Please use this identifier to cite or link to this item: http://repositorio.unicamp.br/jspui/handle/REPOSIP/106633
Type: Artigo de periódico
Title: Structural Studies Of Prephenate Dehydratase From Mycobacterium Tuberculosis H37rv By Saxs, Ultracentrifugation, And Computational Analysis
Author: Vivan A.L.
Caceres R.A.
Abrego J.R.B.
Borges J.C.
Neto J.R.
Ramos C.H.I.
De Azevedo Jr. W.F.
Basso L.A.
Santos D.S.
Abstract: Tuberculosis (TB) is one of the most common infectious diseases known to man and responsible for millions of human deaths in the world. The increasing incidence of TB in developing countries, the proliferation of multidrug resistant strains, and the absence of resources for treatment have highlighted the need of developing new drugs against TB. The shikimate pathway leads to the biosynthesis of chorismate, a precursor of aromatic amino acids. This pathway is absent from mammals and shown to be essential for the survival of Mycobacterium tuberculosis, the causative agent of TB. Accordingly, enzymes of aromatic amino acid biosynthesis pathway represent promising targets for structure-based drug design. The first reaction in phenylalanine biosynthesis involves the conversion of chorismate to prephenate, catalyzed by chorismate mutase. The second reaction is catalyzed by prephenate dehydratase (PDT) and involves decarboxylation and dehydratation of prephenate to form phenylpyruvate, the precursor of phenylalanine. Here, we describe utilization of different techniques to infer the structure of M. tuberculosis PDT (MtbPDT) in solution. Small angle X-ray scattering and ultracentrifugation analysis showed that the protein oligomeric state is a tetramer and MtbPDT is a flat disk protein. Bioinformatics tools were used to infer the structure of MtbPDT. A molecular model for MtbPDT is presented and molecular dynamics simulations indicate that MtbPDT is stable. Experimental and molecular modeling results were in agreement and provide evidence for a tetrameric state of MtbPDT in solution. © 2008 Wiley-Liss, Inc.
Editor: 
Rights: fechado
Identifier DOI: 10.1002/prot.22034
Address: http://www.scopus.com/inward/record.url?eid=2-s2.0-51349107793&partnerID=40&md5=0ce6c20c4598a11b0ec426b46c70733c
Date Issue: 2008
Appears in Collections:Unicamp - Artigos e Outros Documentos

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