ATP ‐binding Motifs

Abstract

Adenosine 5′‐triphosphate (ATP) binds to a great number of proteins to elicit a wide variety of effects, including energy production and molecular signalling. Proteins have evolved different strategies to specifically recognize ATP, utilizing different ways of binding the phosphoryl moieties as well as the adenine base. The most common, conserved sequence and structural motif for binding ATP is the Walker‐A motif, or P‐loop, found in many different protein structural families. Greater variation in the sequence of the P‐loop is being recognized, as more ATP‐binding proteins are being structurally and functionally characterized. In contrast to the P‐loop, recognition of the adenine base often makes use of conserved structural motifs of main‐chain atoms via hydrogen‐bonding interactions, or side‐chains in stacking interactions, without a definitive amino acid sequence pattern. Key concepts: A major class of ATP‐binding proteins are those that contain a P‐loop or Walker‐A motif. P‐loops or glycine‐rich loops function by binding the phosphoryl groups of ATP. Several sequence variations on the Walker‐A motif are now known and have been functionally characterized. The Walker‐B motif contains a conserved acidic residue (Glu/Asp) that functions to bind directly or indirectly a metal ion important in catalysis. Adenine‐binding does not occur through specific sequence motifs, but rather uses a conserved pattern of polar and nonpolar interactions within a structural motif. Both main‐chain hydrogen bonding and aromatic residue stacking contribute to adenine‐binding by proteins.

Evidence that Na+/H+ exchanger 1 is an ATP‐binding protein

“…Collectively, these results suggest that the adenine ring and γ‐phosphoryl group of ATP are important determinants for nucleotide binding to NHE1. The best‐known ATP‐binding sequence is called the phosphate‐binding loop motif or the Walker‐A motif ( G X 4 G K[ S / T ] as originally identified) . Recently, several sequence variations derived from this motif have been reported .…”

“…The best‐known ATP‐binding sequence is called the phosphate‐binding loop motif or the Walker‐A motif ( G X 4 G K[ S / T ] as originally identified) . Recently, several sequence variations derived from this motif have been reported . Both the γ‐phosphoryl group and the adenine ring were critical for nucleotide recognition of proteins, and of them interacted with the basic residues of the R (X 2–3 ) R or K (X 2–3 ) K motifs .…”

Conservation and Variation in Strategies for DNA Replication of Kinetoplastid Nuclear Genomes

“…1B , insert box). Within the AAA+ ATPase domain, conserved Walker A and B motifs (fundamental components of the ATP-binding site and essential for ATPase activity) and a signature arginine finger (involved in ATP hydrolysis of the adjacent AAA+ ATPase subunit in the protein complex) are needed to modulate ORC activity [ 32 , 33 ]. In contrast, Orc6 appears to have evolved independently and does not possess any of these Orc-characteristic domains [ 11 ].…”

Phosphoryl transfer reaction catalyzed by membrane diacylglycerol kinase: a theoretical mechanism study

“…DgkA uniquely has a very short sequence (only 121 residues) 2,3 that contains none of the conventional kinase sequence motifs, 4,5 such as P-loops and Walker motifs for ATP binding. 4,6 Despite its simplicity, DgkA appears to be an evolutionarily optimized enzyme in the sense that its biochemical reaction rate is substrate diffusion-controlled. 7 Furthermore, DgkA has high nucleotide substrate specificity for ATP.…”