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The A‐loop, a novel conserved aromatic acid subdomain upstream of the Walker A motif in ABC transporters, is critical for ATP binding
Author(s) -
Ambudkar Suresh V.,
Kim In-Wha,
Xia Di,
Sauna Zuben E.
Publication year - 2006
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2005.12.051
Subject(s) - atp binding cassette transporter , walker motifs , atp hydrolysis , biochemistry , transporter , atpase , homology modeling , transmembrane domain , transport protein , transmembrane protein , binding site , cyclic nucleotide binding domain , plasma protein binding , biology , chemistry , amino acid , peptide sequence , enzyme , gene , receptor
ATP‐binding cassette (ABC) transporters represent one of the largest families of proteins, and transport a variety of substrates ranging from ions to amphipathic anticancer drugs. The functional unit of an ABC transporter is comprised of two transmembrane domains and two cytoplasmic ABC ATPase domains. The energy of the binding and hydrolysis of ATP is used to transport the substrates across membranes. An ABC domain consists of conserved regions, the Walker A and B motifs, the signature (or C) region and the D, H and Q loops. We recently described the A‐loop ( A romatic residue interacting with the A denine ring of A TP), a highly conserved aromatic residue ∼25 amino acids upstream of the Walker A motif that is essential for ATP‐binding. Here, we review the mutational analysis of this subdomain in human P‐glycoprotein as well as homology modeling, structural and data mining studies that provide evidence for a functional role of the A‐loop in ATP‐binding in most members of the superfamily of ABC transporters.