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31  structures 1787  species 0  interactions 1957  sequences 4  architectures

Family: LuxS (PF02664)

Summary: S-Ribosylhomocysteinase (LuxS)

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This is the Wikipedia entry entitled "S-ribosylhomocysteine lyase". More...

S-ribosylhomocysteine lyase Edit Wikipedia article

S-ribosylhomocysteine lyase
EC number4.4.1.21
CAS number37288-63-4
IntEnzIntEnz view
ExPASyNiceZyme view
MetaCycmetabolic pathway
PDB structuresRCSB PDB PDBe PDBsum
Gene OntologyAmiGO / QuickGO
S-Ribosylhomocysteinase (LuxS)
PDB 1joe EBI.jpg
crystal structure of autoinducer-2 production protein (luxs) from Haemophilus influenzae
Pfam clanCL0094

In enzymology, a S-ribosylhomocysteine lyase (EC is an enzyme that catalyzes the chemical reaction

S-(5-deoxy-D-ribos-5-yl)-L-homocysteine L-homocysteine + (4S)-4,5-dihydroxypentan-2,3-dione
A product of S-adenosyl -L-methionine (AdoMet)-dependent methylation, S-adenosyl-L- homocysteine is first hydrolyzed to S-ribosyl-L-homocysteine and adenine.

Hence, this enzyme has one substrate, S-(5-deoxy-D-ribos-5-yl)-L-homocysteine, and two products, L-homocysteine and (4S)-4,5-dihydroxypentan-2,3-dione. (DPD) which is the precursor of autoinducer-2.


This enzyme belongs to the family of lyases, specifically the class of carbon-sulfur lyases. The systematic name of this enzyme class is S-(5-deoxy-D-ribos-5-yl)-L-homocysteine L-homocysteine-lyase [(4S)-4,5-dihydroxypentan-2,3-dione-forming]. Other names in common use include S-ribosylhomocysteinase, and LuxS. This enzyme participates in methionine metabolism.

Structure and function

LuxS is a homodimeric iron-dependent metalloenzyme containing two identical tetrahedral metal-binding sites similar to those found in peptidases and amidases.[1] Furthermore, LuxS is involved in the synthesis of autoinducer AI-2 (autoinducer-2), which mediates quorum sensing in roughly half of bacterial species. AI-2, a furanosyl borate diester, is a small signaling molecule generated by bacteria. LuxS converts S-ribosylhomocysteine to homocysteine and 4,5-dihydroxy-2,3-pentanedione (DPD); DPD can then spontaneously cyclisize to active AI-2.[2][3] AI-2 is a signalling molecule that is believed to act in cross-species communication by regulating niche-specific genes with diverse functions, such as toxin production, biofilm formation, sporulation, and virulence gene expression, in various bacteria, often in response to population density. The AI-2 formation pathway begins with S-adenosyl-L-homocysteine (AdoHcy), which is hydrolyzed to S-ribosyl-L-homocysteine (SRH) and adenine by S-adenosyl-L-homocysteine/5’-methylthioadenosine nucleosidase (SAHN or MTAN, EC (8-10). LuxS cleaves S-ribosyl-homocysteine to form L-homocysteine (Hcy) and 4,5-dihydroxy-2,3-pentanedione (DPD), which can then spontaneously cyclisize to active AI-2 (11-15).[2][3] An unequivocally AI-2 related behavior was found to be restricted primarily to bacteria bearing known AI-2 receptor genes.[4] Thus, while it is certainly true that some bacteria can respond to AI-2, it is doubtful that it is always being produced for purposes of signaling.

Clinical significance

LuxS influences iron uptake in pneumococcal species, which also affects biofilm formation.[5] LuxS mutant D39luxS has reduced virulence when compared to wild type studies done on the intranasal channels of mice, and experiments have shown that this mutant also has significantly decreased biofilm formation capabilities.[5]


  1. ^ Rajan R, Zhu J, Hu X, Pei D, Bell CE (March 2005). "Crystal structure of S-ribosylhomocysteinase (LuxS) in complex with a catalytic 2-ketone intermediate". Biochemistry. 44 (10): 3745–53. doi:10.1021/bi0477384. PMID 15751951.
  2. ^ a b van Houdt R, Moons P, Jansen A, Vanoirbeek K, Michiels CW (September 2006). "Isolation and functional analysis of luxS in Serratia plymuthica RVH1". FEMS Microbiology Letters. 262 (2): 201–9. doi:10.1111/j.1574-6968.2006.00391.x. PMID 16923076. Cite error: The named reference "pmid16923076" was defined multiple times with different content (see the help page).
  3. ^ a b Zhu J, Patel R, Pei D (August 2004). "Catalytic mechanism of S-ribosylhomocysteinase (LuxS): stereochemical course and kinetic isotope effect of proton transfer reactions". Biochemistry. 43 (31): 10166–72. doi:10.1021/bi0491088. PMID 15287744. Cite error: The named reference "pmid15287744" was defined multiple times with different content (see the help page).
  4. ^ Rezzonico F, Duffy B (September 2008). "Lack of genomic evidence of AI-2 receptors suggests a non-quorum sensing role for luxS in most bacteria". BMC Microbiology. 8: 154. doi:10.1186/1471-2180-8-154. PMC 2561040. PMID 18803868.
  5. ^ a b Trappetti C, Potter AJ, Paton AW, Oggioni MR, Paton JC (November 2011). "LuxS mediates iron-dependent biofilm formation, competence, and fratricide in Streptococcus pneumoniae". Infection and Immunity. 79 (11): 4550–8. doi:10.1128/IAI.05644-11. PMC 3257940. PMID 21875962.

