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Literature summary for 7.6.2.2 extracted from

  • Dawson, R.J.; Locher, K.P.
    Structure of a bacterial multidrug ABC transporter (2006), Nature, 443, 180-185 .
    View publication on PubMed
Search for more literature for 7.6.2.2

Cloned(Commentary)

Cloned (Comment) Organism
gene Sav1866, sequence analysis and comparison with other ABC transporters Staphylococcus aureus

Crystallization (Commentary)

Crystallization (Comment) Organism
purified bacterial multidrug ABC transporter, X-ray diffraction structure determination and analysis at 3.0 A resolution Staphylococcus aureus

Localization

Localization Comment Organism GeneOntology No. Textmining
membrane the homodimeric protein consists of 12 transmembrane helices, and integral membrane protein Staphylococcus aureus 16020
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Organism

Organism UniProt Comment Textmining
Staphylococcus aureus Q99T13
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Staphylococcus aureus ATCC 700699 Q99T13
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Staphylococcus aureus Mu50 Q99T13
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Reaction

Reaction Comment Organism Reaction ID
ATP + H2O + xenobiotic[side 1] = ADP + phosphate + xenobiotic[side 2] the structure of Sav1866 reveals that tight interaction of the nucleotide-binding domains in the ATP-bound state is coupled to the outward-facing conformation of the transmembrane domains. In this conformation, bound substrates may escape into the outer leaflet of the lipid bilayer or into the aqueous medium surrounding the cell, depending on their hydrophobicity. Hydrolysis of ATP is expected to return the transporter to an inward-facing conformation, again granting access to the binding site from the cell interior. ABC transporters may thus use an alternating access and release mechanism first postulated for major facilitator transport proteins, with the distinction that ATP binding and hydrolysis, rather than substrate acquisition, may control the conversion of one state into the other Staphylococcus aureus
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Subunits

Subunits Comment Organism
homodimer
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 Staphylococcus aureus

Synonyms

Synonyms Comment Organism
multidrug ABC transporter
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 Staphylococcus aureus
Sav1866
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 Staphylococcus aureus

Cofactor

Cofactor Comment Organism Structure
ADP
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 Staphylococcus aureus
ATP
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 Staphylococcus aureus
additional information although ADP, rather than ATP, is bound, the nucleotide-binding domains in Sav1866 exhibit the conformation of the ATP-bound state Staphylococcus aureus

General Information

General Information Comment Organism
additional information the enzyme consists of 12 transmembrane helices in an arrangement that is consistent with cross-linking studies and electron microscopic imaging of the human multidrug resistance protein MDR1 (UniProt ID P08183), but critically different from that reported for the bacterial lipid flippase MsbA (UniProt ID P60752). The observed, outward-facing conformation reflects the ATP-bound state, with the two nucleotide-binding domains in close contact and the two transmembrane domains forming a central cavity, presumably the drug translocation pathway, that is shielded from the inner leaflet of the lipid bilayer and from the cytoplasm, but exposed to the outer leaflet and the extracellular space. Although ADP, rather than ATP, is bound, the nucleotide-binding domains in Sav1866 exhibit the conformation of the ATP-bound state. Substrate translocation pathway and structrue-function analysis, overview Staphylococcus aureus
physiological function multidrug transporters of the ABC family facilitate the export of diverse cytotoxic drugs across cell membranes Staphylococcus aureus