UniProt functional annotation for P60752



	UniProt functional annotation for P60752

UniProt codes: P60752, P27299.

Organism: Escherichia coli (strain K12).

Taxonomy: Bacteria; Proteobacteria; Gammaproteobacteria; Enterobacterales; Enterobacteriaceae; Escherichia.

Function: Involved in lipopolysaccharide (LPS) biosynthesis. Translocates lipid A-core from the inner to the outer leaflet of the inner membrane (PubMed:8809774, PubMed:9575204, PubMed:12119303, PubMed:15304478, PubMed:28869968). Transmembrane domains (TMD) form a pore in the inner membrane and the ATP-binding domain (NBD) is responsible for energy generation (PubMed:12119303). Shows ATPase activity (PubMed:12119303, PubMed:18024585, PubMed:18344567, PubMed:19132955, PubMed:20412049, PubMed:21462989). May transport glycerophospholipids (PubMed:9575204). In proteoliposomes, mediates the ATP-dependent flipping of a variety of phospholipid and glycolipid derivatives (PubMed:20412049). May also function as a multidrug transporter (PubMed:19132955). {ECO:0000269|PubMed:12119303, ECO:0000269|PubMed:15304478, ECO:0000269|PubMed:18024585, ECO:0000269|PubMed:18344567, ECO:0000269|PubMed:19132955, ECO:0000269|PubMed:20412049, ECO:0000269|PubMed:21462989, ECO:0000269|PubMed:28869968, ECO:0000269|PubMed:8809774, ECO:0000269|PubMed:9575204}.

Catalytic activity: Reaction=ATP + H(2)O + lipid A-core oligosaccharide(Side 1) = ADP + phosphate + lipid A-core oligosaccharide(Side 2).; EC=7.5.2.6; Evidence={ECO:0000255|HAMAP-Rule:MF_01703, ECO:0000269|PubMed:15304478, ECO:0000269|PubMed:20412049, ECO:0000269|PubMed:28869968};

Activity regulation: ATPase activity is stimulated by lipid A, hexaacylated lipid A or Kdo(2)-lipid A (PubMed:12119303, PubMed:18344567). Inhibited by the phosphate analog vanadate (PubMed:12119303, PubMed:18344567, PubMed:28869968). ATPase activity is also modulated by the lipid-based drugs D-20133 and D-21266, along with LY335979 and leupeptin (PubMed:18344567). {ECO:0000269|PubMed:12119303, ECO:0000269|PubMed:18344567, ECO:0000269|PubMed:28869968}.

Biophysicochemical properties: Kinetic parameters: KM=878 uM for ATP {ECO:0000269|PubMed:12119303}; KM=117 uM for ATP {ECO:0000269|PubMed:21462989}; Vmax=37 nmol/min/mg enzyme {ECO:0000269|PubMed:12119303}; Vmax=68 nmol/min/mg enzyme {ECO:0000269|PubMed:21462989};

Subunit: Homodimer. {ECO:0000255|HAMAP-Rule:MF_01703, ECO:0000269|PubMed:17927448, ECO:0000269|PubMed:18024585, ECO:0000269|PubMed:18344567, ECO:0000269|PubMed:19132955, ECO:0000269|PubMed:28869968}.

Subcellular location: Cell inner membrane {ECO:0000255|HAMAP- Rule:MF_01703, ECO:0000269|PubMed:12119303, ECO:0000269|PubMed:15919996, ECO:0000269|PubMed:8809774}; Multi-pass membrane protein {ECO:0000255|HAMAP-Rule:MF_01703, ECO:0000269|PubMed:8809774}.

Domain: In MsbA the ATP-binding domain (NBD) and the transmembrane domain (TMD) are fused. {ECO:0000269|PubMed:17927448, ECO:0000269|PubMed:18024585}.

