Kendrew models

C3, C6 and C5 axial positions and at C2, C3 and C6 equatorial positions strongly reduce the reaction rate due to steric interactions with active site residues or the nicotinamide ring of NAD. These findings were determined by correlation of reaction rate studies with model-building using Kendrew models. 

This last step, i.e. the one in which the model is rebuilt to have correct geometry, is the first step in this sequence in which the power of the maxi computer is essential. The result of this procedure is a model equivalent to one constructed in a Richards box of rigid brass parts (Kendrew models). The brass model is varied by internal rotation about the connections between the parts. Of course the computed model can be altered also by internal rotation about the bonds connecting the rigid parts. But by using the computational power of the maxi computer, the computed model can be adjusted in another convenient manner which can not be implemented when working with a brass model. 

The crystals obtained by Kartha et al. contain two nonequivalent molecules and hence six nonequivalent proline residues. The authors report average geometric parameters describing these six residues plus two more residues in crystals of a cyclic tripeptide containing two prolines and one hydroxyproline. We built a Kendrew model with approximately this geometry and measured its coordinates with a ruler in order to get a starting set of coordinates for our minimization programs. 

Reference to Figure 2 indicates some of the other important residues in the neighborhood of the two active aspartic acid side chains. It is clear that Asp-32 and Asp-215 are in very close contact (preliminary measurements from the Kendrew model indicate that the two carboxyl groups are approximately coplanar and about 2.6 A separates two of the oxygen atoms). The pH profiles of k or pepsin-catalyzed hydrolysis of small synthetic... 

The proposed mechanism of acid protease catalysis is illustrated in Figure 8 in which the bond cleavage step is shown. The scissile peptide bond of a hypothetical substrate RCO-NHR is included, but detailed enzyme-substrate side chain interactions have been omitted for clarity. We have confirmed via model building experiments on the Kendrew model of penicillopepsin that substrates such as L-Phe-L-Phe can be accommodated as shown in Figure 8 and that the substrate s side chains interact with hydrophobic pockets in the proximity of the active site. 

Figure 2-121. The first brass-wire model of a macromolecule built by Kendrew et al. in 1958 [193],...

Figure 2.1 Kendrew s model of the low-resolution structure of myoglobin shown in three different views. The sausage-shaped regions represent a helices, which are arranged in a seemingly Irregular manner to form a compact globular molecule. (Courtesy of J.C. Kendrew.)...

Kendrew, J.C., et al. A three-dimensional model of the myoglobin molecule obtained by x-ray analysis. Nature 181 662-666, 1958. 

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. 

John Kendrew found that the x-ray diffraction pattern of crystalline myoglobin (isolated from muscles of the sperm whale) is very complex, with nearly 25,000 reflections. Computer analysis of these reflections took place in stages. The resolution improved at each stage, until in 1959 the positions of virtually all the non-hydrogen atoms in the protein had been determined. The amino acid sequence of the protein, obtained by chemical analysis, was consistent with the molecular model. The structures of thousands of proteins, many of them much more complex than myoglobin, have since been determined to a similar level of resolution. 

There are many other discussions of model structures. Pertinent reviews are those of Bragg, Kendrew, and Perutz (262), Robinson and Ambrose (1733), Donohue (536), and Pauling and Corey (1591a). Mizushima (1856) suggests a general mathematical approach to helical structures. 

FIGURE 10.15 A model of yeast phenylalanine tRNA built according to an electron density map computed using 2.8 A resolution X-ray data. The model is constructed of Kendrew parts connected together by tiny screws. It required several months to build and is roughly 6 feet by 4 feet by 3 feet in size. It was constructed at MIT in 1972 by the author. 

Kendrew, J. C., t3odcj. G., Dintzis, H. M., Parrish, R. G.. Wyckoff. H.. and Pliiilips, D. C. 1958. A three-dimensional model of the iTiyoglQbin molecule obtained by x-ray analysis. Nuture... 

The solution to any problem with a stereochemical aspect requires access to molecular models. Of these, there are two main kinds. The first is the skeletal or framework model such as those devised by Dreiding or Kendrew. These indicate the centres of bonds that join atoms, and are useful to find conformations suitable for interaction between two molecules. The other type of model, space-filling (e.g. CPK, or Courtauld), shows both the shape of the molecule and the volume that it occupies. This kind is very useful for showing the overall shape, surface and volume of a molecule. With practice, a chemist can learn to see a conformational drawing as a three-dimensional skeletal shape, and eventually as a space-filling molecule. There are also the CCS models, which are fundamentally skeletal models that can be quickly converted to space-filling types and back again (Clarke, 1977). 

---