Further reading

This article incorporates text from the public domain Pfam and InterPro: IPR003815

This page is based on a Wikipedia article. The text is available under the Creative Commons Attribution/Share-Alike License.

This tab holds the annotation information that is stored in the Pfam database. As we move to using Wikipedia as our main source of annotation, the contents of this tab will be gradually replaced by the Wikipedia tab.

S-Ribosylhomocysteinase (LuxS) Provide feedback

This family consists of the LuxS protein involved in autoinducer AI2 synthesis and its hypothetical relatives. S-ribosylhomocysteinase (LuxS) catalyses the cleavage of the thioether bond in S-ribosylhomocysteine (SRH) to produce homocysteine and 4,5-dihydroxy-2,3-pentanedione (DPD), the precursor of type II bacterial quorum sensing molecule.

Literature references

  1. Surette MG, Miller MB, Bassler BL; , Proc Natl Acad Sci U S A 1999;96:1639-1644.: Quorum sensing in Escherichia coli, Salmonella typhimurium, and Vibrio harveyi: a new family of genes responsible for autoinducer production. PUBMED:9990077 EPMC:9990077

  2. Zhu J, Patel R, Pei D; , Biochemistry 2004;43:10166-10172.: Catalytic mechanism of S-ribosylhomocysteinase (LuxS): stereochemical course and kinetic isotope effect of proton transfer reactions. PUBMED:15287744 EPMC:15287744

  3. Zhu J, Hu X, Dizin E, Pei D; , J Am Chem Soc 2003;125:13379-13381.: Catalytic mechanism of S-ribosylhomocysteinase (LuxS): direct observation of ketone intermediates by 13C NMR spectroscopy. PUBMED:14583032 EPMC:14583032

  4. Zhu J, Dizin E, Hu X, Wavreille AS, Park J, Pei D; , Biochemistry 2003;42:4717-4726.: S-Ribosylhomocysteinase (LuxS) is a mononuclear iron protein. PUBMED:12705835 EPMC:12705835

External database links

This tab holds annotation information from the InterPro database.

InterPro entry IPR003815

In bacteria, the regulation of gene expression in response to changes in cell density is called quorum sensing. Quorum-sensing bacteria produce, release, and respond to hormone-like molecules (autoinducers) that accumulate in the external environment as the cell population grows. For example, enteric bacteria use quorum sensing to regulate several traits that allow them to establish and maintain infection in their host, including motility, biofilm formation, and virulence-specific genes [ PUBMED:17133078 ]. The LuxS/AI-2 system is one of several quorum sensing mechanisms. AI-2 (autoinducer-2) is a signalling molecule that functions in interspecies communication by regulating niche-specific genes with diverse functions in various bacteria, often in response to population density. LuxS (S-ribosylhomocysteinase; EC ) is an autoinducer-production protein that has a metabolic function as a component of the activated methyl cycle. LuxS converts S-ribosylhomocysteine to homocysteine and 4,5-dihydroxy-2,3-pentanedione (DPD); DPD can then spontaneously cyclise to active AI-2 [ PUBMED:16923076 , PUBMED:15287744 ]. LuxS is a homodimeric iron-dependent metalloenzyme containing two identical tetrahedral metal-binding sites similar to those found in peptidases and amidases [ PUBMED:15751951 ].

Gene Ontology

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Domain organisation

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Pfam Clan

This family is a member of clan Peptidase_ME (CL0094), which has the following description:

All members of this clan are characterised by a HXXEH motif, which is is involved in zinc binding. Furthermore all members adopt an alpha and beta fold. More specifically, there us a four to six stranded antiparallel beta sheet surrounded by five helices. However, LuxS (PFAM:PF02664) is not a peptidase, although its hydrolytic mechanism of catalysis appears to be conserved [1].

The clan contains the following 7 members:

LuxS M16C_assoc Peptidase_M16 Peptidase_M16_C Peptidase_M16_M Peptidase_M44 tRNA_SAD


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Curation and family details

This section shows the detailed information about the Pfam family. You can see the definitions of many of the terms in this section in the glossary and a fuller explanation of the scoring system that we use in the scores section of the help pages.

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Seed source: COG1854
Previous IDs: none
Type: Family
Sequence Ontology: SO:0100021
Author: Bashton M , Bateman A , Adamkewicz J
Number in seed: 131
Number in full: 1957
Average length of the domain: 147.90 aa
Average identity of full alignment: 41 %
Average coverage of the sequence by the domain: 92.72 %

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HMM build commands:
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 57096847 -E 1000 --cpu 4 HMM pfamseq
Model details:
Parameter Sequence Domain
Gathering cut-off 20.3 20.3
Trusted cut-off 20.9 20.8
Noise cut-off 19.4 18.7
Model length: 154
Family (HMM) version: 17
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Species distribution

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Archea Archea Eukaryota Eukaryota
Bacteria Bacteria Other sequences Other sequences
Viruses Viruses Unclassified Unclassified
Viroids Viroids Unclassified sequence Unclassified sequence


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For those sequences which have a structure in the Protein DataBank, we use the mapping between UniProt, PDB and Pfam coordinate systems from the PDBe group, to allow us to map Pfam domains onto UniProt sequences and three-dimensional protein structures. The table below shows the structures on which the LuxS domain has been found. There are 31 instances of this domain found in the PDB. Note that there may be multiple copies of the domain in a single PDB structure, since many structures contain multiple copies of the same protein sequence.

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