Chemistry and Physics Faculty Articles

Title

Conformational Dynamics of Metallo-β-lactamase CcrA During Catalysis Investigated by Using DEER Spectroscopy

Document Type

Article

Publication Date

2-10-2015

Publication Title

Journal of Biological Inorganic Chemistry

Keywords

Double electron–electron resonance (DEER), Metallo-β-lactamase (MβLs), Site-directed spin labeling (SDSL), Rapid freeze quench (RFQ), MTSL

ISSN

1432-1327

Volume

20

Issue/No.

3

First Page

585

Last Page

594

Abstract

Previous crystallographic and mutagenesis studies have implicated the role of a position-conserved hairpin loop in the metallo-β-lactamases in substrate binding and catalysis. In an effort to probe the motion of that loop during catalysis, rapid-freeze-quench double electron–electron resonance (RFQ-DEER) spectroscopy was used to interrogate metallo-β-lactamase CcrA, which had a spin label at position 49 on the loop and spin labels (at positions 82, 126, or 233) 20–35 Å away from residue 49, during catalysis. At 10 ms after mixing, the DEER spectra show distance increases of 7, 10, and 13 Å between the spin label at position 49 and the spin labels at positions 82, 126, and 233, respectively. In contrast to previous hypotheses, these data suggest that the loop moves nearly 10 Å away from the metal center during catalysis and that the loop does not clamp down on the substrate during catalysis. This study demonstrates that loop motion during catalysis can be interrogated on the millisecond time scale.

Comments

Copyright © 2015, SBIC

ORCID ID

https://orcid.org/0000-0003-2971-4878

DOI

10.1007/s00775-015-1244-8

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Peer Reviewed

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