NMR of paramagnetic metalloproteins in solution: Ubi venire, quo vadis?

Metalloproteins represent a substantial fraction of the proteome where they have an outsized contribution to enzymology. This stems from the reactivity of transition metals found in the active sites of numerous classes of enzymes that undergo redox and/or spin-state transitions. Notwithstanding, NMR structures of metalloproteins deposited in the PDB are under-represented and NMR studies exploring paramagnetic states are a minute fraction of the overall database content. This state of affairs contrasts with the early recognition that paramagnetic proteins offer unique opportunities for structure-function studies which are not available for diamagnetic proteins. Recent development of novel pulse sequences that minimize quenching of signal intensity that arises from the presence of a paramagnetic center in metalloproteins is extending even further the range of systems which can be studied by solution-state NMR. In this manuscript we review solution-state NMR applications to paramagnetic proteins, highlighting the developments in both methodologies and data interpretation, laying bare the vast range of opportunities for paramagnetic NMR to contribute to the understanding of structure and function of metalloenzymes and biomimetic metallocatalysts.

Automated summary

Metalloproteins play a significant role in enzymology, but their NMR structures are under-represented in the database. However, studying paramagnetic proteins offers unique opportunities for structure-function studies, and the development of new pulse sequences expands the range of systems that can be studied by solution-state NMR.