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https://hdl.handle.net/1822/15982
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Campo DC | Valor | Idioma |
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dc.contributor.author | Pessoa, Joana Sá | - |
dc.contributor.author | Silva, Isabel Soares | - |
dc.contributor.author | Myrianthopoulos, Vassilios | - |
dc.contributor.author | Mikros, Emmanuel | - |
dc.contributor.author | Diallinas, George | - |
dc.contributor.author | Casal, Margarida | - |
dc.date.accessioned | 2011-12-29T09:54:57Z | - |
dc.date.available | 2011-12-29T09:54:57Z | - |
dc.date.issued | 2011 | - |
dc.identifier.uri | https://hdl.handle.net/1822/15982 | - |
dc.description.abstract | Lactic, acetic and propionic acids have been used for many years in industrial and pharmaceutical companies. In Saccharomyces cerevisiae, Jen1p is a major monocarboxylate:H+ symporter specific primarily for lactate, pyruvate and for acetate (TC # 2.A.1.12.2) (Casal et al., 1999). A phylogenetic tree of ScJen1p homologues (Casal et al., 2008) showed the existence of two main clusters: a Jen1 group (monocarboxylate transporters) and a Jen2-like (dicarboxylate transporters). Structure-function relationships in Jen1p have been approached by using a rational mutational analysis of conserved amino acid residues (Soares-Silva et al., 2007). Analysis of the conserved sequence 379NXX[S/T]HX[S/T]QDXXXT391, located in transmembrane segment seven (TMS-VII), showed that residues N379, H383 or D387 are necessary for function and specificity, while Q386 is important for the kinetics of Jen1p-mediated transport. In this work, we rationally designed and analyzed novel mutations in conserved regions located in TMS-II, TMS-V and TMS-XI of Jen1p, which we predicted to affect Jen1p specificity (distinction between mono and dicarboxylates) and function. Among the residues studied, F270 (TMS-V) and Q498 (TMS-XI) are specificity determinants for the distinction of mono- from dicarboxylates, and N501 (TMS-XI) is critical for function. Using a model based on Jen1p similarity with the GlpT permease, we show that all polar residues critical for function within TMS-VII and TMS-XI are aligned along the protein pore and substrate docking studies reveal a potential substrate translocation trajectory consisting mostly of the polar residues genetically identified as important for function. Overall, our results constitute a first step towards the genetic manipulation of substrate specificity in the lactate/pyruvate:H+ symporter subfamily and a tool for the in silico prediction of the function of Jen1p homologues in other fungi (Soares-Silva et al., 2011). | por |
dc.description.sponsorship | I.S.S. (SFRH/BPD/22976/2005) and J.S.P. (SFRH/BD/61530/2009) received fellowships from FCT | por |
dc.language.iso | eng | por |
dc.relation | info:eu-repo/grantAgreement/FCT/SFRH/SFRH%2FBPD%2F22976%2F2005/PT | - |
dc.relation | info:eu-repo/grantAgreement/FCT/SFRH/SFRH%2FBD%2F61530%2F2009/PT | - |
dc.rights | openAccess | por |
dc.title | Identification of amino acid residues critical for the substrate translocation in lactate permease JEN1p of saccharomyces cerevisiae | por |
dc.type | conferenceAbstract | - |
dc.peerreviewed | no | por |
sdum.publicationstatus | Not Published | por |
oaire.citationConferenceDate | 01 - 03 Dez. 2011 | por |
oaire.citationConferencePlace | Braga, Portugal | por |
oaire.citationTitle | MicroBiotec11 | por |
sdum.conferencePublication | MicroBiotec11 | por |
Aparece nas coleções: | DBio - Comunicações/Communications in Congresses |
Ficheiros deste registo:
Ficheiro | Descrição | Tamanho | Formato | |
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Identification of amino acid residues critical for the substrate translocation in lactate permease Jen1p of Saccharomyces cerevisiae.pdf | 87,5 kB | Adobe PDF | Ver/Abrir |