Quantum mechanics and molecular mechanics study of the reaction mechanism of quorum quenching enzyme: N-acyl homoserine lactonase with C6-HSL

RSC Advances ◽  
2016 ◽  
Vol 6 (28) ◽  
pp. 23396-23402 ◽  
Author(s):  
Shujun Zhang ◽  
Hao Su ◽  
Guangcai Ma ◽  
Yongjun Liu
Keyword(s):  
Quantum Mechanics ◽  
Reaction Mechanism ◽  
Molecular Mechanics ◽  
Lactone Ring ◽  
Quorum Quenching ◽  
Homoserine Lactone ◽  
Ester Bond ◽  
Acyl Homoserine Lactone

N-Acyl-homoserine lactonase fromOchrobactrumsp. strain (AidH) is a novel AHL (N-acyl-homoserine lactone)-lactonase that hydrolyzes the ester bond of the homoserine lactone ring of AHLs.

scholarly journals The Komagataeibacter europaeus GqqA is the prototype of a novel bifunctional N-Acyl-homoserine lactone acylase with prephenate dehydratase activity

2021 ◽  
Author(s):  
Manuel Ferrer ◽  
Laura Fernandes-Lopez ◽  
Sven Falke ◽  
Markus Perbandt ◽  
Winfried Hinrichs ◽  
...  
Keyword(s):  
Catalytic Domain ◽  
Lactone Ring ◽  
Phylogenetic Analyses ◽  
Quorum Quenching ◽  
Homoserine Lactone ◽  
Docking Studies ◽  
Protein Domain ◽  
Amide Bond ◽  
Binding Motif ◽  
Acyl Homoserine Lactone

Abstract Previously, we reported the isolation of a quorum quenching protein (QQ), designated GqqA, from Komagataeibacter europaeus CECT 8546 that is highly homologous to prephenate dehydratases (PDT) 1. GqqA strongly interfered with N-acyl-homoserine lactone (AHL) quorum sensing signals from Gram-negative bacteria and affected biofilm formation in its native host strain Komagataeibacter europaeus. Here we present and discuss data identifying GqqA as a novel acylase. ESI-MS-MS data showed unambiguously that GqqA hydrolyzes the amide bond of the acyl side-chain of AHL molecules, but not the lactone ring. Consistent with this observation the protein sequence does not carry a conserved Zn2+ binding motif, known to be essential for metal-dependent lactonases, but in fact harboring the typical periplasmatic binding protein domain (PBP domain), acting as catalytic domain. We report structural details for the native structure at 2.5 Å resolution and for a truncated GqqA structure at 1.7 Å. The structures obtained highlight that GqqA acts as a dimer and complementary docking studies indicate that the lactone ring of the substrate binds within a cleft of the PBP domain and interacts with polar residues Y16, S17 and T174. The biochemical and phylogenetic analyses imply that GqqA represents the first member of a novel type of QQ family enzymes.

scholarly journals The Komagataeibacter europaeus GqqA is the prototype of a novel bifunctional N-Acyl-homoserine lactone acylase with prephenate dehydratase activity

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Nadine Werner ◽  
Katrin Petersen ◽  
Christel Vollstedt ◽  
Pablo Perez Garcia ◽  
Jennifer Chow ◽  
...  
Keyword(s):  
Catalytic Domain ◽  
Lactone Ring ◽  
Phylogenetic Analyses ◽  
Quorum Quenching ◽  
Homoserine Lactone ◽  
Docking Studies ◽  
Protein Domain ◽  
Amide Bond ◽  
Binding Motif ◽  
Acyl Homoserine Lactone

AbstractPreviously, we reported the isolation of a quorum quenching protein (QQ), designated GqqA, from Komagataeibacter europaeus CECT 8546 that is highly homologous to prephenate dehydratases (PDT) (Valera et al. in Microb Cell Fact 15, 88. 10.1186/s12934-016-0482-y, 2016). GqqA strongly interfered with N-acyl-homoserine lactone (AHL) quorum sensing signals from Gram-negative bacteria and affected biofilm formation in its native host strain Komagataeibacter europaeus. Here we present and discuss data identifying GqqA as a novel acylase. ESI–MS–MS data showed unambiguously that GqqA hydrolyzes the amide bond of the acyl side-chain of AHL molecules, but not the lactone ring. Consistent with this observation the protein sequence does not carry a conserved Zn2+ binding motif, known to be essential for metal-dependent lactonases, but in fact harboring the typical periplasmatic binding protein domain (PBP domain), acting as catalytic domain. We report structural details for the native structure at 2.5 Å resolution and for a truncated GqqA structure at 1.7 Å. The structures obtained highlight that GqqA acts as a dimer and complementary docking studies indicate that the lactone ring of the substrate binds within a cleft of the PBP domain and interacts with polar residues Y16, S17 and T174. The biochemical and phylogenetic analyses imply that GqqA represents the first member of a novel type of QQ family enzymes.

