Perutz

For their work on myoglobin and hemoglobin respec tively John C Kendrew and Max F Perutz were awarded the 1962 Nobel Prize in chemistry... 

Perutz, M. Protein Structure New Approaches to Disease and Therapy. New York Freeman, 1992. 

Perutz, M.F. New x-ray evidence on the configuration of polypeptide chains. Polypeptide chains in poly-g-benzyl-t-glutamate, keratin and haemoglobin. Nature 167 1053-1054, 1951. 

Perutz, M.F., et al. Structure of haemoglobin. A three-dimensional Fourier synthesis at 5.5 A resolution, obtained by x-ray analysis. Nature 185 416-422, 1960. 

Figure 3.13 The hemoglobin molecule is built up of four polypeptide chains two a chains and two (3 chains. Compare this with Figure 1.1 and note that for purposes of clarity parts of the a chains are not shown here. Each chain has a three-dimensional structure similar to that of myoglobin the globin fold. In sicklecell hemoglobin Glu 6 in the (3 chain is mutated to Val, thereby creating a hydrophobic patch on the surface of the molecule. The structure of hemoglobin was determined in 1968 to 2.8 A resolution in the laboratory of Max Perutz at the MRC Laboratory of Molecular Biology, Cambridge, UK.

In viw PAI and antithrombin are stabilized in their active forms by binding to vitronectin and heparin, respectively. These two serpins seem to have evolved what Max Perutz has called "a spring-loaded safety catch" mechanism that makes them revert to their latent, stable, inactive form unless the catch is kept in a loaded position by another molecule. Only when the safety catch is in the loaded position is the flexible loop of these serpins exposed and ready for action otherwise it snaps back and is buried inside the protein. This remarkable biological control mechanism is achieved by the flexibility that is inherent in protein structures. 

Perutz, M. Mechanisms of cooperativity and allosteric regulation in proteins. Cambridge Cambridge University Press, 1990. 

In small-molecule crystallography the phase problem was solved by so-called direct methods (recognized by the award of a Nobel Prize in chemistry to Jerome Karle, US Naval Research Laboratory, Washington, DC, and Herbert Hauptman, the Medical Foundation, Buffalo). For larger molecules, protein aystallographers have stayed at the laboratory bench using a method pioneered by Max Perutz and John Kendrew and their co-workers to circumvent the phase problem. This method, called multiple isomorphous replacement... 

As noted, hemoglobin is an tetramer. Each of the four subunits has a conformation virtually identical to that of myoglobin. Two different types of subunits, a and /3, are necessary to achieve cooperative Oa-binding by Hb. The /3-chain at 146 amino acid residues is shorter than the myoglobin chain (153 residues), mainly because its final helical segment (the H helix) is shorter. The a-chain (141 residues) also has a shortened H helix and lacks the D helix as well (Figure 15.28). Max Perutz, who has devoted his life to elucidating the atomic structure of Hb, noted very early in his studies that the molecule was... 

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-... 

J. C. Kendrew and M. F. Perutz (Cambridge) the structures of globular proteins. 

M. F. Perutz, Proteins and Nucleic Acids, Elsevier, Amsterdam (1962). 

Aspects of organotransition metal photochemistry and their biological significance. E. A. Koerner von Gustorf. L. H. G. Leenders, I. Fischler and R. N. PerutZ, Adv. Inorg. Chem. Radiochem., 1976,19, 65-183 (632). 

Photochemical reactions involving matrix-isolated atoms. R. N. Perutz, Chem. Rev., 1985, 85, 77 (187). 

Perutz MF, Lehmann J. Molecular pathology of human haemoglobin. Nature 1968 219 902-9. 

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-... 

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