P-loop motif

The characteristic (consensus) sequence ofP-loops (the Walker A motif Walker et al., 1982) is Gly-x-x-x-x-Gly-Lys-Thr/Ser (the region in red in Fig. 5) this sequence is often used in bioinformatic searches to identify proteins related to this family. Each myosin and kinesin has a single P-loop. For example, Dictyostelium myosin II has the sequence as in Fig. 5 (179) G-E-S-G-A-G-K-T (186). On the other hand, dynein, with a heavy chain that partly forms a ringlike core complex of six AAA+ domains, has P-loop motifs in the first four of these domains (e.g., G-P-A-G-P-G-K-T). There may be a complex series of interactions between these various sites to generate movement, but the P-loop in the third domain has been shown to be essential for dynein motor function (Silvanovich et al., 2003). 

Homology alignment studies revealed that LdAdK has only about 40 and 31% identity with human and T. gondii enzymes respectively (Fig. 3A). However, despite this limited identity, LdAdK possesses all the characteristics typical of AdK from all known sources. First, similar to that of other AdKs, LdAdK lacks the consensus P-loop motif and secondly, LdAdK harbors two amino acid sequence motifs that are distinctive of the PfkB family of carbohydrate... 

Sinha KM, Ghosh M, Das I et al. Molecular cloning and expression of adenosine kinase fi-om Leishmania donovani Identification of unconventional P-loop motif. Biochem J 1999 339(Pt 3) 667-673. 

Figure 2.21 illustrates the 24 possible ways in which two adjacent p hairpin motifs, each consisting of two antiparallel p strands connected by a loop region, can be combined to make a more complex motif. 

Polypeptide chains are folded into one or several discrete units, domains, which are the fundamental functional and three-dimensional structural units. The cores of domains are built up from combinations of small motifs of secondary structure, such as a-loop-a, P-loop-p, or p-a-p motifs. Domains are classified into three main structural groups a structures, where the core is built up exclusively from a helices p structures, which comprise antiparallel p sheets and a/p structures, where combinations of p-a-P motifs form a predominantly parallel p sheet surrounded by a helices. 

Figure 4.11 Schematic diagram of the structure of the ribonuclease inhibitor. The molecule, which is built up by repetitive P-loop-a motifs, resembles a horseshoe with a 17-stranded parallel p sheet on the inside and 16 a helices on the outside. The P sheet is light red, a helices are blue, and loops that are part of the p-loop-(x motifs are orange. (Adapted from B. Kobe et al.. Nature 366 7S1-756,...

Figure 4.12 Schematic diagram illustrating the role of the conserved leucine residues (green) in the leucine-rich motif in stabilizing the P-loop-(x structural module. In the ribonuclease inhibitor, leucine residues 2, 5, and 7 from the P strand pack against leucine residues 17, 20, and 24 from the a helix as well as leucine residue 12 from the loop to form a hydrophobic core between the P strand and the a helix.

The horseshoe structure is formed by homologous repeats of leucine-rich motifs, each of which forms a p-loop-a unit. The units are linked together such that the p strands form an open curved p sheet, like a horseshoe, with the a helices on the outside of the p sheet and the inside exposed to solvent. The invariant leucine residues of these motifs form the major part of the hydrophobic region between the a helices and the p sheet. 

Figure 6.3. Alignments of regions identified to be important in nickel accessory proteins for maturation of the final nickel sink, the nickel-containing enzyme. A, The His-rich regions of known or putative HypB proteins and the UreE and CooJ proteins from various organisms. Reprinted with permission from Olson and Maier (2000). B, Alignment of the G motifs from known or putative HypB proteins and the related nucleotide-binding P-loop residues (in the G1 region) of CooC and UreG. (Adapted from Olson and Maier (2000).

The catalytic center of the protein tyrosine phosphatases includes ca. 230 amino acids and contains the conserved sequence motif HA -C-(X)5-R-S/T-G/A/P (X is any amino acid) which is involved in phosphate binding and in catalysis and is part of a loop known as the P loop. The available structural data on the catalytic domains of protein tyrosine phosphatases indicate that the mechanism shown schematically in Fig. 8.17 is likely (see Tainer and Russell, 1994). The invariant Cys and Arg residues of the P loop have a central function in binding and cleavage of the phosphate residue. 

Of the two, classic ones are far less common however, those that do exist are frequently found at the loop end of 3-hairpinsJ81 Inverse y-tums generally do not lead to peptide chain reversal and are frequently situated at either the end of a-helices or within strands of p-sheets or adjacent to certain loop motifs. 91 They are generally well conserved during evolution and some are found at key positions within proteins. 

The physical basis of the kinetic linkage between GTP hydrolysis and conformational change arises from the involvement of Switch I and Switch II in both processes. The P-loop, or Walker A motif (Walker et at, 1982)... 

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