scholarly journals A single point mutation converts a glutaryl-7-aminocephalosporanic acid acylase into an N-acyl-homoserine lactone acylase

2021 ◽  
Author(s):  
Shereen A. Murugayah ◽  
Gary B. Evans ◽  
Joel D. A. Tyndall ◽  
Monica L. Gerth
Keyword(s):  
Single Point ◽  
Quorum Quenching ◽  
Homoserine Lactone ◽  
Site Directed Mutagenesis ◽  
Saturation Mutagenesis ◽  
Single Amino Acid ◽  
Single Point Mutation ◽  
Acyl Homoserine Lactone ◽  
Signalling Molecules ◽  
Single Amino Acid Residue

Abstract Objective To change the specificity of a glutaryl-7-aminocephalosporanic acid acylase (GCA) towards N-acyl homoserine lactones (AHLs; quorum sensing signalling molecules) by site-directed mutagenesis. Results Seven residues were identified by analysis of existing crystal structures as potential determinants of substrate specificity. Site-saturation mutagenesis libraries were created for each of the seven selected positions. High-throughput activity screening of each library identified two variants—Arg255Ala, Arg255Gly—with new activities towards N-acyl homoserine lactone substrates. Structural modelling of the Arg255Gly mutation suggests that the smaller side-chain of glycine (as compared to arginine in the wild-type enzyme) avoids a key clash with the acyl group of the N-acyl homoserine lactone substrate. Conclusions Mutation of a single amino acid residue successfully converted a GCA (with no detectable activity against AHLs) into an AHL acylase. This approach may be useful for further engineering of ‘quorum quenching’ enzymes.

scholarly journals Diversity of Acyl Homoserine Lactone Molecules in Anaerobic Membrane Bioreactors Treating Sewage at Psychrophilic Temperatures

Membranes ◽  
2020 ◽  
Vol 10 (11) ◽  
pp. 320
Author(s):  
Shamas Tabraiz ◽  
Burhan Shamurad ◽  
Evangelos Petropoulos ◽  
Alex Charlton ◽  
Obaidullah Mohiudin ◽  
...  
Keyword(s):  
Membrane Bioreactor ◽  
Quorum Quenching ◽  
Homoserine Lactone ◽  
Membrane Bioreactors ◽  
Acyl Homoserine Lactone ◽  
Mixed Liquor ◽  
Anaerobic Membrane Bioreactor ◽  
Anaerobic Bioreactors ◽  
New Information ◽  
Anaerobic Membrane Bioreactors

This study explores the types of acyl homoserine lactone (AHL) and their concentrations in different compartments of different conventional anaerobic bioreactors: (i) an upflow anaerobic membrane bioreactor (UAnMBR, biofilm/mixed liquor (sludge)); (ii) an anaerobic membrane bioreactor (AnMBR, biofilm/mixed liquor (sludge)); and (iii) an upflow sludge blanket (UASB, sludge only), all operating at 15 °C. Ten types of the AHL, namely C4-HSL, 3-oxo-C4-HSL, C6-HSL, 3-oxo-C6-HSL, C8-HSL, 3-oxo-C8-HSL, C10-HSL, 3-oxo-C10-HSL, C12-HSL, and 3-oxo-C12-HSL, which were investigated in this study, were found in UAnMBR and UASB, whilst only six of them (C4-HSL, 3-oxo-C4-HSL, C8-HSL, C10-HSL, 3-oxo-C10-HSL, and C12-HSL) were found in AnMBR. Concentrations of total AHL were generally higher in the biofilm than the sludge for both membrane bioreactors trialed. C10-HSL was the predominant AHL found in all reactors (biofilm and sludge) followed by C4-HSL and C8-HSL. Overall, the UAnMBR biofilm and sludge had 10-fold higher concentrations of AHL compared to the AnMBR. C10-HSL was only correlated with bacteria (p < 0.05), whilst other types of AHL were correlated with both bacteria and archaea. This study improves our understanding of AHL-mediated Quorum Sensing (QS) in the biofilms/sludge of UAnMBR and AnMBR, and provides new information that could contribute to the development of quorum quenching anti-fouling strategies in such systems.

Reaction Mechanism of Human Renin Studied by Quantum Mechanics/Molecular Mechanics (QM/MM) Calculations

ACS Catalysis ◽  
2014 ◽  
Vol 4 (11) ◽  
pp. 3869-3876 ◽  
Author(s):  
Ana R. Calixto ◽  
Natércia F. Brás ◽  
Pedro A. Fernandes ◽  
Maria J. Ramos
Keyword(s):  
Quantum Mechanics ◽  
Reaction Mechanism ◽  
Molecular Mechanics ◽  
Human Renin
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