ATP/GTP-binding site motif A (P-loop)

From sequence comparisons and crystallographic data analysis it has been shown [1,2,3,4,5,6] that an appreciable proportion of proteins that bind ATP or GTP share a number of more or less conserved sequence motifs. The best conserved of these motifs is a glycine-rich region, which typically forms a flexible loop between a β-strand and an α-helix. This loop interacts with one of the phosphate groups of the nucleotide. This sequence motif is generally referred to as the 'A' consensus sequence [1] or the 'P-loop' [5].

There are numerous ATP- or GTP-binding proteins in which the P-loop is found. We list below a number of protein families for which the relevance of the presence of such motif has been noted:

• ATP synthase α and β subunits (see <PDOC00137>).
• Myosin heavy chains.
• Kinesin heavy chains and kinesin-like proteins (see <PDOC00343>).
• Dynamins and dynamin-like proteins (see <PDOC00362>).
• Guanylate kinase (see <PDOC00670>).
• Thymidine kinase (see <PDOC00524>).
• Thymidylate kinase (see <PDOC01034>).
• Shikimate kinase (see <PDOC00868>).
• Nitrogenase iron protein family (nifH/chlL) (see <PDOC00580>).
• ATP-binding proteins involved in 'active transport' (ABC transporters) [7] (see <PDOC00185>).
• DNA and RNA helicases [8,9,10].
• GTP-binding elongation factors (EF-Tu, EF-1α, EF-G, EF-2, etc.).
• Ras family of GTP-binding proteins (Ras, Rho, Rab, Ral, Ypt1, SEC4, etc.).
• Nuclear protein ran (see <PDOC00859>).
• ADP-ribosylation factors family (see <PDOC00781>).
• Bacterial dnaA protein (see <PDOC00771>).
• Bacterial recA protein (see <PDOC00131>).
• Bacterial recF protein (see <PDOC00539>).
• Guanine nucleotide-binding proteins α subunits (Gi, Gs, Gt, G0, etc.).
• DNA mismatch repair proteins mutS family (See <PDOC00388>).
• Bacterial type II secretion system protein E (see <PDOC00567>).

Not all ATP- or GTP-binding proteins are picked-up by this motif. A number of proteins escape detection because the structure of their ATP-binding site is completely different from that of the P-loop. Examples of such proteins are the E1-E2 ATPases or the glycolytic kinases. In other ATP- or GTP-binding proteins the flexible loop exists in a slightly different form; this is the case for tubulins or protein kinases. A special mention must be reserved for adenylate kinase, in which there is a single deviation from the P-loop pattern: in the last position Gly is found instead of Ser or Thr.