4P2V

Structure of the AI-2 processing enzyme LsrF in complex with the product of the LsrG reaction P-HPD

Summary for 4P2V

• Entry DOI: 10.2210/pdb4p2v/pdb
• Descriptor: Uncharacterized aldolase LsrF, (3R)-3-hydroxy-2,4-dioxopentyl dihydrogen phosphate (3 entities in total)
• Functional Keywords: thiolase, lyase
• Biological source: Escherichia coli
• Total number of polymer chains: 10
• Total formula weight: 322278.61

Authors

Miller, S.T.,Oh, I.K.,Xavier, K.B. (deposition date: 2014-03-04, release date: 2014-09-17, Last modification date: 2023-09-27)

Primary citation

Marques, J.C.,Oh, I.K.,Ly, D.C.,Lamosa, P.,Ventura, M.R.,Miller, S.T.,Xavier, K.B.
LsrF, a coenzyme A-dependent thiolase, catalyzes the terminal step in processing the quorum sensing signal autoinducer-2.
Proc.Natl.Acad.Sci.USA, 111:14235-14240, 2014

PubMed Abstract: The quorum sensing signal autoinducer-2 (AI-2) regulates important bacterial behaviors, including biofilm formation and the production of virulence factors. Some bacteria, such as Escherichia coli, can quench the AI-2 signal produced by a variety of species present in the environment, and thus can influence AI-2-dependent bacterial behaviors. This process involves uptake of AI-2 via the Lsr transporter, followed by phosphorylation and consequent intracellular sequestration. Here we determine the metabolic fate of intracellular AI-2 by characterizing LsrF, the terminal protein in the Lsr AI-2 processing pathway. We identify the substrates of LsrF as 3-hydroxy-2,4-pentadione-5-phosphate (P-HPD, an isomer of AI-2-phosphate) and coenzyme A, determine the crystal structure of an LsrF catalytic mutant bound to P-HPD, and identify the reaction products. We show that LsrF catalyzes the transfer of an acetyl group from P-HPD to coenzyme A yielding dihydroxyacetone phosphate and acetyl-CoA, two key central metabolites. We further propose that LsrF, despite strong structural homology to aldolases, acts as a thiolase, an activity previously undescribed for this family of enzymes. With this work, we have fully characterized the biological pathway for AI-2 processing in E. coli, a pathway that can be used to quench AI-2 and control quorum-sensing-regulated bacterial behaviors.

PubMed: 25225400
DOI: 10.1073/pnas.1408691111

Experimental method

X-RAY DIFFRACTION (2.51 Å)