CHAPTER 24 – Evolution of Protein Molecules

Inference of macromolecular assemblies from crystalline state.

On the Nature of Allosteric Transitions: A Plausible Model

Solvent content of protein crystals.

Stanford Moore, William Stein, and Anfinsen were awarded the Nobel Prize in Chemistry in 1972 for \"their contribution\n to the understanding of the connection between chemical structure and catalytic activity of the active center of the ribonuclease\n molecule.\" In his Nobel Lecture, Anfinsen provided a sketch of the rich history of research that provided the foundation\n for his work on protein folding and the \"Thermodynamic Hypothesis,\" and outlined potential avenues of current and\n future scientific exploration.

https://web.iitd.ac.in/~amittal/1973_Anfinsen_Science.pdf

Principles that Govern the Folding of Protein Chains

Allosteric mechanism of haemoglobin: rupture of salt-bridges raises the oxygen affinity of the T-structure.

Electron Spin Resonance in Myoglobin and Haemoglobin:
Orientation of the Four Haem Groups in Haemoglobin

Electron Spin Resonance in Myoglobin and Hæmoglobin: Orientation of the Four Hæm Groups in Hæmoglobin

2-[4-(3,4-Dichlorophenylureido)phenoxy]-2-methylpropionic acid, LR16, combines with two symmetrically related sites in the central cavity of deoxyhemoglobin, 20 A away from the binding site of 2,3-bisphosphoglycerate, and acts as an allosteric effector synergistic with 2,3-bisphosphoglycerate. LR16 (1 mM) raises P50, the partial pressure of oxygen needed to achieve half-saturation with oxygen of a hemolysate of human hemoglobin, about 50 times more strongly than 1 mM 2,3-bisphosphoglycerate. Oral administration of LR16 (at small doses that produced no ill effects) to rats that were fed a diet rich in cholesterol caused substantial reductions of total serum cholesterol and low density lipoprotein-cholesterol, while high density lipoprotein-cholesterol remained unchanged.

LR16, a compound with potent effects on the oxygen affinity of hemoglobin, on blood cholesterol, and on low density lipoprotein.

Horse methaemoglobin crystallizes with two molecules in a face-centred monoclinic unit cell (space group C 2), in which rigid layers of molecules parallel to (001) alternate with layers of liquid. The crystals can be made to swell and shrink in a series of steps involving changes in d (001) and in the angle β. It appears that only the distances between the molecular layers change, but not their internal structure. The lattice changes allow the modulus of the molecular Fourier transform to be sampled along lines of constant h and k. When k = 0 the transform is real and the sampled values of | F | describe a series of loops and nodes. Part I of this series dealt with the principles of deciphering these and established the absolute signs of the 00 l reflexions. In part II the absolute signs of certain 20 l reflexions were derived from the changes in intensity produced by the substitution of salt solution for water as the liquid of crystallization. In this paper the transform is measured for all values of h and l up to λ/ d = 0·24, comprising nine layer lines in all. The absolute signs of layer lines with h > 2 are left in doubt, but many sign relations are established within each of them. It is difficult to assess exactly the number of sign relations found by the transform method, but it is estimated that the number of alternative sign combinations is reduced from 296 to 218. The remaining uncertain ties are cleared up by the isomorphous replacement method described in part IV .

/pdf/the-structure-of-haemoglobin-iii-direct-determination-of-the-8livniu8q6.pdf

Max F. Perutz

Papers

Allosteric mechanism of haemoglobin: rupture of salt-bridges raises the oxygen affinity of the T-structure.

Electron Spin Resonance in Myoglobin and Hæmoglobin: Orientation of the Four Hæm Groups in Hæmoglobin

LR16, a compound with potent effects on the oxygen affinity of hemoglobin, on blood cholesterol, and on low density lipoprotein.

The Structure of Haemoglobin. III. Direct Determination of the Molecular Transform

Structure and function of haemoglobin philly (Tyr C1 (35) β→Phe)