Falcipain-2'''
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===the Plasmodium falciparum Cysteine Protease Falcipain-2===
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==Overview==
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Falcipain-2 (FP2), the major cysteine protease of the human malaria parasite Plasmodium falciparum, is a hemoglobinase and promising drug target. Here we report the crystal structure of FP2 in complex with a protease inhibitor, cystatin. The FP2 structure reveals two previously undescribed cysteine protease structural motifs, designated FP2(nose) and FP2(arm), in addition to details of the active site that will help focus inhibitor design. Unlike most cysteine proteases, FP2 does not require a prodomain but only the short FP2(nose) motif to correctly fold and gain catalytic activity. Our structure and mutagenesis data suggest a molecular basis for this unique mechanism by highlighting the functional role of two Tyr within FP2(nose) and a conserved Glu outside this motif. The FP2(arm) motif is required for hemoglobinase activity. The structure reveals topographic features and a negative charge cluster surrounding FP2(arm) that suggest it may serve as an exo-site for hemoglobin binding. Motifs similar to FP2(nose) and FP2(arm) are found only in related plasmodial proteases, suggesting that they confer malaria-specific functions.
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(as it appears on PubMed at http://www.pubmed.gov), where 16864794 is the PubMed ID number.
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{{ABSTRACT_PUBMED_16864794}}
==About this Structure==
==About this Structure==
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[[Category: Wang, S X.]]
[[Category: Wang, S X.]]
[[Category: Cysteine protease-inhibitor complex]]
[[Category: Cysteine protease-inhibitor complex]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 16:50:04 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Jul 27 20:46:59 2008''

Revision as of 17:47, 27 July 2008

Image:1yvb.png

Template:STRUCTURE 1yvb

the Plasmodium falciparum Cysteine Protease Falcipain-2

Template:ABSTRACT PUBMED 16864794

About this Structure

1YVB is a Protein complex structure of sequences from Gallus gallus and Plasmodium falciparum 3d7. Full crystallographic information is available from OCA.

Reference

Structural basis for unique mechanisms of folding and hemoglobin binding by a malarial protease., Wang SX, Pandey KC, Somoza JR, Sijwali PS, Kortemme T, Brinen LS, Fletterick RJ, Rosenthal PJ, McKerrow JH, Proc Natl Acad Sci U S A. 2006 Aug 1;103(31):11503-8. Epub 2006 Jul 24. PMID:16864794

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