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Information on EC 4.4.1.21 - S-ribosylhomocysteine lyase and Organism(s) Bacillus subtilis
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4.4.1.21 S-ribosylhomocysteine lyaseIUBMB Comments
Contains Fe2+. The 4,5-dihydroxypentan-2,3-dione formed spontaneously cyclizes and combines with borate to form an autoinducer (AI-2) in the bacterial quorum-sensing mechanism, which is used by many bacteria to control gene expression in response to cell density .
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Word Map
- 4.4.1.21
-
quorum
-
quorum-sensing
-
interspecies
- harveyi
- thioether
- 4,5-dihydroxy-2,3-pentanedione
- nucleosidase
-
luxs-dependent
-
furanone
- medicine
- analysis
The taxonomic range for the selected organisms is: Bacillus subtilis
The expected taxonomic range for this enzyme is: Bacteria, Eukaryota, Archaea
The expected taxonomic range for this enzyme is: Bacteria, Eukaryota, Archaea
Reaction Schemes
Synonyms
luxs protein, s-ribosylhomocysteinase, ai-2 synthase, s-ribosylhomocysteine lyase, autoinducer-2 synthase, s-ribosylhomocysteinelyase, s-ribosyl homocysteinase, 
more
topSYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
LuxS
S-ribosylhomocysteinase
REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
S-(5-deoxy-D-ribos-5-yl)-L-homocysteine = L-homocysteine + (4S)-4,5-dihydroxypentan-2,3-dione
S-(5-deoxy-D-ribos-5-yl)-L-homocysteine = L-homocysteine + (4S)-4,5-dihydroxypentan-2,3-dione
catalytic mechanism in which the metal ion catalyzes an intramolecular redox reaction, shifting the carbonyl group from the C-1 position to the C-3 position of the ribose. Subsequent beta-elimination at the C-4 and C-5 position releases homocysteine as a free thiol
-
S-(5-deoxy-D-ribos-5-yl)-L-homocysteine = L-homocysteine + (4S)-4,5-dihydroxypentan-2,3-dione
catalytic mechanism, the substrate may bind within the active site when its ribosyl moiety is in the alpha- or beta-furanose configuration or as a linear aldose, docking and molecular dynamics simulations
-
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
Bacillus subtilis can use methionine as sole sulfur source, the BsluxS knockout mutant grows poorly in the presence of methionine compared to the wild-type strain, methionine utilization requires first its conversion to homocysteine
PATHWAY SOURCE
PATHWAYS
BRENDA
-
-, -, -, -
SYSTEMATIC NAME
IUBMB Comments
S-(5-deoxy-D-ribos-5-yl)-L-homocysteine L-homocysteine-lyase [(4S)-4,5-dihydroxypentan-2,3-dione-forming]
Contains Fe2+. The 4,5-dihydroxypentan-2,3-dione formed spontaneously cyclizes and combines with borate to form an autoinducer (AI-2) in the bacterial quorum-sensing mechanism, which is used by many bacteria to control gene expression in response to cell density [2].
CAS REGISTRY NUMBER
COMMENTARY
37288-63-4
not distinguished from EC 3.2.1.148, formerly 3.3.1.3
SUBSTRATE
PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
(2R)-2-amino-4-[[(2S,4S)-2,4,5-trihydroxy-3-oxopentyl]sulfanyl]butanoic acid
L-homocysteine + ?
-
-
-
-
?
S-(5-deoxy-D-ribos-5-yl)-L-homocysteine
L-homocysteine + (4S)-4,5-dihydroxypentan-2,3-dione
S-(5-deoxy-D-ribos-5-yl)-L-homocysteine
L-homocysteine + (S)-4,5-dihydroxypentan-2,3-dione
-
-
-
?
S-ribosylhomocysteine
L-homocysteine + (S)-4,5-dihydroxy-2,3-pentanedione
assay at pH 7.0, 23°C
-
-
?
S-ribosylhomocysteine
L-homocysteine + (S)-4,5-dihydroxypentan-2,3-dione
-
-
-
?
S-(5-deoxy-D-ribos-5-yl)-L-homocysteine
L-homocysteine + (4S)-4,5-dihydroxypentan-2,3-dione
-
-
-
-
?
