Overall Fold

Figure 6.12 (a) The overall fold of the rubrerythrin subunit. Helical regions are in yellow, 6-sheet... 

Proteins can be classed into groups based on their overall 3-D shapes, known as protein folds (O Figure 22-la). In general, proteins that have similar functions have similar folds. This means that if you are the proud parent of an unknown protein whose structure is solved, it may be possible to make educated guesses as to the function of the protein based on its overall fold. There are a number of well-known exceptions to this [notably, the serine protease family, subtilisin and trypsin/chymotrypsin (Hartley, 1979)], but the... 

The solution structure of Aspl3Cys, a thermostable mutant of Fd, has been solved by H-NMR and compared to that of the wild-type (WT) protein. The overall folding of the WT protein was maintained in the mutant, except for the immediate vicinity of the new cysteine. The geometry of the new cluster was a typical 4Fe-4S cubane, as monitored by the hyperfine shifts of the co-ordinated cysteines. Conformational heterogeneity, which was partly abolished by heat treatment, was observed and ascribed to a kinetic phenomenon. 

Fig. 2. Molecular model of the eNOS heme domain dimer. Each monomer consists of residues 69-482. The pterin is depicted as a space-filled model and the hemes are the white stick models. The single Zn ion situated at the lower part of the dimer interface is depicted as the white ball. The overall fold is unique to NOS.

II aldolases FucA and RhuA from E. coli have been crystallized solution of their spatial structures confirmed a close similarity in their overall fold [14]. Both enzymes are homotetramers in which subunits are arranged in C4 symmetry. The active site is assembled in deep clefts at the interface between adjacent subunits, and the catalytic zinc ion is tightly coordinated by three His residues. From X-ray... 

The procedure of crystallography is concerned with the determination of the overall shape of the molecule by a low resolution study. Then the structure is refined to produce a high resolution structure. How far this refinement procedure can proceed is not certain. It is important to discover to what extent the solution structure resembles the X-ray structure. This comparison can be done at two levels, that of the overall fold and that of the high resolution structure. At the highest resolution it is... 

There is good evidence in a number of systems that the overall folding of a globular protein (the outline structure) is in fact very similar in the... 

The overall fold of a globular protein molecule in solution is likely to be given by the X-ray structure of the molecule in a crystal. This has been shown to be the case in detail for one protein, lysozyme, by means of nuclear magnetic resonance techniques, and is highly probable for others. It is necessary, however, to be aware that the conditions under which the protein is crystallized, or studied in solution, can affect the fold, and this has been illustrated with insulin. 

The great difficulty in understanding the evolution of a protein can be illustrated by cytochromes c, which are known to have a methionine and a histidine as heme ligands. The position of the methionine, especially, in the sequence of the proteins is very variable. Again cytochromes c have very different molecular weights. If this is true what is the implication for the overall fold The immediate neighbors of the heme, not bound to iron, include a tryptophan, almost invariable in structure but not in sequence position. How has this been evolved There is but one cytochrome c that has no tryptophan. I do not believe that we could follow evolution with confidence from sequences of single enzymes. Cytochrome c3 sequences show this very clearly, for these proteins, all from sulfur bacteria, show an enormous sequence variation [R. P. Ambler, Syst. Zool. 22, 554 (1974)]. There is no evidence that this is related to their evolution. 

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