Perutz model

A model for the allosteric behavior of hemoglobin is based on recent observations that oxygen is accessible only to the heme groups of the a-chains when hemoglobin is in the T conformational state. Perutz has pointed out that the heme environment of /3-chains in the T state is virtually inaccessible because of steric hindrance by amino acid residues in the E helix. This hindrance dis-... 

Hemoglobin Is a large complex protein molecule the atomic model of oxyhemoglobin at 2.8 a resolution has been reported In 1968 by Perutz and coworkers, and a similar model of deoxy-hemoglobin In 1970 (1,2). The molecule Is a spheroid, approx-... 

Protein structures are so diverse that it is sometimes difficult to assign them unambiguously to particular structural classes. Such borderline cases are, in fact, useful in that they mandate precise definition of the structural classes. In the present context, several proteins have been called //-helical although, in a strict sense, they do not fit the definitions of //-helices or //-solenoids. For example, Perutz et al. (2002) proposed a water-filled nanotube model for amyloid fibrils formed as polymers of the Asp2Glni5Lys2 peptide. This model has been called //-helical (Kishimoto et al., 2004 Merlino et al., 2006), but it differs from known //-helices in that (i) it has circular coils formed by uniform deformation of the peptide //-conformation with no turns or linear //-strands, as are usually observed in //-solenoids and (ii) it envisages a tubular structure with a water-filled axial lumen instead of the water-excluding core with tightly packed side chains that is characteristic of //-solenoids. 

It has been suggested that the Sup35p filament may be a bundle of four cylindrical //-sheets or nanotubes (Kishimoto et al., 2004). The nanotube is a hypothetical structure (Perutz et al, 2002) whose winding of the polypeptide chain is topologically similar to that of a //-helix but it is round in cross section and water filled whereas //-helices have cross sections with triangular or other shapes and water is largely excluded from their interiors (Kajava and Steven, 2006). The model of Kishimoto et al. envisaged six coils... 

While a polar-zipper model was initially proposed for Asp2Glni3Lys2 (Perutz et ah, 1994), more recently a water-filled nanotube was proposed in which the homopolymer in the / -conformation forms a helical array having 20 residues per turn (Perutz et ah, 2002a,b). (In the earlier work, the diffraction pattern had been interpreted as a fiber pattern—that is, with the 4.8-A reflection in the fibril direction.) Rather than being attributed to intersheet stacking, the 8.4-A reflection was not accounted for. Further,... 

Fig. 14. Cylindrical /1-helix model of polyglutamine fibrils, from Perutz et at. (2002a).

Haemoglobin is one of the most well studied and best understood proteins thanks largely to the early work of Max Perutz, John Kendrew and colleagues. Haemoglobin is now often used as a model allosteric protein and to illustrate the impact of protein structural alterations in disease. 

Although neither structure has yet been solved at atomic resolution Perutz has recentty built an atomic model of horse oxyhaemoglobin 41). This model is based on the Fourier sjmthesis of horse oxyhaemoglobin at 5.5 A resolution, the Fourier synthesis of myoglobin at atomic resolution,... 

Perutz and coworkers [180] have used 2D EXSY to study the dynamic behavior of RhCp(PMe3)(q -naphthalene), 109, which is thought to be a model intermediate for the oxidative addition of arenes to a metal center. In this complex, there are two processes taking place. The first involves an equilibrium between the -naphthalene complex, 109, and the naphthyl hydride complex, 110. The second process involves an intramolecular [l,3]-shift which moves the coordination site of the naphthalene ring from one side of the ring to the other (Scheme 1.12). 

Fiqure 10.2 Balsa wood models of oxy- and deoxyhemoglobin. The hemes are represented by disks. Note the increased separation of the f3 subunits on deoxygenation. This is a historic photograph from the heroic early days of x-ray crystallography. [Courtesy of Dr. M. F. Perutz.]... 

Perutz has presented the most comprehensive allosteric model for the function of hemoglobin. It is of the symmetrical type and is presented in Figure 7.8. This model provides for the binding of 2,3-DPG by the T forms but not by the R... 

Molecular graphics of molecular models and MD trajectories. Available via anonymous ftp from perutz.scripps.edu (137.131.152.27). Sun, DEC, and Stardent. 

Perutz s hypothesis (55) and the MWC model (56) for allostery, that the more tension is added to the tense (deoxy) state of Hb, the greater the shift to the right of the oxygen-... 

The observation by Mac Arthur (1943) and Perutz (1951) of a meridional reflection in a-keratin of spacing 1.5 A equal to the axial translation per residue in the a-helix provided considerable support for this model but, as noted by Pauling and Corey, the strong meridional arc of spacing 5.15 A was not accounted for without further assumptions. 

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