4P2V: Structure Of The Ai-2 Processing Enzyme Lsrf In Complex With The Product Of The Lsrg Reaction P-hpd

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.
PDB ID: 4P2VDownload
MMDB ID: 123214
PDB Deposition Date: 2014/3/5
Updated in MMDB: 2014/10
Experimental Method:
x-ray diffraction
Resolution: 2.51  Å
Source Organism:
Similar Structures:
Biological Unit for 4P2V: decameric; determined by author and by software (PISA)
Molecular Components in 4P2V
Label Count Molecule
Proteins (10 molecules)
Uncharacterized Aldolase Lsrf(Gene symbol: lsrF)
Molecule annotation
Chemicals (10 molecules)
* Click molecule labels to explore molecular sequence information.

Citing MMDB