Domain: Substrate binding induces conformational changes, NBD dimerization, and stabilizes an inward-facing closed pre-translocation state that binds ATP (PubMed:18344567, PubMed:23766512, PubMed:28869968). ATP binding fuels a relative motion of the NBD domains. The movement of the NBDs is coupled to reorientation of the chamber, which binds the lipid substrate, from cytoplasmic-facing to periplasmic-facing through large amplitude motion on either side of the transporter (PubMed:17927448, PubMed:20715055, PubMed:18024585, PubMed:28869968). ATP hydrolysis is then required to resolve the outward-facing conformation back to an inward-facing conformation (PubMed:23766512, PubMed:28869968). The ATP-dependent switch requires robust tetrahelix bundle interactions (PubMed:23306205). {ECO:0000269|PubMed:17927448, ECO:0000269|PubMed:18024585, ECO:0000269|PubMed:18344567, ECO:0000269|PubMed:20715055, ECO:0000269|PubMed:23306205, ECO:0000269|PubMed:23766512, ECO:0000269|PubMed:28869968}.

Domain: Contains two substrate-binding sites that communicate with both the nucleotide-binding domain and with each other. One is a high affinity binding site for the physiological substrate, lipid A, and the other site interacts with drugs with comparable affinity. {ECO:0000269|PubMed:19132955}.

Disruption phenotype: Absence of MsbA alone causes accumulation of hexa-acylated lipid A species and glycerophospholipids in the inner membrane. {ECO:0000269|PubMed:9575204}.

Miscellaneous: In addition to ATP hydrolysis, may utilize another major energy currency in the cell by coupling substrate transport to a transmembrane electrochemical proton gradient (PubMed:27499013). In vitro, MsbA-mediated ethidium efflux is dependent on both the electrochemical proton gradient and ATP hydrolysis (PubMed:27499013). {ECO:0000269|PubMed:27499013}.

Miscellaneous: Identified as a drug target. Inhibited by a series of quinoline compounds that kill E.coli through inhibition of ATPase and transport activity of MsbA. {ECO:0000269|PubMed:30104274}.

Similarity: Belongs to the ABC transporter superfamily. Lipid exporter (TC 3.A.1.106) family. {ECO:0000255|HAMAP-Rule:MF_01703}.

Annotations taken from UniProtKB at the EBI.


Organism:		Escherichia coli (strain K12).
Taxonomy:		Bacteria; Proteobacteria; Gammaproteobacteria; Enterobacterales; Enterobacteriaceae; Escherichia.



Function:		Involved in lipopolysaccharide (LPS) biosynthesis. Translocates lipid A-core from the inner to the outer leaflet of the inner membrane (PubMed:8809774, PubMed:9575204, PubMed:12119303, PubMed:15304478, PubMed:28869968). Transmembrane domains (TMD) form a pore in the inner membrane and the ATP-binding domain (NBD) is responsible for energy generation (PubMed:12119303). Shows ATPase activity (PubMed:12119303, PubMed:18024585, PubMed:18344567, PubMed:19132955, PubMed:20412049, PubMed:21462989). May transport glycerophospholipids (PubMed:9575204). In proteoliposomes, mediates the ATP-dependent flipping of a variety of phospholipid and glycolipid derivatives (PubMed:20412049). May also function as a multidrug transporter (PubMed:19132955). {ECO:0000269\|PubMed:12119303, ECO:0000269\|PubMed:15304478, ECO:0000269\|PubMed:18024585, ECO:0000269\|PubMed:18344567, ECO:0000269\|PubMed:19132955, ECO:0000269\|PubMed:20412049, ECO:0000269\|PubMed:21462989, ECO:0000269\|PubMed:28869968, ECO:0000269\|PubMed:8809774, ECO:0000269\|PubMed:9575204}.


