6WN0

The structure of a CoA-dependent acyl-homoserine lactone synthase, RpaI, with the adduct of SAH and p-coumaroyl CoA

Summary for 6WN0

• Entry DOI: 10.2210/pdb6wn0/pdb
• Descriptor: 4-coumaroyl-homoserine lactone synthase, COENZYME A, (2S)-4-({[(2S,3S,4R,5R)-5-(6-amino-9H-purin-9-yl)-3,4-dihydroxytetrahydrofuran-2-yl]methyl}sulfanyl)-2-{[(2E)-3-(cis-4-hydroxycyclohexa-2,5-dien-1-yl)prop-2-enoyl]amino}butanoic acid, ... (4 entities in total)
• Functional Keywords: acyl-homoserine lactone, coenzyme a, rpai, transferase
• Biological source: Rhodopseudomonas palustris
• Total number of polymer chains: 2
• Total formula weight: 50803.26

Authors

Dong, S.-H.,Nair, S.K. (deposition date: 2020-04-22, release date: 2020-05-13, Last modification date: 2023-10-18)

Primary citation

Dong, S.H.,Nhu-Lam, M.,Nagarajan, R.,Nair, S.K.
Structure-Guided Biochemical Analysis of Quorum Signal Synthase Specificities.
Acs Chem.Biol., 15:1497-1504, 2020

PubMed Abstract: Many bacteria use membrane-diffusible small molecule quorum signals to coordinate gene transcription in response to changes in cell density, known as quorum sensing (QS). Among these, acyl-homoserine lactones (AHL) are widely distributed in and are involved in controlling the expression of virulence genes and biofilm formation in pathogens, such as . AHL molecules are specifically biosynthesized by the cognate LuxI type AHL synthases using -adenosylmethionine (SAM) and either acyl carrier protein (ACP)- or CoA-coupled fatty acids through a two-step reaction. Here, we characterize a CoA-dependent LuxI synthase from that utilizes an aryl-CoA substrate that is environmentally derived, specifically -coumaric acid. We leverage structures of this aryl-CoA-dependent synthase, along with our prior studies of an acyl-CoA-dependent synthase, to identify residues that confer substrate chain specificity in these enzymes. We test our predictions by carrying out biochemical, kinetic, and structural characterization of representative AHL signal synthases. Our studies provide an understanding of various AHL synthases that may be deployed in synthetic biological applications and inform on the design of specific small molecule therapeutics that can restrict virulence by targeting quorum signaling.

PubMed: 32356962
DOI: 10.1021/acschembio.0c00142

Experimental method

X-RAY DIFFRACTION (1.85 Å)