S-(5-deoxy-D-ribos-5-yl)-L-homocysteine
L-homocysteine + (4S)-4,5-dihydroxypentan-2,3-dione
-
furanose-containing S-ribosylhomocysteine
-
-
?
S-ribosylhomocysteine
L-homocysteine + 4,5-dihydroxy-2,3-pentanedione
-
-
-
-
?
S-ribosylhomocysteine
L-homocysteine + 4,5-dihydroxy-2,3-pentanedione
-
-
-
?
S-ribosylhomocysteine
L-homocysteine + 4,5-dihydroxy-2,3-pentanedione
-
-
-
-
?
S-ribosylhomocysteine
L-homocysteine + 4,5-dihydroxy-2,3-pentanedione
-
-
the reactive by-product of the LuxS-catalysed reaction 4,5-dihydroxy-2,3-pentanedione undergoes spontaneous cyclization reactions to form autoinducer 2
-
ir
S-ribosylhomocysteine
L-homocysteine + 4,5-dihydroxy-2,3-pentanedione
-
mechanism
-
-
?
S-ribosylhomocysteine
L-homocysteine + 4,5-dihydroxy-2,3-pentanedione
-
key step in biosynthesis pathway of type II autoinducer AI-2
-
-
?
NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
S-(5-deoxy-D-ribos-5-yl)-L-homocysteine
L-homocysteine + (4S)-4,5-dihydroxypentan-2,3-dione
-
-
-
-
?
S-ribosylhomocysteine
L-homocysteine + 4,5-dihydroxy-2,3-pentanedione
-
key step in biosynthesis pathway of type II autoinducer AI-2
-
-
?
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Co2+
Fe2+
Zinc
zinc-dependent metalloenzyme, each active site contains a zinc ion coordinated by the conserved residues His54, His58 and Cys126, and includes residues from both subunits
Zn2+
additional information
-
to gain insight into the catalytic mechanism of the unusual reaction and the function of the metal cofactor, an efficient expression and purification system is developed to produce LuxS enriched in either Fe2+, Co2+ or Zn2+
Fe2+
-
LuxS is a metalloenzyme containing a tetrahedrally coordinated Fe2+ ion in its active site
Zn2+
the metal center is composed of a Zn2+ atom coordinated by two histidines, a cysteine, and a solvent molecule
Zn2+
Zn2+ substitution produces an enzyme with 10fold lower activity
Zn2+
-
required for activity, in the wild-type the substrate's cyclic ribosyl moiety is positioned adjacent to the Zn2+ ion, while in the mutant C84A the noncyclic ribosyl is ligated to the Co2+ via its C2-O carbonyl oxygen
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
(2S)-2-amino-4-[(2R,3R)-2,3-dihydroxy-3-N-hydroxycarbamoylpropylmercapto] butyric acid
-
(2S)-2-amino-4-[(2R,3S)-2,3-dihydroxy-3-N-hydroxycarbamoylpropylmercapto] butyric acid
-
S-(1-amino-1,4-anhydro-1,5-dideoxy-D-ribitol-5-yl)-L-homocysteine
-
inhibition of Co(II)-substituted enzyme
S-(3,5-dideoxy-3-fluoro-1-O-methyl-D-xylofuranos-5-yl)-L-homocysteine
-
S-(4-amino-4,5-dideoxy-alpha/beta-D-ribofuranos-5-yl)-L-homocysteine
-
inhibition of Co(II)-substituted enzyme. The hemiaminal may undergo ring opening to form an aldehyde which may undergo the aldose-ketose isomerization reaction to form a 2-ketone, which presumably binds to the LuxS active site with higher affinity than the original ribose analogue
S-(4-amino-4,5-dideoxy-D-ribono-1,4-lactam-5-yl)-L-homocysteine
-
inhibition of Co(II)-substituted enzyme
additional information
5,6,7,8,9-pentadeoxy-6-fluoro-D-ribo-dec-5(Z)-enofuranuronate a S-ribosylhomocysteine analogue and 5,6-dideoxy-6-fluoro-D-ribo-hex-5-enofuranose a S-ribosylhomocysteine analogue have no inhibitory activity
-
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.0036
(2R)-2-amino-4-[[(2S,4S)-2,4,5-trihydroxy-3-oxopentyl]sulfanyl]butanoic acid
-
wild type enzyme
additional information
