PDBsum entry 2fqt

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protein ligands metals links
Lyase PDB id
Protein chain
154 a.a. *
SO4 ×2
Waters ×137
* Residue conservation analysis
PDB id:
Name: Lyase
Title: Crystal structure of b.Subtilis luxs in complex with (2s)-2- [(2r,3s)-2,3-dihydroxy-3-n-hydroxycarbamoyl-propylmercapto] acid
Structure: S-ribosylhomocysteine lyase. Chain: a. Synonym: autoinducer-2 production protein luxs, ai-2 synthe protein. Engineered: yes
Source: Bacillus subtilis. Organism_taxid: 1423. Gene: luxs. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008.
Biol. unit: Dimer (from PDB file)
1.79Å     R-factor:   0.194     R-free:   0.226
Authors: G.Shen,R.Rajan,J.Zhu,C.E.Bell,D.Pei
Key ref: G.Shen et al. (2006). Design and synthesis of substrate and intermediate analogue inhibitors of S-ribosylhomocysteinase. J Med Chem, 49, 3003-3011. PubMed id: 16686542 DOI: 10.1021/jm060047g
18-Jan-06     Release date:   30-May-06    
Go to PROCHECK summary

Protein chain
Pfam   ArchSchema ?
O34667  (LUXS_BACSU) -  S-ribosylhomocysteine lyase
157 a.a.
154 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class: E.C.  - S-ribosylhomocysteine lyase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]

Autoinducer AI-2 Biosynthesis
      Reaction: S-(5-deoxy-D-ribos-5-yl)-L-homocysteine = L-homocysteine + (4S)-4,5- dihydroxypentan-2,3-dione
Bound ligand (Het Group name = H1D)
matches with 78.95% similarity
= L-homocysteine
+ (4S)-4,5- dihydroxypentan-2,3-dione
      Cofactor: Fe(2+)
Molecule diagrams generated from .mol files obtained from the KEGG ftp site
 Gene Ontology (GO) functional annotation 
  GO annot!
  Biological process     metabolic process   2 terms 
  Biochemical function     catalytic activity     5 terms  


DOI no: 10.1021/jm060047g J Med Chem 49:3003-3011 (2006)
PubMed id: 16686542  
Design and synthesis of substrate and intermediate analogue inhibitors of S-ribosylhomocysteinase.
G.Shen, R.Rajan, J.Zhu, C.E.Bell, D.Pei.
S-Ribosylhomocysteinase (LuxS) catalyzes the cleavage of the thioether linkage in S-ribosylhomocysteine (SRH) to produce homocysteine and 4,5-dihydroxy-2,3-pentanedione, the precursor of autoinducer 2. Inhibitors of LuxS should interfere with bacterial interspecies communication and potentially provide a novel class of antibacterial agents. LuxS utilizes a divalent metal ion as a Lewis acid during catalysis. In this work, a series of structural analogues of the substrate SRH and a 2-ketone intermediate were designed and synthesized. Kinetic studies indicate that the compounds act as reversible, competitive inhibitors against LuxS, with the most potent inhibitors having K(I) values in the submicromolar range. These represent the most potent LuxS inhibitors that have been reported to date. Cocrystal structures of LuxS bound with two of the inhibitors largely confirmed the design principles, i.e., the importance of both the homocysteine and ribose moieties in high-affinity binding to the LuxS active site.

Literature references that cite this PDB file's key reference

  PubMed id Reference
  21271798 V.C.Kalia, and H.J.Purohit (2011).
Quenching the quorum sensing system: potential antibacterial drug targets.
  Crit Rev Microbiol, 37, 121-140.  
19533733 H.Peng, Y.Cheng, N.Ni, M.Li, G.Choudhary, H.T.Chou, C.D.Lu, P.C.Tai, and B.Wang (2009).
Synthesis and evaluation of new antagonists of bacterial quorum sensing in Vibrio harveyi.
  ChemMedChem, 4, 1457-1468.  
18956421 N.Ni, M.Li, J.Wang, and B.Wang (2009).
Inhibitors and antagonists of bacterial quorum sensing.
  Med Res Rev, 29, 65.  
19682914 S.F.Wnuk, J.Robert, A.J.Sobczak, B.P.Meyers, V.L.Malladi, J.Zhu, B.Gopishetty, and D.Pei (2009).
Inhibition of S-ribosylhomocysteinase (LuxS) by substrate analogues modified at the ribosyl C-3 position.
  Bioorg Med Chem, 17, 6699-6706.  
18375129 S.F.Wnuk, J.Lalama, C.A.Garmendia, J.Robert, J.Zhu, and D.Pei (2008).
S-Ribosylhomocysteine analogues with the carbon-5 and sulfur atoms replaced by a vinyl or (fluoro)vinyl unit.
  Bioorg Med Chem, 16, 5090-5102.  
18180744 T.Defoirdt, N.Boon, P.Sorgeloos, W.Verstraete, and P.Bossier (2008).
Quorum sensing and quorum quenching in Vibrio harveyi: lessons learned from in vivo work.
  ISME J, 2, 19-26.  
17163561 F.E.Jacobsen, J.A.Lewis, and S.M.Cohen (2007).
The Design of Inhibitors for Medicinally Relevant Metalloproteins.
  ChemMedChem, 2, 152-171.  
18034729 K.W.Widmer, K.A.Soni, M.E.Hume, R.C.Beier, P.Jesudhasan, and S.D.Pillai (2007).
Identification of poultry meat-derived fatty acids functioning as quorum sensing signal inhibitors to autoinducer-2 (AI-2).
  J Food Sci, 72, M363-M368.  
The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time.