An ATP, adenosine triphosphate, binding motif is a short sequence within an ATP binding protein’s primary structure. The binding motif is associated with a protein’s structure and/or function. ATP is a molecule of energy, and can be a coenzyme, involved in a number of biological reactions. ATP is proficient at interacting with other molecules through a binding site. The ATP binding site is the environment in which ATP catalytically actives the enzyme and, as a result, is hydrolyzed to ADP. The short motifs involving ATP-binding are the Walker A, also known as the P-loop, Walker B, ABC signature, and switch motif. The binding of ATP causes a conformational change to the enzyme it is interacting with. These conformational changes have been observed through X-ray crystallography.
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The same ATP binding motif is used in many proteins: hence a "motif" that is similar across a range of proteins. The genetic and functional similarity of such a motif demonstrates micro-evolution: proteins have co-opted the same binding sequence from other enzymes rather than developing them independently.
ATP binding sites, which may be representative of an ATP binding motif, are utilized on many proteins which perform function requiring an input of energy (from ATP). Such sites are located on active membrane transporters, microtubule subunits, flagellum proteins, and various hydrolytic and proteolytic enzymes.
Structure
All of the ATP binding domains are made up of an estimated 250 residues. These residues are folded into six α-helices and five β-strands. The Walker site A has a primary sequence of GXXGXFKS(or T), in which X can represent any amino acid. The Walker B site has a primary sequence of hhhhD, in which h represents any hydrophobic amino acid. Due to the variety of different amino acids that can be used in the primary sequence, of both the Walker site A and B, these sequences are highly conserved when it comes to the non-variant amino acids within the sequence. A mutation of any of the highly conserved amino acids may affect the binding ATP or could interfere with the catalytic activity of the enzyme.
A primary amino acid sequence determines the structure of each motif. Structurally, the Walker A motif consists of an α-helix and is always followed by a glycine-rich loop. The Walker B motif is a β-strand and a highly conserved sequence, named the linker peptide LSGGQQ(or R or K)QR, directly follows the motif. The Walker motifs are connected to each other by a peptide sequence of about 100 residues. Structurally, these connecting residues fold into an α-helical domain. The switch motif has been found to be located at the end of the β4-strand in ATP binding proteins.
Function
Each ATP binding motif has a different role to play whether it is directly involved with the binding of ATP or helping with the construction of the ATP-binding cassette transporter. Inside the Walker A binding motif a lysine side chain can be found, which is essential for the binding of two phosphates (L and Q) along with the binding of a nucleotide. In order for the Walker A motif to bind to the nucleotide, the ABC signature motif signals the nucleotide when the ATP molecule has bound to the ATP binding site. The glycine-rich loop that proceeds the Walker A motif has shown that the mutation of the third or fourth glycine amino acid has resulted in the loss of enzymatic activity and compromised the binding of ATP. The Walker B motif contains the amino acid glutamate within the short sequence. Glutamate can be used to perform a nucleophilic attack on the ATP molecule. Found in the switch binding motif is a histidine residue. The function of the histidine is to influence the reaction catalytically.