Catalytic activity:		Reaction=ATP + H(2)O + lipid A-core oligosaccharide(Side 1) = ADP + phosphate + lipid A-core oligosaccharide(Side 2).; EC=7.5.2.6; Evidence={ECO:0000255\|HAMAP-Rule:MF_01703, ECO:0000269\|PubMed:15304478, ECO:0000269\|PubMed:20412049, ECO:0000269\|PubMed:28869968};
Activity regulation:		ATPase activity is stimulated by lipid A, hexaacylated lipid A or Kdo(2)-lipid A (PubMed:12119303, PubMed:18344567). Inhibited by the phosphate analog vanadate (PubMed:12119303, PubMed:18344567, PubMed:28869968). ATPase activity is also modulated by the lipid-based drugs D-20133 and D-21266, along with LY335979 and leupeptin (PubMed:18344567). {ECO:0000269\|PubMed:12119303, ECO:0000269\|PubMed:18344567, ECO:0000269\|PubMed:28869968}.
Biophysicochemical properties:		Kinetic parameters: KM=878 uM for ATP {ECO:0000269\|PubMed:12119303}; KM=117 uM for ATP {ECO:0000269\|PubMed:21462989}; Vmax=37 nmol/min/mg enzyme {ECO:0000269\|PubMed:12119303}; Vmax=68 nmol/min/mg enzyme {ECO:0000269\|PubMed:21462989};
Subunit:		Homodimer. {ECO:0000255\|HAMAP-Rule:MF_01703, ECO:0000269\|PubMed:17927448, ECO:0000269\|PubMed:18024585, ECO:0000269\|PubMed:18344567, ECO:0000269\|PubMed:19132955, ECO:0000269\|PubMed:28869968}.
Subcellular location:		Cell inner membrane {ECO:0000255\|HAMAP- Rule:MF_01703, ECO:0000269\|PubMed:12119303, ECO:0000269\|PubMed:15919996, ECO:0000269\|PubMed:8809774}; Multi-pass membrane protein {ECO:0000255\|HAMAP-Rule:MF_01703, ECO:0000269\|PubMed:8809774}.
Domain:		In MsbA the ATP-binding domain (NBD) and the transmembrane domain (TMD) are fused. {ECO:0000269\|PubMed:17927448, ECO:0000269\|PubMed:18024585}.
Domain:		Substrate binding induces conformational changes, NBD dimerization, and stabilizes an inward-facing closed pre-translocation state that binds ATP (PubMed:18344567, PubMed:23766512, PubMed:28869968). ATP binding fuels a relative motion of the NBD domains. The movement of the NBDs is coupled to reorientation of the chamber, which binds the lipid substrate, from cytoplasmic-facing to periplasmic-facing through large amplitude motion on either side of the transporter (PubMed:17927448, PubMed:20715055, PubMed:18024585, PubMed:28869968). ATP hydrolysis is then required to resolve the outward-facing conformation back to an inward-facing conformation (PubMed:23766512, PubMed:28869968). The ATP-dependent switch requires robust tetrahelix bundle interactions (PubMed:23306205). {ECO:0000269\|PubMed:17927448, ECO:0000269\|PubMed:18024585, ECO:0000269\|PubMed:18344567, ECO:0000269\|PubMed:20715055, ECO:0000269\|PubMed:23306205, ECO:0000269\|PubMed:23766512, ECO:0000269\|PubMed:28869968}.
Domain:		Contains two substrate-binding sites that communicate with both the nucleotide-binding domain and with each other. One is a high affinity binding site for the physiological substrate, lipid A, and the other site interacts with drugs with comparable affinity. {ECO:0000269\|PubMed:19132955}.
Disruption phenotype:		Absence of MsbA alone causes accumulation of hexa-acylated lipid A species and glycerophospholipids in the inner membrane. {ECO:0000269\|PubMed:9575204}.
Miscellaneous:		In addition to ATP hydrolysis, may utilize another major energy currency in the cell by coupling substrate transport to a transmembrane electrochemical proton gradient (PubMed:27499013). In vitro, MsbA-mediated ethidium efflux is dependent on both the electrochemical proton gradient and ATP hydrolysis (PubMed:27499013). {ECO:0000269\|PubMed:27499013}.
Miscellaneous:		Identified as a drug target. Inhibited by a series of quinoline compounds that kill E.coli through inhibition of ATPase and transport activity of MsbA. {ECO:0000269\|PubMed:30104274}.
Similarity:		Belongs to the ABC transporter superfamily. Lipid exporter (TC 3.A.1.106) family. {ECO:0000255\|HAMAP-Rule:MF_01703}.