3RKR

Crystal structure of a metagenomic short-chain oxidoreductase (SDR) in complex with NADP

Summary for 3RKR

• Entry DOI: 10.2210/pdb3rkr/pdb
• Descriptor: Short chain oxidoreductase, NADP NICOTINAMIDE-ADENINE-DINUCLEOTIDE PHOSPHATE, SULFATE ION, ... (4 entities in total)
• Functional Keywords: rossmann fold, oxidoreductase
• Biological source: uncultured bacterium Bio5
• Total number of polymer chains: 4
• Total formula weight: 112452.80

Authors

Mayerhofer, H.,Bijtenhoorn, P.,Streit, W.R.,Mueller-Dieckmann, J. (deposition date: 2011-04-18, release date: 2011-11-30, Last modification date: 2023-09-13)

Primary citation

Bijtenhoorn, P.,Mayerhofer, H.,Muller-Dieckmann, J.,Utpatel, C.,Schipper, C.,Hornung, C.,Szesny, M.,Grond, S.,Thurmer, A.,Brzuszkiewicz, E.,Daniel, R.,Dierking, K.,Schulenburg, H.,Streit, W.R.
A novel metagenomic short-chain dehydrogenase/reductase attenuates Pseudomonas aeruginosa biofilm formation and virulence on Caenorhabditis elegans.
Plos One, 6:e26278-e26278, 2011

PubMed Abstract: In Pseudomonas aeruginosa, the expression of a number of virulence factors, as well as biofilm formation, are controlled by quorum sensing (QS). N-Acylhomoserine lactones (AHLs) are an important class of signaling molecules involved in bacterial QS and in many pathogenic bacteria infection and host colonization are AHL-dependent. The AHL signaling molecules are subject to inactivation mainly by hydrolases (Enzyme Commission class number EC 3) (i.e. N-acyl-homoserine lactonases and N-acyl-homoserine-lactone acylases). Only little is known on quorum quenching mechanisms of oxidoreductases (EC 1). Here we report on the identification and structural characterization of the first NADP-dependent short-chain dehydrogenase/reductase (SDR) involved in inactivation of N-(3-oxo-dodecanoyl)-L-homoserine lactone (3-oxo-C(12)-HSL) and derived from a metagenome library. The corresponding gene was isolated from a soil metagenome and designated bpiB09. Heterologous expression and crystallographic studies established BpiB09 as an NADP-dependent reductase. Although AHLs are probably not the native substrate of this metagenome-derived enzyme, its expression in P. aeruginosa PAO1 resulted in significantly reduced pyocyanin production, decreased motility, poor biofilm formation and absent paralysis of Caenorhabditis elegans. Furthermore, a genome-wide transcriptome study suggested that the level of lasI and rhlI transcription together with 36 well known QS regulated genes was significantly (≥10-fold) affected in P. aeruginosa strains expressing the bpiB09 gene in pBBR1MCS-5. Thus AHL oxidoreductases could be considered as potent tools for the development of quorum quenching strategies.

PubMed: 22046268
DOI: 10.1371/journal.pone.0026278

Experimental method

X-RAY DIFFRACTION (2.42 Å)