EC Number   |
General Information |
Reference |
|---|
   6.1.2.1 | evolution |
the two amino acid substitutions Q260K/A283E via exchange at nucleotide positions 778 and 848, respectively, in VRSA-9 Ddl lead to the ability to synthesize precursors ending in D-Ala-D-Lac (72%) and D-Ala-D-Ala (21%) in the absence of vancomycin. The VRSA-9 Ddl has an altered D-Ala:D-Ala ligase activity relative to that of VRSA-6 with a Km for D-Ala of 2 mM at subsite 1 and 240 mM at subsite 2. The binding affinity for D-Ala at subsite 2 is 14fold lower than that of VRSA-6. The residues at nucleotide positions 778 and 848 are not conserved among D-Ala:DAla ligases and do not interact directly with the substrates. VRSA-9 Ddl shows the importance of conformational changes in the dimer interface which can indirectly affect the topology of the active site |
-, 715371 |
| 6.1.2.1 | more |
acquisition of vancomycin resistance affects expression of WalRK and PhoPR regulon genes in the phosphate-limited state. Genetic regulation of vancomycin resistance involving also VanA, detailed overview |
-, 716269 |
| 6.1.2.1 | physiological function |
Enterococcus faecium 10/96A from Brazil is resistant to vancomycin with a minimum inhibitory concentration MIC of 0.256 mg/ml. Cytoplasmic peptidoglycan precursors from cells of strain 10/96A grown in the presence or absence of 0.004 mg of vancomycin/ml contain in both cases 95% UDP-MurNAc-pentadepsipeptide, 3% UDPMurNAc-pentapeptide, and 2% UDP-MurNAc-tetrapeptide, supporting the role of VanD4 as a D-Ala-D-Lac ligase and indicating that glycopeptide resistance is expressed constitutively |
-, 707162 |
| 6.1.2.1 | physiological function |
in the presence of vancomycin, production of the VanB D-Ala:D-Lac ligase is induced, which overcomes the defect in the synthesis of peptidoglycan precursors ending in D-AlaD-Ala due to a lack of functional Ddl D-Ala-D-Ala ligase. Vancomycin-dependent strain BM4660 synthesizes mainly UDP-MurNAc-pentadepsipeptide, 44%, whereas large amounts of UDP-MurNActripeptide, 39%, and small amounts of pentapeptide, 12%, and tetrapeptide, 5%, are present. The presence of tripeptide in large quantity suggests that the VanB ligase may not be sufficiently active to synthesize D-AlaD-Lac as rapidly as tripeptide is produced |
-, 707164 |
| 6.1.2.1 | physiological function |
resistance to glycopeptides in Enterococcus faecium BM4416 is due to synthesis of late peptidoglycan precursors ending in D-AlaD-Lac. Strain BM4416 mainly produces UDP-MurNAc-pentadepsipeptide, 69%, terminating in D-AlaD-Lac, UDP-MurNAc-tetrapeptide, 24%, and UDP-MurNAc-tripeptide, 7%. No significant amounts of UDP-MurNAc-pentapeptide are found. Constitutive resistance is encoded by a vanD operon closely related to that of Enterococcus faecium BM4339 and also located in the chromosome. Both VanD-type strains produce an inactivated D-Ala:D-Ala ligase due to an insertion in the ddl gene |
-, 649336 |
| 6.1.2.1 | physiological function |
the enzyme is a key enzyme in the emergence of high level resistance to vancomycin in Enterococcus |
-, 728031 |
| 6.1.2.1 | physiological function |
the vanD gene encodes a D-Ala:D-Lac ligase related to VanA and VanB which is not transferable by conjugation. It renders the cells constitutively resistant to vancomycin with a minimum inhibitory concentration MIC of 0.064 mg/ml and to low levels of teicoplanin, MIC 0.004 mg/ml. Cytoplasmic peptidoglycan precursors that accumulate are mainly UDP-MurNAc-pentadepsipeptide, UDP-MurNAc-tetrapeptide, and UDP-MurNAc-tripeptide. The large proportion of UDP-MurNAc-pentadepsipeptide indicates that the mechanism of vancomycin resistance in BM4339 is similar to that in VanA and VanB strains. The presence of UDP-MurNAc-tripeptide implies that the rate of synthesis of D-AlaD-Ala or D-AlaD-Lac substrates is limiting |
-, 707160 |
| 6.1.2.1 | physiological function |
VanA is a D-alanine:D-alanine ligase of altered substrate specificity. VanA catalyzes ester bond formation between D-alanine and the D-hydroxy acid products of VanH, the best substrate being D-2-hydroxybutyrate. The VanA product D-alanyl-D-2-hydroxybutyrate can then be incorporated into the UDPMurNAc-pentapeptide peptidoglycan precursor |
-, 707463 |
