Use this URL to cite or link to this record in EThOS: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.596145
Title: Molecular mechanism of resistance to vancomycin in Enterococcus gallinarum
Author: Arias, C. A.
Awarding Body: University of Cambridge
Current Institution: University of Cambridge
Date of Award: 2000
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Abstract:
The vanC cluster of Enterococcus gallinarum BM4174 contains five genes: vanC-1, vanXYC, vanT, vanRc and vanSC. Three genes are sufficient for vancomycin resistance: vanC-1 encodes a ligase that synthesises the dipeptide D-Ala-D-Ser for addition to UDP-MurNAc-tripeptide; vanXYC encodes a D,D-dipeptidase/carboxypeptidase that hydrolyses D-Ala-D-Ala and removes D-Ala from UDP-MurNAc-pentapeptide[D-Ala], and vanT encodes a membrane-bound serine racemase that provides D-Ser for the synthetic pathway. The three genes are clustered: the start codons of vanXYC and vanT overlap the termination codon of vanC-1 and vanXYC respectively. The serine racemase VanT is a 698 amino acid polypeptide with an amino terminal domain containing ten predicted transmembrane segments. The protein contains a highly conserved pyridoxal phosphate attachment site in the C-terminal domain, typical of alanine racemases. Comparative modelling of the deduced C-terminal domain was based on the alignment of VanT with the Alr alanine racemase from Bacillus stearothermophilus. The model reveals that almost all critical amino acids in the active site of Alr are conserved in VanT, indicating that the C-terminal domain of VanT is likely to adopt a three-dimensional structure similar to that of Alr and that the protein could exist as a dimer. The purified soluble domain of VanT also exhibited both serine and alanine racemase activities. Two genes which encodes proteins with homology to the VanS-VanR two-component regulatory system are present downstream from the resistance genes. All residues with important functions in response regulators and histidine kinases are conserved in VanRC and VanSC respectively.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.596145  DOI: Not available
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