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Mattsson J, Phoeurk C, Schierholz L, Mushtaq AU, Rodriguez Buitrago JA, Rogne P, Sauer-Eriksson AE, Wolf-Watz M
Biochemistry 64 (20) 4281-4295 [2025-10-21; online 2025-10-03]
Conformational dynamics is a fundamental aspect of enzymatic catalysis that, for example, can be linked to ligand binding and release, assembly of the active site, and the catalytic mechanism. The essential and metabolic enzyme adenylate kinase (AK) undergoes large-scale conformational changes in response to binding of its substrates ATP and AMP. As such, it has been intensely studied in search of linkages between dynamics and catalysis. For a complex conformational change to occur in a protein, whether it is of an induced fit or conformational selection nature, changes at several hinges are often required. Here, based on a comparative structure-function analysis of AK enzymes from E. coli and the archaea Odinarchaeota and from human AK1, we found that conformational changes in the enzymes are to a varying degree linked to bending, fraying, or unfolding/folding events of the termini of α-helices observed in various structural hot spots of the enzymes. The findings contribute with a mechanistic angle to how enzymatic dynamics and catalysis relate to the plasticity of the termini of α-helices.
PubMed 41042980
DOI 10.1021/acs.biochem.5c00306
Crossref 10.1021/acs.biochem.5c00306