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Sci Rep. 2017 Jul 20;7(1):5977. doi: 10.1038/s41598-017-06330-9.

The relationship between folding and activity in UreG, an intrinsically disordered enzyme.

Author information

1
Laboratory of Bioinorganic Chemistry, Department of Pharmacy and Biotechnology, University of Bologna, Viale G. Fanin 40, Bologna, 40127, Italy.
2
Aix-Marseille Univ, CNRS, IMM (FR 3479), BIP (UMR 7281), 31 chemin Joseph Aiguier, Marseille, 13402, France.
3
Department of Molecular Medicine, University of South Florida, 12901 Bruce B. Downs Blvd., Tampa, MDC07, USA.
4
Aix-Marseille Univ, CNRS, IMM (FR 3479), BIP (UMR 7281), 31 chemin Joseph Aiguier, Marseille, 13402, France. emileo@imm.cnrs.fr.
5
Laboratory of Bioinorganic Chemistry, Department of Pharmacy and Biotechnology, University of Bologna, Viale G. Fanin 40, Bologna, 40127, Italy. barbara.zambelli@unibo.it.

Abstract

A growing body of literature on intrinsically disordered proteins (IDPs) led scientists to rethink the structure-function paradigm of protein folding. Enzymes are often considered an exception to the rule of intrinsic disorder (ID), believed to require a unique structure for catalysis. However, recent studies revealed the presence of disorder in several functional native enzymes. In the present work, we address the importance of dynamics for catalysis, by investigating the relationship between folding and activity in Sporosarcina pasteurii UreG (SpUreG), a P-loop GTPase and the first discovered native ID enzyme, involved in the maturation of the nickel-containing urease. The effect of denaturants and osmolytes on protein structure and activity was analyzed using circular dichroism (CD), Site-Directed Spin Labeling (SDSL) coupled to EPR spectroscopy, and enzymatic assays. Our data show that SpUreG needs a "flexibility window" to be catalytically competent, with both too low and too high mobility being detrimental for its activity.

PMID:
28729736
PMCID:
PMC5519622
DOI:
10.1038/s41598-017-06330-9
[Indexed for MEDLINE]
Free PMC Article

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