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Structure-Function of Falcipains: Malarial Cysteine Proteases

Evidence indicates that cysteine proteases play essential role in malaria parasites; therefore an obvious area of investigation is the inhibition of these enzymes to treat malaria. Studies with cysteine protease inhibitors and manipulating cysteine proteases genes have suggested a role for cysteine...

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Detalles Bibliográficos
Autores principales: Pandey, Kailash C., Dixit, Rajnikant
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Hindawi Publishing Corporation 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3317066/
https://www.ncbi.nlm.nih.gov/pubmed/22529862
http://dx.doi.org/10.1155/2012/345195
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author Pandey, Kailash C.
Dixit, Rajnikant
author_facet Pandey, Kailash C.
Dixit, Rajnikant
author_sort Pandey, Kailash C.
collection PubMed
description Evidence indicates that cysteine proteases play essential role in malaria parasites; therefore an obvious area of investigation is the inhibition of these enzymes to treat malaria. Studies with cysteine protease inhibitors and manipulating cysteine proteases genes have suggested a role for cysteine proteases in hemoglobin hydrolysis. The best characterized Plasmodium cysteine proteases are falcipains, which are papain family enzymes. Falcipain-2 and falcipain-3 are major hemoglobinases of P. falciparum. Structural and functional analysis of falcipains showed that they have unique domains including a refolding domain and a hemoglobin binding domain. Overall, the complexes of falcipain-2 and falcipain-3 with small and macromolecular inhibitors provide structural insight to facilitate the design or modification of effective drug treatment against malaria. Drug development targeting falcipains should be aided by a strong foundation of biochemical and structural studies.
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spelling pubmed-33170662012-04-23 Structure-Function of Falcipains: Malarial Cysteine Proteases Pandey, Kailash C. Dixit, Rajnikant J Trop Med Review Article Evidence indicates that cysteine proteases play essential role in malaria parasites; therefore an obvious area of investigation is the inhibition of these enzymes to treat malaria. Studies with cysteine protease inhibitors and manipulating cysteine proteases genes have suggested a role for cysteine proteases in hemoglobin hydrolysis. The best characterized Plasmodium cysteine proteases are falcipains, which are papain family enzymes. Falcipain-2 and falcipain-3 are major hemoglobinases of P. falciparum. Structural and functional analysis of falcipains showed that they have unique domains including a refolding domain and a hemoglobin binding domain. Overall, the complexes of falcipain-2 and falcipain-3 with small and macromolecular inhibitors provide structural insight to facilitate the design or modification of effective drug treatment against malaria. Drug development targeting falcipains should be aided by a strong foundation of biochemical and structural studies. Hindawi Publishing Corporation 2012 2012-02-19 /pmc/articles/PMC3317066/ /pubmed/22529862 http://dx.doi.org/10.1155/2012/345195 Text en Copyright © 2012 K. C. Pandey and R. Dixit. https://creativecommons.org/licenses/by/3.0/ This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Review Article
Pandey, Kailash C.
Dixit, Rajnikant
Structure-Function of Falcipains: Malarial Cysteine Proteases
title Structure-Function of Falcipains: Malarial Cysteine Proteases
title_full Structure-Function of Falcipains: Malarial Cysteine Proteases
title_fullStr Structure-Function of Falcipains: Malarial Cysteine Proteases
title_full_unstemmed Structure-Function of Falcipains: Malarial Cysteine Proteases
title_short Structure-Function of Falcipains: Malarial Cysteine Proteases
title_sort structure-function of falcipains: malarial cysteine proteases
topic Review Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3317066/
https://www.ncbi.nlm.nih.gov/pubmed/22529862
http://dx.doi.org/10.1155/2012/345195
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