Metal-induced structural variability of mononuclear metal-binding sites from a database perspective

Metalloproteins are ubiquitous in all kingdoms of life. Their role and function are tightly related to the local structure of the metal-binding site. In this regard, the MetalPDB database is an invaluable tool since it stores the 3D structure of metal-binding sites and of their corresponding apo forms. In this work, we exploited MetalPDB to compute extensive statistics over >3000 clusters of mononuclear sites about the rearrangements occurring upon change in metalation state. For each cluster, we matched the holo and apo sites so that it was possible to average the distances between all possible pairs of Cα and donor atoms and thus quantitatively assess structural variations by computing the Δ values (mean apo distance - mean holo distance). For most of the structures the backbone is rigid with little to no rearrangement, while donor atoms experience significant changes of their relative position when the metal is removed. Sodium and potassium sites are an exception to this general observation. This is most likely caused by their preference for coordination by the main-chain oxygen atoms, making the rearrangement of donor atoms superimposable to that of the backbone. Magnesium and calcium show a different behavior, despite their chemical similarity: calcium sites undergo a larger reorganization upon metalation although both metals have similar percentage of backbone oxygen as donor atoms. We ascribe this observation to the structural and energetic factors regulating the selectivity for calcium over magnesium.