Matches in SemOpenAlex for { <https://semopenalex.org/work/W838449852> ?p ?o ?g. }
Showing items 1 to 51 of
51
with 100 items per page.
- W838449852 abstract "Gram-negative bacteria possess tripartite pumps, composed of a membrane fusion protein (MFP), an inner membrane protein (IMP) and an outer membrane protein (OMP), to transport drugs across the inner and outer membranes. The plasmid encoding MacA, MacB and TolC confers resistance to the macrolide erythromycin in the host E. coli cell Kam3, indicating the three proteins are assembled and actively functional. MFPs are believed to have an important role in the stabilizing the pump complex; intriguingly, we found that the MFP MacA not only interacts directly with the IMP MacB and the OMP TolC, but regulates the function of MacB, apparently increasing its affinity for both ATP and erythromycin. As MacB hydrolyzes ATP there is a burst in phosphate production that is symptomatic of the reaction being rate- limited by product release; but the burst disappeared in the presence of MacA. Since MacA caused only a marginal increase in the k(_cat), but a significant decrease in the Km, for the steady-state ATPase activity, this suggests that the disappearance of the phosphate burst is due to a decrease in the rate of hydrolysis, rather than an increase in the rate of product release. This kinetic behaviour indicates that MacA promotes and stabilizes the ATP-binding form of the transporter. MacA regulates the activity of MacB via its ẞ-strand domain since S. aureus MacA, which lacks the coiled coil structure that is present in E. coli MacA and believed to be involved in the interaction with TolC, was able to abolish the Pi burst catalysed by MacB, in direct analogy with the effect of E. coli MacA on MacB. Analytical ultracentrifugation, mass spectrometry and atomic force microscopy indicated that MacB forms dimers, in analogy to ABC- transporters that require a pair of NBDs to bind ATP. Our data suggests a direct role for MacA in facilitating the delivery of drugs by MacB to TolC: by enhancing the binding of drugs to MacB and stabilizing the reorientation of MacB to the outward- facing conformation." @default.
- W838449852 created "2016-06-24" @default.
- W838449852 creator A5049605588 @default.
- W838449852 date "2008-01-01" @default.
- W838449852 modified "2023-09-27" @default.
- W838449852 title "Characterisation of the MacA/MacB/TolC tripartite pump that confers resistance to macrolides in E. coli" @default.
- W838449852 hasPublicationYear "2008" @default.
- W838449852 type Work @default.
- W838449852 sameAs 838449852 @default.
- W838449852 citedByCount "0" @default.
- W838449852 crossrefType "dissertation" @default.
- W838449852 hasAuthorship W838449852A5049605588 @default.
- W838449852 hasConcept C104317684 @default.
- W838449852 hasConcept C12554922 @default.
- W838449852 hasConcept C141315368 @default.
- W838449852 hasConcept C144647389 @default.
- W838449852 hasConcept C146587185 @default.
- W838449852 hasConcept C181199279 @default.
- W838449852 hasConcept C185592680 @default.
- W838449852 hasConcept C23265538 @default.
- W838449852 hasConcept C41625074 @default.
- W838449852 hasConcept C547475151 @default.
- W838449852 hasConcept C55493867 @default.
- W838449852 hasConcept C86803240 @default.
- W838449852 hasConcept C95444343 @default.
- W838449852 hasConceptScore W838449852C104317684 @default.
- W838449852 hasConceptScore W838449852C12554922 @default.
- W838449852 hasConceptScore W838449852C141315368 @default.
- W838449852 hasConceptScore W838449852C144647389 @default.
- W838449852 hasConceptScore W838449852C146587185 @default.
- W838449852 hasConceptScore W838449852C181199279 @default.
- W838449852 hasConceptScore W838449852C185592680 @default.
- W838449852 hasConceptScore W838449852C23265538 @default.
- W838449852 hasConceptScore W838449852C41625074 @default.
- W838449852 hasConceptScore W838449852C547475151 @default.
- W838449852 hasConceptScore W838449852C55493867 @default.
- W838449852 hasConceptScore W838449852C86803240 @default.
- W838449852 hasConceptScore W838449852C95444343 @default.
- W838449852 hasLocation W8384498521 @default.
- W838449852 hasOpenAccess W838449852 @default.
- W838449852 hasPrimaryLocation W8384498521 @default.
- W838449852 hasRelatedWork W1982778966 @default.
- W838449852 hasRelatedWork W2061856372 @default.
- W838449852 hasRelatedWork W2121915984 @default.
- W838449852 hasRelatedWork W2131435269 @default.
- W838449852 hasRelatedWork W2289123319 @default.
- W838449852 hasRelatedWork W2790418666 @default.
- W838449852 isParatext "false" @default.
- W838449852 isRetracted "false" @default.
- W838449852 magId "838449852" @default.
- W838449852 workType "dissertation" @default.