A conformational analysis of Walker motif A [GXXXXGKT (S)] in nucleotide-binding and other proteins

Abstract

The sequence GXXXXGKT/S, popularly known as Walker motif A, is widely believed to be the site for binding nucleotides in many proteins. Examination of the crystal structures in the Protein Data Bank showed that about half of the examples having these sequences do not bind or use nucleotides. Data analyses showed 92 different Walker sequences of the variable quartet (XXXX). Ramachandran angles in this segment revealed conformational similarity in the group of 45 proteins, known to bind or utilize nucleotides. The conformations of this segment in other proteins differ widely and it is not known whether they play any role in their functions. A flip of a peptide unit at different locations, with little change in the backbone conformation was noted in nine pairs of these proteins having same Walker sequence. An examination of the immediate neighborhood of the Walker sequence indicates that this region is preceded by a beta-strand and followed by an alpha-helix, resulting in the motif beta-W-alpha, an invariant feature amongst nucleotide-binding proteins.

TRIM29 regulates the assembly of DNA repair proteins into damaged chromatin

“…The Walker A motif is a nucleotide-binding motif that is highly conserved in numerous ATPases 35 . Previous studies revealed that the lysine residue forms a hydrogen bond with oxygen of g-phosphate of ATP and that the serine/threonine residues interact with Mg ion 36,37 . To determine whether TRIM29 has ATP-and ADP-binding abilities, we generated FLAG-TRIM29 WT and a K54A/S55A mutant in which both Lys54 and Ser55 were substituted with Ala. K54A and S55A mutations abrogated the binding of TRIM29 to ATP and ADP (Fig.…”

The MIDASIN and NOTCHLESS genes are essential for female gametophyte development in Arabidopsis thaliana

“…AtMDN1, like its yeast ortholog, is thus most probably localized in the nucleus. (Ramakrishnan et al 2002). Short consensus sequences are indicated under the alignment.…”

PKA and the Structural Kinome

“…A distinguishing feature of the EPKs is a Glycinerich Loop (G-Loop) that lies between the first two beta strands. This is quite distinct from the P-Loop or Walker Motif that is found in hexokinase and other ATPases, where the g-phosphate of ATP is buried under the P-Loop at the base of the cleft that lies between the two lobes (57). In the EPKs the adenine ring of ATP is buried under the G-Loop at the base of the cleft between the N-Lobe and the C-lobe while the g-phosphate is positioned at the edge of the cleft and is more solvent exposed.…”