additional information
-
KM-values of enzyme forms enriched in either Fe2+, Co2+ or Zn2+
-
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.038
(2R)-2-amino-4-[[(2S,4S)-2,4,5-trihydroxy-3-oxopentyl]sulfanyl]butanoic acid
-
wild type enzyme
additional information
additional information
-
turnover numbers of enzyme forms enriched in either Fe2+, Co2+ or Zn2+
-
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.00037 - 0.0106
(2S)-2-amino-4-[(2R,3R)-2,3-dihydroxy-3-N-hydroxycarbamoylpropylmercapto] butyric acid
0.00072 - 0.0196
(2S)-2-amino-4-[(2R,3S)-2,3-dihydroxy-3-N-hydroxycarbamoylpropylmercapto] butyric acid
0.048
S-(1-amino-1,4-anhydro-1,5-dideoxy-D-ribitol-5-yl)-L-homocysteine
-
pH 7.0, 22°C
0.042
S-(3,5-dideoxy-3-fluoro-1-O-methyl-D-xylofuranos-5-yl)-L-homocysteine
pH 7.0, 23°C
0.0077
S-(3,5-dideoxy-3-fluoro-D-xylofuranos-5-yl)-L-homocysteine
pH 7.0, 23°C
0.055
S-(3,5-dideoxy-D-erythro-pentofuranos-5-yl)homocysteine
pH 7.0, 23°C
0.0035
S-(4-amino-4,5-dideoxy-alpha/beta-D-ribofuranos-5-yl)-L-homocysteine
-
pH 7.0, 22°C
0.037
S-(4-amino-4,5-dideoxy-D-ribono-1,4-lactam-5-yl)-L-homocysteine
-
pH 7.0, 22°C
0.0079
S-(5-deoxy-3-deoxy-3-bromo-D-xylofuranos-5-yl)-L-homocysteine
pH 7.0, 23°C
0.0106
S-(5-deoxy-3-deoxy-3-fluoro-D-xylofuranos-5-yl)-L-homocysteine
pH 7.0, 23°C
0.042
S-(5-deoxy-3-O-methyl-D-ribofuranos-5-yl)homocysteine
pH 7.0, 23°C
0.066
S-(5-deoxy-3-O-methyl-D-xylofuranos-5-yl)homocysteine
pH 7.0, 23°C
0.0079
S-[3-bromo-3,5-dideoxy-D-ribofuranos-5-yl]-L-homocysteine
-
wild type enzyme
0.0106
S-[3-fluoro-3,5-dideoxy-D-ribofuranos-5-yl]-L-homocysteine
-
wild type enzyme
0.00037
(2S)-2-amino-4-[(2R,3R)-2,3-dihydroxy-3-N-hydroxycarbamoylpropylmercapto] butyric acid
Co2+ substituted enzyme
0.00043
(2S)-2-amino-4-[(2R,3R)-2,3-dihydroxy-3-N-hydroxycarbamoylpropylmercapto] butyric acid
Fe2+ substituted enzyme
0.0106
(2S)-2-amino-4-[(2R,3R)-2,3-dihydroxy-3-N-hydroxycarbamoylpropylmercapto] butyric acid
Zn2+ substituted enzyme
0.00072
(2S)-2-amino-4-[(2R,3S)-2,3-dihydroxy-3-N-hydroxycarbamoylpropylmercapto] butyric acid
Co2+ substituted enzyme
0.00072
(2S)-2-amino-4-[(2R,3S)-2,3-dihydroxy-3-N-hydroxycarbamoylpropylmercapto] butyric acid
Fe2+ substituted enzyme
0.0196
(2S)-2-amino-4-[(2R,3S)-2,3-dihydroxy-3-N-hydroxycarbamoylpropylmercapto] butyric acid
Zn2+ substituted enzyme
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
additional information
-
luxS expression is detectable only at the base of fruiting bodies
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
physiological function
additional information
-
elucidation of the mechanism of the first stage of the enzyme catalytic process by docking and molecular dynamics simulations, overview. An active site water stably locates within the active site, it can facilitate ring-opening of either alpha-S-ribosylhomocysteine or beta-furanose, leading to formation of a common active-site-bound 2-keto-S-ribosylhomocysteine intermediate, without the need to pass through a linear aldose S-ribosylhomocysteine configuration. Catalytic importance of several active site residues including Ser6, His11, Arg39, Cys84, and Glu57
physiological function
produces precursor of type 2 autoinducer for bacterial cell-cell communication
physiological function
-
S-ribosyl homocysteinase is a key enzyme in the formation of the signaling molecule of QS-2, autoinducer II
UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable).
