Identification of critical residues of the serotype modifying O-acetyltransferase of Shigella flexneri
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Thanweer, Farzaana; Verma, Naresh K
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BACKGROUND Thirteen serotypes of Shigella flexneri (S. flexneri) have been recognised, all of which are capable of causing bacillary dysentery or shigellosis. With the emergence of the newer S. flexneri serotypes, the development of an effective vaccine has only become more challenging. One of the factors responsible for the generation of serotype diversity is an LPS O-antigen modifying, integral membrane protein known as O-acetyltransferase or Oac. Oac functions by adding an acetyl group to a...[Show more]
dc.contributor.author | Thanweer, Farzaana | |
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dc.contributor.author | Verma, Naresh K | |
dc.date.accessioned | 2016-01-20T03:59:17Z | |
dc.date.available | 2016-01-20T03:59:17Z | |
dc.identifier.issn | 1471-2091 | |
dc.identifier.uri | http://hdl.handle.net/1885/95527 | |
dc.description.abstract | BACKGROUND Thirteen serotypes of Shigella flexneri (S. flexneri) have been recognised, all of which are capable of causing bacillary dysentery or shigellosis. With the emergence of the newer S. flexneri serotypes, the development of an effective vaccine has only become more challenging. One of the factors responsible for the generation of serotype diversity is an LPS O-antigen modifying, integral membrane protein known as O-acetyltransferase or Oac. Oac functions by adding an acetyl group to a specific O-antigen sugar, thus changing the antigenic signature of the parent S. flexneri strain. Oac is a membrane protein, consisting of hydrophobic and hydrophilic components. Oac bears homology to several known and predicted acetyltransferases with most homology existing in the N-terminal transmembrane (TM) regions. RESULTS In this study, the conserved motifs in the TM regions and in hydrophilic loops of S. flexneri Oac were targeted for mutagenesis with the aim of identifying the amino acid residues essential for the function of Oac. We previously identified three critical arginines-R73, R75 and R76 in the cytoplasmic loop 3 of Oac. Re-establishing that these arginines are critical, in this study we suggest a catalytic role for R73 and a structural role for R75 and R76 in O-acetylation. Serine-glycine motifs (SG 52-53, GS 138-139 and SYG 274-276), phenylalanine-proline motifs (FP 78-79 and FPV 282-84) and a tryptophan-threonine motif (WT141-142) found in TM segments and residues RK 110-111, GR 269-270 and D333 found in hydrophilic loops were also found to be critical to Oac function. CONCLUSIONS By studying the effect of the mutations on Oac's function and assembly, an insight into the possible roles played by the chosen amino acids in Oac was gained. The transmembrane serine-glycine motifs and hydrophilic residues (RK 110-111, GR 269-270 and D333) were shown to have an affect on Oac assembly which suggests a structural role for these motifs. The phenylalanine-proline and the tryptophan-threonine motifs affect Oac function which could suggest a catalytic role for these amino acids. | |
dc.description.sponsorship | This work was supported by a grant from the National Health and Medical Research Council of Australia. | |
dc.publisher | BioMed Central | |
dc.rights | © Thanweer and Verma; licensee BioMed Central Ltd. 2012 This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. | |
dc.source | BMC Biochemistry | |
dc.subject | acetyltransferases | |
dc.subject | amino acid motifs | |
dc.subject | amino acid sequence | |
dc.subject | molecular sequence data | |
dc.subject | mutagenesis | |
dc.subject | o antigens | |
dc.subject | protein structure, tertiary | |
dc.subject | recombinant proteins | |
dc.subject | sequence homology, amino acid | |
dc.subject | serotyping | |
dc.subject | shigella flexneri | |
dc.title | Identification of critical residues of the serotype modifying O-acetyltransferase of Shigella flexneri | |
dc.type | Journal article | |
local.description.notes | Imported from ARIES | |
local.identifier.citationvolume | 13 | |
dc.date.issued | 2012-07-15 | |
local.identifier.absfor | 060100 | |
local.identifier.ariespublication | f5625xPUB1427 | |
local.publisher.url | http://www.biomedcentral.com/ | |
local.type.status | Published Version | |
local.contributor.affiliation | Thanweer, Farzaana, College of Medicine, Biology and Environment, CMBE Research School of Biology, Division of Biomedical Science and Biochemistry, The Australian National University | |
local.contributor.affiliation | Verma, Naresh, College of Medicine, Biology and Environment, CMBE Research School of Biology, Division of Biomedical Science and Biochemistry, The Australian National University | |
local.identifier.essn | 1471-2091 | |
local.bibliographicCitation.issue | 1 | |
local.bibliographicCitation.startpage | 13 | |
local.identifier.doi | 10.1186/1471-2091-13-13 | |
dc.date.updated | 2016-02-24T08:46:37Z | |
local.identifier.scopusID | 2-s2.0-84867290439 | |
local.identifier.thomsonID | 000309595800001 | |
Collections | ANU Research Publications |
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