Greek key helix bundles

Domain 1 Greek key helix bundle Domain 2 miscellaneous antiparallel a Dehydrogenases, see Alcohol, Glyceraldehyde phosphate, Malate, or Lactate... 

Either up-and-down or Greek key helix bundle Pyruvate kinase (Stuart et ah, 1979)... 

FlC. 89. Hemoglobin (fi subunit) as an example of a Greek key helix bundle, (a) a-Carbon stereo (b) schematic drawing of the backbone as two perpendicular layers of a-helices (shown here as cylinders) (c) schematic drawing of the backbone as a Greek key helix bundle (from the same viewpoint as in a) (d) schematic end-on view of the hemoglobin helix bundle, to show that it is a slightly flattened cylinder in cross section (die C-D loop is shown dashed because it would cover part of the cylinder). 

These four structures then form the second major subgrouping of antiparallel a domains, which we will call Greek key helix bundles (see Fig. 73). The helix elements lie on an approximate cylinder (see Fig. 89d for an end view), with 0 to 45° right-handed twist relative to the cylinder axis they are connected with a Greek key topology which can have either a counterclockwise (globins) or a clockwise (thermolysin d2 and T4 lysozyme d2) swirl when viewed from the outside. 

The connectivity is not known for the seven-helix bundle of purple membrane protein (Henderson and Unwin, 1975), but on the basis of its resemblance to other antiparallel a proteins the most likely topologies would be either up-and-down or Greek key (see below). An analysis based on the sequence and the relative electron-densities of the helices (Engelman et ah, 1980) considers a left-handed up-and-down topology as the most probable model. 

Fig. 105. Examples of small disulfide-rich or metal-rich proteins (shown on the right side) compared with their more regular counterparts in other structural categories (shown at the left), (a) Tobacco mosaic virus protein, an up-and-down helix bundle (b) cytochrome bs, a distorted up-and-down helix bundle (c) trypsin domain 1, a Greek key antiparallel /3 barrel (d) high-potential iron protein, a distorted Greek key /3 barrel (e) glutathione reductase domain 3, an open-face sandwich fi sheet (f) ferredoxin, a distorted open-face sandwich f) sheet.

The overall three-dimensional structure of a protein is called the tertiary structure. The tertiary structure represents the spatial packing of secondary structures (Ofran and Rost, 2005). As for secondary structures, there are several different classes of tertiary structures. More advanced classification schemes take into account common topologies, motifs, or folds (Wishart, 2005). Common tertiary folds include the a/p-barrel, the four-helix bundle, and the Greek key (we will discuss protein folding further in Chapter 14). Any change to any part of the structure of a protein will have an impact on its biological activity (Thomas, 2003). 

FIGURE 12.36. Various types of protein tertiary structure, (a) An antiparallel a structure (cytochrome 6502) an up-and-down helix bundle (Ref. 113), (b) an antiparallel / structure (Cu,Zn superoxide dismutase) a Greek key (3 barrel (Ref. 114), and (c) and a parallel aj structure (triose phosphate isomerase) a singly wound parallel 0 barrel (Ref. 115). (Courtesy Jane S. Richardson)... 

A description of the protein-structure hierarchy is incomplete without a discussion of structural motifs, which are critical to an understanding of protein structure [17]. Identification of recurring motifs in protein structures has refined our knowledge of the protein-structure hierarchy these motifs occur at all levels from primary to tertiary. The Phe-Asp-Thr-Gly-Ser sequence found in the active site of all aspartic acid proteinases, and the Gly-Gly-X-Leu sequence (where X represents any amino acid residue) that predicts a 3-strand for the last two residues [17], are examples of sequence motifs a-helices, P-strands, and turns are examples of secondary-structural motifs PaP and PxP units, P-hairpins, and Greek keys are examples of supersecondary-structural motifs and four-a-helix bundles and TIM barrels are examples of tertiary-structural motifs. The tertiary fold of a protein is characterized by its tertiary-structural motif. 

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