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable). PDB
SCOP
CATH
UNIPROT
ORGANISM
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
Co2+-substituted BsLuxS is cocrystallized with inhibitors (2S)-2-amino-4-[(2R,3S)-2,3-dihydroxy-3-N-hydroxycarbamoylpropylmercapto] butyric acid and (2S)-2-amino-4-[(2R,3R)-2,3-dihydroxy-3-N-hydroxycarbamoylpropylmercapto] butyric acid by the hanging drop vapor diffusion method
hanging drop vapor diffusion, inactive mutant C84A of Co2+-substituted LuxS is cocrystallized with the 2-ketone intermediate and the structure is determined to 1.8 A resolution
hanging-drop vapor diffusion method with ammonium sulfate as precipitant, structure at 1.6 A resolution
hanging-drop vapour diffusion method with ammonium sulfate as the precipitant. The crystals belong to the enantiomorphic space groups P6(1)22 or P6(5)22 with approximate unit-cell parameters A = b = 63.6, c = 151.5 A. The crystals diffract X-rays to at least 1.55 A resolution on a synchrotron-radiation source
-
structure of LuxS is determined at 1.2 A resolution, together with the binary complexes of LuxS with S-ribosylhomocysteine and homocysteine to 2.2 A and 2.3 A resolution, hanging-drop vapour diffusion method
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
C84A
C84D
C84A
-
site-directed mutagenesis, catalytically inactive mutant, the mutant contains a Co2+ ion, in the wild-type the substrate's cyclic ribosyl moiety is positioned adjacent to the Zn2+ ion, while in the mutant the noncyclic ribosyl is ligated to the Co2+ via its C2-O carbonyl oxygen
C84D
-
site-directed mutagenesis, the mutant shows reduced activity compared to the wild-type enzyme
GENERAL STABILITY
ORGANISM
UNIPROT
LITERATURE
absorption and electron paramagnetic resonance spectroscopic studies reveals that the active form of LuxS contains a metal-bound water and a thiolate ion at Cys-83, an invariant Arg-39 in the active site is partially responsible for stabilizing the thiolate anion of Cys-83
STORAGE STABILITY
ORGANISM
UNIPROT
LITERATURE
-80°C, when stored in the frozen form, the LuxS proteins are stable for at least 6 months
-
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
LuxS variants are overexpressed in Escherichia coli in their Fe2+, Zn2+- and Co2+-substituted forms
mutant LuxS variants are overexpressed in Escherichia coli in both Zn2+- and Co2+-substituted forms
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Das, S.K.; Sedelnikova, S.E.; Baker, P.J.; Ruzheinikov, S.N.; Foster, S.; Hartley, A.; Horsburgh, M.J.; Rice, D.W.
Cloning, purification, crystallization and preliminary crystallographic analysis of Bacillus subtilis LuxS
Acta Crystallogr. Sect. D
57
1324-1325
2001
Bacillus subtilis
Zhu, J.; Dizin, E.; Hu, X.; Wavreille, A.S.; Park, J.; Pei, D.
S-Ribosylhomocysteinase (LuxS) is a mononuclear iron protein
Biochemistry
42
4717-4726
2003
Bacillus subtilis
Ruzheinikov, S.N.; Das, S.K.; Sedelnikova, S.E.; Hartley, A.; Foster, S.J.; Horsburgh, M.J.; Cox, A.G.; McCleod, C.W.; Mekhalfia, A.; Blackburn, G.M.; Rice, D.W.; Baker, P.J.
The 1.2 A structure of a novel quorum-sensing protein, Bacillus subtilis LuxS
J. Mol. Biol.
313
111-122
2001
Bacillus subtilis (O34667)
Hilgers, M.T.; Ludwig, M.L.
Crystal structure of the quorum-sensing protein LuxS reveals a catalytic metal site
Proc. Natl. Acad. Sci. USA
98
11169-11174
2001
Bacillus subtilis (O34667)
Zhu, J.; Patel, R.; Pei, D.
