Energised (entatic) states of groups and of secondary structures in proteins and metalloproteins.
In this review I have examined the functional value of selected states of isolated groups in proteins energised away from their expected ground states whether they are observed with or without energy perturbation of larger parts of a protein structure. These energisations, found in the absence of substrates, are called 'entatic states of groups' [Vallee, B. L. & Williams, R. J. P. (1968) Proc. Natl Acad. Sci. USA 59, 498-505]. A group can be part of an amino acid or any bound metal ion or cofactor. In some particular cases the apoprotein, where the energised metal ion or cofactor has been removed, or the protein in which the energised amino acid has been replaced, has the same back-bone structure as the holoprotein and even side-chains are only slightly adjusted. This case is quite different from a condition of a group simultaneously energised with a protein fold, due to their combination, and which therefore involves conformational change in the protein and the group and which may adjust the group while the protein tightens. The final condition is again stable but removal of the group now must result in a reversed protein conformation change. This simultaneous energisation of both the adjustable protein and the group can be local, as in an induced fit or more extensive when it can be likened in some cases to a stretching by rack action, or may involve a change from an almost random to a structured protein when the group is energised in a very limited way. The various energisations must not be confused since they differ functionally. The first can give rise to optimal heightened catalytic (or other functional) potential of the local group but cannot be connected either to excitation of other parts of a protein as in induced fitting, or to a relay of energy (larger conformational change) in the protein. Clearly it restricts the rate of exchange of a group. Induced fit can also give rise to group activation, though to a somewhat reduced degree, while increasing exchange rate. A device such as a rack may rather give rise to a mechanical activity (message transmission), which is relayed a large distance into the protein, and can only give considerably lower activation of individual groups but exchange may now be fast. The final case involves very modest energisation of the group with gross rearrangement and energisation of the protein and may be associated with storage or carrier functions. The groups upon which I concentrate are metal ions since detailed electronic and structural knowledge of their ground states are well known, allowing energised states to be easily detected, but the ideas apply equally to organic side-chains of proteins as will be shown. A further energisation can arise from the addition of a substrate to each kind of protein. In fact all the ideas of energisation applicable to groups having cyclic activity in permanent features of protein structure are equally well applied to substrate binding or conversion of substrates through excited states to products.
University of Oxford, Inorganic Chemistry Laboratory, England.
R J
RJ
Williams
D001059:Apoproteins / Q000737:chemistry; D002256:Carbonic Anhydrases / Q000737:chemistry; D008667:Metalloproteins / Q000737:chemistry*; D010084:Oxidation-Reduction; D017433:Protein Structure, Secondary; D013482:Superoxide Dismutase / Q000737:chemistry
D001059:Apoproteins; D008667:Metalloproteins; D013482:Superoxide Dismutase; D002256:Carbonic Anhydrases