Structural and biochemical characterization of AidC, a quorum-quenching lactonase with atypical selectivity

Mascarenhas, Romila; Thomas, Pei W.; Wu, Chun -Xiang; Nocek, Boguslaw P.; Hoang, Quyen Q.; Liu, Dali; Fast, Walter

doi:10.1021/acs.biochem.5b00499

Structural and biochemical characterization of AidC, a quorum-quenching lactonase with atypical selectivity

Journal Article · Fri Jun 26 00:00:00 EDT 2015 · Biochemistry

DOI:https://doi.org/10.1021/acs.biochem.5b00499· OSTI ID:1263637

Mascarenhas, Romila ^[1]; Thomas, Pei W. ^[2]; Wu, Chun -Xiang ^[3]; Nocek, Boguslaw P. ^[4]; Hoang, Quyen Q. ^[3]; Liu, Dali ^[5]; Fast, Walter ^[6]

Loyola Univ. Chicago, Chicago, IL (United States). Dept. of Chemistry and Biochemistry
Univ. of Texas, Austin, TX (United States). College of Pharmacy
Indiana Univ. School of Medicine, Indianapolis, IN (United States)
Argonne National Lab. (ANL), Argonne, IL (United States)
Loyola Univ. Chicago, Chicago, IL (United States). Dept. of Chemistry and Biochemistry
Univ. of Texas, Austin, TX (United States). College of Pharmacy; Univ. of Texas, Austin, TX (United States). Center for Infectious Disease

Quorum-quenching catalysts are of interest for potential application as biochemical tools for interrogating interbacterial communication pathways, as antibiofouling agents, and as anti-infective agents in plants and animals. Herein, the structure and function of AidC, an N-acyl-l-homoserine lactone (AHL) lactonase from Chryseobacterium, is characterized. Steady-state kinetics show that zinc-supplemented AidC is the most efficient wild-type quorum-quenching enzymes characterized to date, with a k_cat/K_M value of approximately 2 × 10⁶ M^-1 s^-1 for N-heptanoyl-l-homoserine lactone. The enzyme has stricter substrate selectivity and significantly lower KM values (ca. 50 μM for preferred substrates) compared to those of typical AHL lactonases (ca. >1 mM). X-ray crystal structures of AidC alone and with the product N-hexanoyl-l-homoserine were determined at resolutions of 1.09 and 1.67 Å, respectively. Each structure displays as a dimer, and dimeric oligiomerization was also observed in solution by size-exclusion chromatography coupled with multiangle light scattering. Lastly, the structures reveal two atypical features as compared to previously characterized AHL lactonases: a "kinked" α-helix that forms part of a closed binding pocket that provides affinity and enforces selectivity for AHL substrates and an active-site His substitution that is usually found in a homologous family of phosphodiesterases. We discuss implications for the catalytic mechanism of AHL lactonases.

View Accepted Manuscript (DOE)

Research Organization:: Office of Scientific and Technical Information, Oak Ridge, TN (United States)

Sponsoring Organization:: USDOE

OSTI ID:: 1263637

Journal Information:: Biochemistry, Journal Name: Biochemistry Journal Issue: 28 Vol. 54; ISSN 0006-2960

Publisher:: American Chemical Society (ACS)Copyright Statement

Country of Publication:: United States

Language:: English

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