Vancomycin Resisitance

Question 1

How is binding of vancomycin transfereds

Answer 1

Upon activation of VanS by a sensory ligand VanS undergoes at a histidine autophosphorylation residue (His164).
Transfer of the phosphate group to an aspartate group on VanR (Asp53) results in a conformational change on VanR to promote dimerization and DNA binding.
Binding of phospho-VanR to the pro vanH,A,X promotes, results in transcriptional activationphospho-VanR binding to the VanRS promotor respresses thsi

Question 2

How does Van H contribute to resisitance

Answer 2

synthesis lactate for use of Van A

Question 3

How does Van X contribute

Answer 3

VanX cleave any D-ala-d-ala

Question 4

How does Van A contribute

Answer 4

e VanA
family synthesizes predominantly D-Ala–D-Lac by selec
tively
activating D-lactate while discriminating against
D
-Ala2

Question 5

Mechanism of Van A

Answer 5

one mechanism that VanA uses to minimize the amount of D-Ala–D-Ala is to reject the protonated form of D-Ala (main form of D ala)
His244 to Ala mutation
His 244 responsible for binding- large km change in ATP second binding site, not change in kCat
His244 and Arg242 appeared partially responsible for the rejection of the protonated form of D-Alaat subsite 2 His244 sidechain positions in the active site such that the protonated imidazole ring could help reject the protonated D- Ala2