Catalytic mechanism of S-ribosylhomocysteinase (LuxS): stereochemical course and kinetic isotope effect of proton transfer reactions
Biochemistry
43
10166-10172
2004
Bacillus subtilis, Vibrio harveyi
Rajan, R.; Zhu, J.; Hu, X.; Pei, D.; Bell, C.E.
Crystal structure of S-ribosylhomocysteinase (LuxS) in complex with a catalytic 2-ketone intermediate
Biochemistry
44
3745-3753
2005
Vibrio harveyi, Bacillus subtilis (O34667), Bacillus subtilis
Hullo, M.F.; Auger, S.; Soutourina, O.; Barzu, O.; Yvon, M.; Danchin, A.; Martin-Verstraete, I.
Conversion of methionine to cysteine in Bacillus subtilis and its regulation
J. Bacteriol.
189
187-197
2007
Bacillus subtilis (O34667), Bacillus subtilis 168 (O34667)
Zhu, J.; Knottenbelt, S.; Kirk, M.L.; Pei, D.
Catalytic mechanism of S-ribosylhomocysteinase: ionization state of active-site residues
Biochemistry
45
12195-12203
2006
Bacillus subtilis (O34667), Escherichia coli (P45578), Escherichia coli, Vibrio harveyi (Q9Z5X1)
Wnuk, S.F.; Lalama, J.; Robert, J.; Garmendia, C.A.
Novel S-ribosylhomocysteine analogues as potential inhibitors of LuxS enzyme
Nucleosides Nucleotides Nucleic Acids
26
1051-1055
2007
Bacillus subtilis (O34667)
Gopishetty, B.; Zhu, J.; Rajan, R.; Sobczak, A.J.; Wnuk, S.F.; Bell, C.E.; Pei, D.
Probing the catalytic mechanism of S-ribosylhomocysteinase (LuxS) with catalytic intermediates and substrate analogues
J. Am. Chem. Soc.
131
1243-1250
2009
Bacillus subtilis, Escherichia coli, Vibrio harveyi
Hardie, K.R.; Heurlier, K.
Establishing bacterial communities by word of mouth: LuxS and autoinducer 2 in biofilm development
Nat. Rev. Microbiol.
6
635-643
2008
Bacillus subtilis, Campylobacter jejuni, Escherichia coli, Haemophilus influenzae, Helicobacter pylori, Serratia plymuthica, Staphylococcus aureus, Vibrio harveyi
Wnuk, S.F.; Robert, J.; Sobczak, A.J.; Meyers, B.P.; Malladi, V.L.; Zhu, J.; Gopishetty, B.; Pei, D.
Inhibition of S-ribosylhomocysteinase (LuxS) by substrate analogues modified at the ribosyl C-3 position
Bioorg. Med. Chem.
17
6699-6706
2009
Bacillus subtilis (O34667)
Bhattacharyya, M.; Vishveshwara, S.
Functional correlation of bacterial LuxS with their quaternary associations: interface analysis of the structure networks
BMC Struct. Biol.
9
8
2009
Alkalihalobacillus clausii (Q5WDW1), Bacillus anthracis (Q81KF3), Bacillus cereus (Q816N5), Bacillus subtilis (O34667), Bifidobacterium longum (Q8G568), Campylobacter jejuni (Q9PN97), Clostridium perfringens (Q0SWJ6), Deinococcus geothermalis (Q1IW42), Deinococcus radiodurans (Q9RRU8), Escherichia coli (Q8X902), Haemophilus influenzae (P44007), Helicobacter pylori (Q9ZMW8), Lactobacillus acidophilus (Q5FK48), Lactobacillus johnsonii (Q74HV0), Limosilactobacillus reuteri (Q5QHW1), Psychromonas ingrahamii (A1SZZ2), Shigella flexneri (Q83JZ4), Staphylococcus aureus (Q6GEU1), Staphylococcus epidermidis (Q8CNI0), Streptococcus mutans (Q8DVK8), Streptococcus pyogenes (P0C0C7), Thermus thermophilus (Q72IE6), Vibrio cholerae (Q9KUG4)
Malladi, V.L.; Sobczak, A.J.; Meyer, T.M.; Pei, D.; Wnuk, S.F.
Inhibition of LuxS by S-ribosylhomocysteine analogues containing a [4-aza]ribose ring
Bioorg. Med. Chem.
19
5507-5519
2011
Bacillus subtilis
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