| Structural, functional, and bioinformatics studies reveal a new snake venom homologue phospholipase A₂ class. | |
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MedLine Citation:
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PMID: 20878713 Owner: NLM Status: In-Process |
Abstract/OtherAbstract:
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Phospholipases A₂ (PLA₂s) are enzymes responsible for membrane disruption through Ca(2+) -dependent hydrolysis of phospholipids. Lys49-PLA₂s are well-characterized homologue PLA₂s that do not show catalytic activity but can exert a pronounced local myotoxic effect. These homologue PLA₂s were first believed to present residual catalytic activity but experiments with a recombinant toxin show they are incapable of catalysis. Herein, we present a new homologue Asp49-PLA₂ (BthTX-II) that is also able to exert muscle damage. This toxin was isolated in 1992 and characterized as presenting very low catalytic activity. Interestingly, this myotoxic homologue Asp49-PLA₂ conserves all the residues responsible for Ca(2+) coordination and of the catalytic network, features thought to be fundamental for PLA₂ enzymatic activity. Previous crystallographic studies of apo BthTX-II suggested this toxin could be catalytically inactive since a distortion in the calcium binding loop was observed. In this article, we show BthTX-II is not catalytic based on an in vitro cell viability assay and time-lapse experiments on C2C12 myotube cell cultures, X-ray crystallography and phylogenetic studies. Cell culture experiments show that BthTX-II is devoid of catalytic activity, as already observed for Lys49-PLA₂s. Crystallographic studies of the complex BthTX-II/Ca(2+) show that the distortion of the calcium binding loop is still present and impairs ion coordination even though Ca(2+) are found interacting with other regions of the protein. Phylogenetic studies demonstrate that BthTX-II is more phylogenetically related to Lys49-PLA₂s than to other Asp49-PLA₂s, thus allowing Crotalinae subfamily PLA₂s to be classified into two main branches: a catalytic and a myotoxic one. |
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Authors:
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Juliana I dos Santos; Mariana Cintra-Francischinelli; Rafael J Borges; Carlos A H Fernandes; Paola Pizzo; Adélia C O Cintra; Antonio S K Braz; Andreimar M Soares; Marcos R M Fontes |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2010-09-27 |
Journal Detail:
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Title: Proteins Volume: 79 ISSN: 1097-0134 ISO Abbreviation: Proteins Publication Date: 2011 Jan |
Date Detail:
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Created Date: 2010-12-01 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 8700181 Medline TA: Proteins Country: United States |
Other Details:
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Languages: eng Pagination: 61-78 Citation Subset: IM |
Copyright Information:
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Copyright © 2010 Wiley-Liss, Inc. |
Affiliation:
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Departamento de Física e Biofísica, Instituto de Biociências, UNESP - Univ Estadual Paulista, Botucatu-SP and Instituto Nacional de Ciência e Tecnologia em Toxinas, CNPq, Brazil. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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