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.

Keywords: P‐loop; nucleotide‐binding; protein fold; sequence motif; adenone‐5′‐triphosphate

Figure 1.

Crystal structure of yeast adenylate kinase (pale green) bound to the bi‐substrate inhibitor bis(adenosine)‐5′‐pentaphosphate (Ap5A) and Mg2+ at 1.96 Å resolution (PDB 1AKY). The β‐strand‐loop‐α‐helix motif containing the P‐loop is coloured light blue, with the catalytic Lys16 coloured blue, and the three Gly residues of the P‐loop coloured yellow. Hydrogen‐bonding interactions with the Ap5A inhibitor (red=oxygen, blue=nitrogen, grey=carbon and green=phosphorous) are indicated as grey dashed lines. This figure was prepared using PyMol 1.0r2 (http://www.pymol.org).

Figure 2.

Crystal structure of biotin carboxylase (pale green) from Staphylococcus aureus (PDB 2VPQ), highlighting interactions between ATP with proteins belonging to the ATP‐grasp fold. The ATP‐grasp fold consists of a α/β/α unit, including a pair of antiparallel β‐strands connected by a loop. This loop (light blue) contains a conserved Gly (Gly161) that forms a hydrogen bond with the β‐phosphoryl moiety. Additionally, sequence‐conserved hydrogen‐bonding interactions involve a polar residue (Glu199) with the N6 atom of the adenine base, as well as a pair of Lys residues (Lys115, Lys157) with the α‐ and β‐phosphoryl moietieis of ATP. This figure was prepared using PyMol 1.0r2 (http://www.pymol.org/).

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Matte, Allan, and Delbaere, Louis TJ(Apr 2010) ATP‐binding Motifs. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0003050.pub2]