Energised (entatic) States of Groups and of Secondary Structures in Proteins and Metalloproteins

Abstract

(Remived 25 luly 199.5) -EJB 9s 122YiOIn this review 1 have examined the fiinctional value of selected states of isolated groups in proteins energised away froni their expected ground states whether they ;ire observed with or without energy perturbation of larger parts of a protein structure. These cnergisations, found in the absence of substrates, are called 'entatic states of groups' [Vallec, B. L. Kr Williams, R. J. P. (1 968) Pn)c-. N~itl Accrcl. S Y . USA 59, 498-5051, A group can be part of an amino acid or any boutid metal ion or ciifitctor. In some particular cases the apoprotein, where the energised metitl ion or cofactor has been removed, or thc protein in which the energised amino acid hns been replaced, has the same back-hone structure a s the holoprotein and even side-chains are only slightly adjusted. This case is quite diffcrent from a condition of a group simultaneously energised with a protein fold, due to their combination, and which thcrefore involves cvnformutional changc in thc protein and the group and which may adjust the group while the protein tightens. The final condition is again stable but retiiovd of the group now niust result in ii reversed protein conformation change. This siinultancous energisation of both the adjustable protein and the gi-o~ip can be local, as in an induced fit or more extensive when it can be likened in sonic cases to 11 retching by rack action, or may involve a change from an almost random to ii structured protein when the group is encrgised in a very Iimitcd way. Thc various energisations must not be confused since they diffelfunctionally. The first can give rise to optimal heightened calitlylic (or other functional) potential 01' the local group but cannot be connected either to cxcitittion of other parts of a protcin as in induced fitting, or to a relay of energy (larger conformational change) in ilie pi-otein. Clearly it rcstricts the rate of exchange of a group. Induced fit can also give rise to group activntion, though to a sonizwhat reduccd degree, while increasing cxchange rate. A dcvicr such as it rack may rather give rise to ii mcchanical activity (message tlansmission), which is relayed ii large distiincc into the protein, and can only give considerably lowcr activation of individual groups but exchange may now be fast. The final citsc involvcs very modest energisation of the g r w p with gross rearrangement and onergisation of the protein ant1 nlay be associated with storage or carrier functions. The groups upon which I concentrate iirc tnetal ions since detaikd electronic and structural knowledge of their ground states are well known, allowing enctgisetl states to he easily detected, but the ideas apply equally to organic side-chains of proteins as will bc shown. A further energisation can arise from the addition of ii substrate to each kind of pmtein. In f:ict all the ideas of energisation applicable to groups having cyclic activity in permanent features of pi-oteiti structure are equally well applied to substrate binding or conversion of substrat...

The Functional Role of the Binuclear Metal Center in d-Aminoacylase

“…The differences in metal coordination are achieved by small movements of the metal ions and small shifts in the side chains of ligands to accommodate the metal binding. These results seem to be in agreement with the entatic state theory proposed by Williams, in which the metal site in a metalloprotein is configured by the protein matrix (36). The contrast between virtually identical ␤ sites and conformationally variable ␣ sites with a looser arrangement of ligands is consistent with their different affinities.…”

Geometric and Electronic Structure Contributions to Function in Bioinorganic Chemistry: Active Sites in Non-Heme Iron Enzymes

“…The differences between normal and blue Cu(I1) centers have been used to support the existence of a "rack" or "entatic" state in bioinorganic chemistry. (7)(8)(9) In an entatidrack state the protein imposes an unusual geometry on the active site which enhances its reactivity. (7)(8)(9) In blue Cu proteins, the protein rack (or entatic state) can be thought of as opposing the Jahn-Teller distortion, thus effecting little geometric change upon oxidation facilitating rapid electron transfer.…”

Establishing the entatic state in folding metallated Pseudomonas aeruginosa azurin

“…curved chevron ͉ cupredoxin ͉ metalloproteins T he entatic state occurs in proteins when a group, metal or nonmetal, is forced into an unusual, energetically strained geometric or electronic state (rack-induced state) (1)(2)(3)(4). Through the polypeptide's folding-induced rigidity, the protein fails to provide the expected geometry of ligating groups that would occur with freely mobile ligands in solution, thereby tuning the ligand's redox characteristics.…”

“…In metalloproteins, the metal ions are typically bound to the protein through one or more lone pair donors, endogenous biological ligands (e.g., the imidazole moiety of histidine, the carbonyl oxygen of the main chain or the side chain of an asparagine residue). In several cases the ligands are arranged such that an optimal geometry is precluded (1)(2)(3)(4). The resulting entatic state in a given metalloprotein is determined by the entire rigid protein scaffold in concert with the hydrogen-bonding network proximal to the coordination sphere (5,6).…”