Walker A motif

The physical basis of the kinetic linkage between GTP hydrolysis and conformational change arises from the involvement of Switch I and Switch II in both processes. The P-loop, or Walker A motif (Walker et at, 1982)... 

The characteristic (consensus) sequence ofP-loops (the Walker A motif Walker et al., 1982) is Gly-x-x-x-x-Gly-Lys-Thr/Ser (the region in red in Fig. 5) this sequence is often used in bioinformatic searches to identify proteins related to this family. Each myosin and kinesin has a single P-loop. For example, Dictyostelium myosin II has the sequence as in Fig. 5 (179) G-E-S-G-A-G-K-T (186). On the other hand, dynein, with a heavy chain that partly forms a ringlike core complex of six AAA+ domains, has P-loop motifs in the first four of these domains (e.g., G-P-A-G-P-G-K-T). There may be a complex series of interactions between these various sites to generate movement, but the P-loop in the third domain has been shown to be essential for dynein motor function (Silvanovich et al., 2003). 

Walker A Motif A motif described in SKN-1, a transcription factor in Caenorhabditis ele-gans. See Walker, A.K., See, R., Batchelder, C. et al., A conserved transcription motif suggesting functional parallels between Caenorhabitis ele-gans SKN-1 and Cap n Collar-related basic leucine zipper proteins, J. Biol. Chem. 275, 22166-22171, 2000. 

Sister chromatid cohesion is primarily established by the cohesin complex (23). The cohesin complex is a multiprotein complex that contains the structural maintenance of chromosomes (SMC) family of proteins (24). SMC proteins contain the Walker A motif at their N-termini and the Walker B motif at their C-termini (Fig. 2a). These motifs are brought together by an intramolecular coiled-coil domain to form a functional ATPase domain, which is similar to other ATP-binding cassette (ABC) ATPases, such as RAD50 (25). SMC proteins... 

The NBD unit harbors several conserved sequence motifs (Walker A and B, ABC-signature motifs), which... 

The ATPase activity of FhuC was originally claimed on the basis of the presence of the Walker A and Walker B consensus motif si and the location of FhuC... 

The characteristic Walker A and Walker B motifs that are involved in ATP binding [144] are always found in the ATPase or ABC domains. In addition, a signature motif, also called the LSGGQ motif, is typical of all bacterial ABC domains involved in binding-protein-dependent import. The signature motif is absent in other types of ATPases. 

Loo, T.W., Bartlett, M.C. and Clarke, D. M. (2002) The LSGGQ motif in each nucleotide-binding domain of human P-glycoprotein is adjacent to the opposing walker A sequence. Journal of Biological Chemistry, 277, 41303-41306. 

It is important to note that P-gp inhibition by a compound for the efflux of any of these ligands does not directly correlate with the ability of P-gp to efflux the compound of interest (177). Such is the case with paclitaxel, which is considered to be an excellent P-gp substrate but a poor inhibitor as determined by the dye-efflux method. The converse is seen with progesterone, which is a good inhibitor of P-gp-mediated efflux and yet is a poor substrate. It is important to note that P-gp inhibition can occur in several ways—competitively, non-competitively, and via inhibition of ATP hydrolysis at the Walker A and B motifs (271). Furthermore, the false negatives due to poor permeability noted for transport assays can also produce false negatives in these interaction assays. 

All ABC proteins contain at least three characteristic peptide sequences the Walker A and B motifs, and the so-called ABC-signature sequence. Whereas the Walker motifs are present in several classes of ATP-binding pro-... 

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