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

• Published in: Journal of inorganic biochemistry Vol. 234; p. 111871
• Main Authors: Trindade, Inês B., Coelho, Anaísa, Cantini, Francesca, Piccioli, Mario, Louro, Ricardo O.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.09.2022
• Subjects: Electronic structure; Metal homeostasis and trafficking; Metalloproteins; NMR spectroscopy; Paramagnetic; Structural biology; Electronic structure; Metal homeostasis and trafficking; NMR spectroscopy; Metalloproteins; Structural biology; Paramagnetic
• ISSN: 0162-0134; 1873-3344
• DOI: 10.1016/j.jinorgbio.2022.111871

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. Like Janus, the Roman god of transition between old and new, biomolecular paramagnetic NMR spectroscopy is transitioning from the old vision of impossibly broad lines and dramatic chemical shifts to a vision of unique opportunities to explore the structure, function, dynamics and assembly of metalloproteins in vitro and in vivo. [Display omitted] •NMR structures of paramagnetic metalloproteins are under-represented in the pdb.•New experimental methods enhance the capacity to investigate paramagnetic systems.•Theoretical framework allows the interpretation of the paramagnetic effects.•Paramagnetic effects offer unique opportunities for structure-function studies.•Numerous key enzymes are metalloproteins and the field is ripe for exploration.