4ZO3

AidC, a Dizinc Quorum-Quenching Lactonase, in complex with a product N-hexnoyl-L-homoserine

Summary for 4ZO3

• Entry DOI: 10.2210/pdb4zo3/pdb
• Related: 4ZO2
• Descriptor: Acylhomoserine lactonase, ZINC ION, N-hexanoyl-L-homoserine, ... (4 entities in total)
• Functional Keywords: quorum-quenching, n-acyl-l-homoserine, lactonase, dizinc, aidc, hydrolase
• Biological source: Chryseobacterium sp. StRB126
• Total number of polymer chains: 2
• Total formula weight: 66902.32

Authors

Mascarenhas, R.,Thomas, P.W.,Wu, C.-X.,Nocek, B.P.,Hoang, Q.,Fast, W.,Liu, D. (deposition date: 2015-05-05, release date: 2015-07-15, Last modification date: 2023-09-27)

Primary citation

Mascarenhas, R.,Thomas, P.W.,Wu, C.X.,Nocek, B.P.,Hoang, Q.Q.,Liu, D.,Fast, W.
Structural and Biochemical Characterization of AidC, a Quorum-Quenching Lactonase with Atypical Selectivity.
Biochemistry, 54:4342-4353, 2015

PubMed Abstract: 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 kcat/KM value of approximately 2 × 10(6) 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. 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. Implications for the catalytic mechanism of AHL lactonases are discussed.

PubMed: 26115006
DOI: 10.1021/acs.biochem.5b00499

Experimental method

X-RAY DIFFRACTION (1.67 Å)