P-loop structure

Figure S.28 Schematic diagrams of the two-sheet P helix. Three complete coils of the helix are shown in (a). The two parallel P sheets ate colored gieen and red, the loop regions that connect the P strands ate yellow, (b) Each stmctuial unit Is composed of 18 residues forming a P-loop-P-loop structure. Each loop region contains six residues of sequence Gly-Gly-X-Gly-X-Asp where X is any residue. Calcium Ions are bound to both loop regions. (Adapted from F. Jumak et al., Ciirr. Opin. Struct. Biol. 4 802-806, 1994.)...

The P-loop structure in crystals of Dictyostelium myosin II is shown in Fig. 5 (Smith and Rayment, 1996). This structure provides an environment where MgATP is coordinated with a large number of the surrounding amino acid side groups. For example, the Mg2+ ion, in addition to interacting with the two terminal phosphates of ATP, is coordinated directly to... 

NMP Kinases Are a Family of Enzymes Containing P-Loop Structures... 

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. 

Each repeat forms a right-handed P-loop-a structure similar to those found in the two other classes of a/p structures described earlier. Sequential p-loop-a repeats are joined together in a similar way to those in the a/P-bar-rel stmctures. The P strands form a parallel p sheet, and all the a helices are on one side of the P sheet. However, the P strands do not form a closed barrel instead they form a curved open stmcture that resembles a horseshoe with a helices on the outside and a p sheet forming the inside wall of the horseshoe (Figure 4.11). One side of the P sheet faces the a helices and participates in a hydrophobic core between the a helices and the P sheet the other side of the P sheet is exposed to solvent, a characteristic other a/p structures do not have. 

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.

In almost every one of the more than 100 different known a/p structures 1 of this class the active site is at the carboxy edge of the p sheet. Functional residues are provided by the loop regions that connect the carboxy end of the strands with the amino end of the a helices. In this one respect a fun-I damental similarity therefore exists between the a/p-barrel structures and the I open a/p-sheet structures. 

The a/p-barrel structure is one of the largest and most regular of all domain structures, comprising about 250 amino acids. It has so far been found in more than 20 different proteins, with completely different amino acid sequences and different functions. They are all enzymes that are modeled on this common scaffold of eight parallel p strands surrounded by eight a helices. They all have their active sites in very similar positions, at the bottom of a funnel-shaped pocket created by the loops that connect the carboxy end of the p strands with the amino end of the a helices. The specific enzymatic activity is, in each case, determined by the lengths and amino acid sequences of these loop regions which do not contribute to the stability of the fold. 

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. 

In these p-helix structures the polypeptide chain is coiled into a wide helix, formed by p strands separated by loop regions. In the simplest form, the two-sheet p helix, each turn of the helix comprises two p strands and two loop regions (Figure 5.28). This structural unit is repeated three times in extracellular bacterial proteinases to form a right-handed coiled structure which comprises two adjacent three-stranded parallel p sheets with a hydrophobic core in between. 

The basic structural unit of these two-sheet p helix structures contains 18 amino acids, three in each p strand and six in each loop. A specific amino acid sequence pattern identifies this unit namely a double repeat of a nine-residue consensus sequence Gly-Gly-X-Gly-X-Asp-X-U-X where X is any amino acid and U is large, hydrophobic and frequently leucine. The first six residues form the loop and the last three form a p strand with the side chain of U involved in the hydrophobic packing of the two p sheets. The loops are stabilized by calcium ions which bind to the Asp residue (Figure S.28). This sequence pattern can be used to search for possible two-sheet p structures in databases of amino acid sequences of proteins of unknown structure. 

In both structures the ion is coordinated to six ligands with octahedral geometry. Four water molecules as well as the side chain oxygen atom of a serine residue from the P-loop and one oxygen atom from the (3-phosphate bind to Mg + in the GDP structure. Two of the water molecules are replaced in the GTP structure by a threonine residue from switch I and an oxygen atom from the y phosphate (similar to the arrangement shown in... 

The lattice of implications among (1) - (8) and strong equivalence appears below. No implications shown can be reversed and no implications not in the diagram hold. Conditions (7) and (8) represent an attempt to formalize the idea of preserving loop structure, since cycles in P correspond to cycles in P and cycles in P, if repeated often enough, correspond to cycles in P. ... 

The transformation is global. The schemes P and P are strongly computationally equivalent in the restricted sense - if we omit from the test added computational histories of (P,I, a) and (P, I, a) all values of the new variables and all tests involving these variables (i.e. test Z ) for an interpretation I extending I to all of P and P, then the resulting lists are equal. However the loop structure of P has been drastically changed and there is no simple relationship between the graphs of P and P. ... 

Fig. 4.12(a). An outline structure of a protein (here the enzyme phospholipase A2), showing a-helical runs of amino acids as cylinders (A-E) and anti-parallel P-sheet runs as heavy black arrows. Disulfide cross-links are shown (the enzyme is extracellular), and runs of no a/p secondary structure appear as thin lines. The structure is relatively immobile, and binds calcium in a constrained loop. (Reproduced with permission from Professor J. Drenth.)... 

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