GxxxxGKTS

GxxxxGKTS is a short, highly conserved sequence motif found in a broad family of nucleotide-binding proteins. It is a variant of the Walker A or P-loop motif, which coordinates nucleotide binding and hydrolysis. The canonical pattern is described as GxxxxGKT/S, indicating a glycine-rich loop followed by another glycine, a lysine, and a terminal residue that is either threonine or serine. The specific form GxxxxGKTS denotes a variant in which a serine follows the threonine, a minor but observed divergence in some proteins.

Functionally, the motif forms the phosphate-binding loop (P-loop) that interacts with the beta and gamma phosphates of bound nucleotides such as GTP or ATP. The lysine residue helps coordinate the phosphates, while the threonine/serine participates in catalytic and conformational roles, including coordination of a divalent metal ion such as Mg2+. This arrangement is essential for nucleotide binding and efficient hydrolysis, enabling conformational changes that drive molecular function in the associated protein.

Distribution and significance: GxxxxGKTS is found across many members of the P-loop NTPase superfamily, including small GTPases (such as Ras-like proteins), various kinases and motor proteins, and multiple ATPases. Its conservation reflects a fundamental mechanism for coupling nucleotide state to catalytic activity. Because the motif underpins nucleotide binding, mutations that disrupt the interface—particularly at the conserved lysine or surrounding residues—can impair function and are often detrimental to the biological role of the protein.