Walker A motif, also known as the
Walker loop, or
P-loop, or
phosphate-binding loop, is a motif in
proteins that is associated with
phosphate binding. The motif has the pattern G-x(4)-GK-[TS], where G, K, T and S denote
glycine,
lysine,
threonine and
serine residues respectively, and x denotes any
amino acid. It is present in many
ATP or
GTP utilizing proteins; it is the β phosphate of the
nucleotide that is bound. The
lysine (K) residue in the Walker A motif, together with the main chain NH atoms, are crucial for
nucleotide-binding. It is a
glycine-rich loop preceded by a
beta strand and followed by an
alpha helix; these features are typically part of an α/β domain with four strands sandwiched between two helices on each side. The
phosphate groups of the
nucleotide are also coordinated to a divalent cation such as a
magnesium,
calcium, or
manganese(II) ion. Apart from the conserved lysine, a feature of the P-loop used in phosphate binding is a compound LRLR
nest comprising the four residues xxGK, as above, whose main chain atoms form a phosphate-sized concavity with the NH groups pointing inwards. The synthetic hexapeptide SGAGKT has been shown to bind inorganic phosphate strongly; since such a short peptide does not form an
alpha helix, this suggests that it is the nest, rather than being at the
N-terminus of a helix, that is the main phosphate binding feature. Upon nucleotide hydrolysis the loop does not significantly change the protein
conformation, but stays bound to the remaining phosphate groups. Walker motif A-binding has been shown to cause structural changes in the bound nucleotide, along the line of the
induced fit model of
enzyme binding.
Similar folds PTPs (
protein tyrosine phosphatases) that catalyse the hydrolysis of an inorganic phosphate from a
phosphotyrosine residue (the reverse of a
tyrosine kinase reaction) contain a motif which folds into a P-loop-like structure with an arginine in the place of the conserved lysine. The conserved sequence of this motif is C-x(5)-R-[ST], where C and R denote
cysteine and
arginine residues respectively.
Pyridoxal phosphate (PLP) utilizing enzymes such as
cysteine synthase have also been said to resemble a P-loop.
A-loop The A-loop (
aromatic residue interacting with the
adenine ring of ATP) refers to conserved
aromatic amino acids, essential for ATP-binding, found in about 25 amino acids upstream of the Walker A motif in a subset of P-loop proteins. ==Walker B motif==