Protein aromatic clusters

Helical heptad repeat sequences have been reported to be well behaved although they are difficult to characterize by NMR spectroscopy due to spectral overlap. The motifs that have been shown to have native-like properties, and are not highly repetitive, have cores composed of aromatic amino acid side chains of, for example, phenylalanine and tryptophan. In four-helix bundle motifs [1, 2], the /1/la-motif BBAl [5] and the /1-sheet protein Betanova [9], the formation of the folded structure appears to be strongly dependent on such residues although the energetics have not been calculated by substitution studies. As a tentative rule, therefore, the probability of success in the design of a new protein is probably much higher if residues are included that can form aromatic clusters in the core (Fig. 5). 

Fig. 5. The aromatic cluster of the hydrophobic core of GTD-43, a helrx-loop-helrx dimer, and some of the assigned long-range NOEs that demonstrate the interactions of the aromatic side chains in the folded motif The formation of aromatic clusters has been observed in several designed proteins. Reproduced with permission from J Am Chem Soc (1997) 119 8598. ( 1997 ACS)...

S. K. Burley and G. A. Petsko cover the field of noncovalent interactions of proteins, with particular emphasis on weakly polar interactions. Their presentation of the whole field of electrostatic interactions should be of value to many workers in protein chemistry, but their special concern is with the weaker, but very important, interactions involving aromatic side chains, their orientation relative to one another, to oxygen and sulfur atoms, to amino groups, and to aromatic ligands that may bind to the protein. These interactions, only recently recognized for their influence on protein structure, play an important part in the formation of aromatic clusters in the interior of globular proteins and in other features of structure. The authors provide numerous illustrations of the principles involved, from recently determined structures, of both small molecules and proteins. 

Sequences of proteins containing Rieske-type clusters have been deduced from the complete operons of several dioxygenases these dioxygenases require electrons from NAD(P)H to convert aromatic compounds to cis-arene diols. The water-soluble dioxygenase systems consist of a reductase and a terminal dioxygenase many dioxygenases also contain a [2Fe-2S] ferredoxin (20). The terminal oxygenases contain a Rieske-type cluster and the ferredoxins may contain either a Rieske-type or a 4-cysteine coordinated [2Fe-2S] cluster. 

A complete systematic description of protein-metal complexation has yet to be presented, but it is apparent that many mechanisms are involved. Some proteins may participate in classical chelation interactions via polycarboxy clusters on their surfaces.2 Others interact with metals via coordination with polyhis-tidyl or other aromatic domains.13 5 Still others may interact with metals via sulfhydryl residues.13 The literature on immobilized metal affinity reveals examples of unexplained retention that may involve yet other mechanisms.1... 

Figure 2-16 Beta cylinders. (A) Stereoscopic a-carbon plot of plastocyanin, a copper-containing electron-transferring protein of chloroplasts. The copper atom at the top is also shown coordinated by the nitrogen atoms of two histidine side chains. The side chains of the aromatic residues phenylalanines 19,29, 35,41, 70, and 82 and tyrosines 80 and 83 are also shown. Most of these form an internal cluster.

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