Hypothesis: entatic versus ecstatic states in metalloproteins.

Wilfred R Hagen

doi:10.1039/c9mt00208a

Abstract

Over half a century ago the hypothesis was put forth that redox-active metal ions and multidentate protein ligands may combine to form a local state of entasis: an irregular symmetry intermediate between those dictated by coordination chemistry for the two redox states involved. Such an energetically poised domain would be at the basis of high activity (notably electron-transfer rates) in biological systems. Today the concept of the entatic state has become textbook material. Based on EPR spectroscopic data it is proposed here that poised, entatic states may only be of marginal existence; rather the occurrence of relatively wide distributions of coordination geometries (or: ecstatic states) afford a stochastic tuning of structure towards low-energy unimolecular transition states.

Highlights

Over half a century ago the hypothesis was put forth that redox-active metal ions and multidentate protein ligands may combine to form a local state of entasis: an irregular symmetry intermediate between those dictated by coordination chemistry for the two redox states involved
The key motive that inspired them to the formulation of this hypothesis was a number of perceived peculiarities in the optical and EPR spectroscopic properties of metalloproteins when compared to synthetic metal complexes, pointing to unusual environments in the former
The review builds on a series of earlier reviews by Comba around 2000, in Coordination Chemistry Reviews, in which the idea of entatic states in simple coordination compounds is conceived.[18,19,20]. In his 2000 review ‘‘Coordination compounds in the entatic state’’ Comba proclaims that ‘‘entasis is not confined to metalloproteins; reactions induced by metal-free enzymes or by small coordination compounds may involve strained, that is entatic states’’.19. In his 2003 review ‘‘Fit and misfit in metal ligand interactions’’ Comba gives a detailed view on entasis[20] which is too long to be reproduced here, but which nowhere addresses the question where the energy comes from to create entatic states

Summary

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Some years later Libscomb’s group publishes corrections to the previously reported metal coordinations but in a bottom-line statement they find it ‘unlikely that the differences in peptidase and esterase activities can be explained in terms of the entatic state hypothesis’’.12 With this another thread has run out, the entatic Co(II) returns in recent times in its low-spin form as part of the adenosylcobalamin cofactor. The joint groups of Watter and Krautler reported the biosynthesis of the cobalt-free B12 corrin and concluded from its X-ray structure that ‘‘the corrin ligand coordinates cobalt ions in de-symmetrized ‘entatic’ states’’.5 This assignment presents a head-on collision with the original entatic-state hypothesis which mandatorily required the presence of a protein (or a large structure with a flattened energy landscape). The entatic cobalamin is a present-day mark of an increasing trend that developed over the last two decades in which ever more non-protein, free coordination compounds were stickered as entatic-state complexes

Bootstrapping free coordination compounds into entatic states

Entatic states ascribed to coordination complexes

Distributed states in metalloproteins