Information on EC 3.4.22.71 - sortase B

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The expected taxonomic range for this enzyme is: Bacilli

EC NUMBER
COMMENTARY
3.4.22.71
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RECOMMENDED NAME
GeneOntology No.
sortase B
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REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
The enzyme catalyses a cell wall sorting reaction in which a surface protein with a sorting signal containing a NXTN motif is cleaved. The resulting threonine carboxyl end of the protein is covalently attached to a pentaglycine cross-bridge of peptidoglycan.
show the reaction diagram
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REACTION TYPE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
hydrolysis of peptide bond
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SYNONYMS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
class B sortase
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class B sortase
Streptococcus pyogenes M1 SF370
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sortase B
Staphylococcus aureus Newman
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Spy0129
Streptococcus pyogenes M1 SF370
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SrtB
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CAS REGISTRY NUMBER
COMMENTARY
9033-39-0
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ORGANISM
COMMENTARY
LITERATURE
SEQUENCE CODE
SEQUENCE DB
SOURCE
strain EGD-e
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-
Manually annotated by BRENDA team
wild-type virulent strain EGD-e (serotype 1/2a)
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Manually annotated by BRENDA team
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Q7A650
UniProt
Manually annotated by BRENDA team
strain Newman
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Manually annotated by BRENDA team
Staphylococcus aureus Newman
strain Newman
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Manually annotated by BRENDA team
Streptococcus pyogenes M1 SF370
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Manually annotated by BRENDA team
GENERAL INFORMATION
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
physiological function
Q7A650
sortase attaches hemoproteins to the cell wall
physiological function
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the class B sortase is involved in pilus assembly
physiological function
Streptococcus pyogenes M1 SF370
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the class B sortase is involved in pilus assembly
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SUBSTRATE
PRODUCT                      
REACTION DIAGRAM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
(Substrate)
LITERATURE
(Substrate)
COMMENTARY
(Product)
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
Abz-KDFEVPTGVAM-Dap(Dnp)-NH2 + H2O
?
show the reaction diagram
Streptococcus pyogenes, Streptococcus pyogenes M1 SF370
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?
IsdC + H2O
?
show the reaction diagram
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the enzyme cleaves the C-terminal sorting signal of IsdC at the NPQTN motif and rethers the polypeptide to the pentaglycine cell wall cross-bridge. During catalysis, the active site cysteine of sortase and the cleaved substrate form an acyl intermediate, which is then resolved by the amino group of pentaglycine cross-bridges
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?
IsdC + H2O
?
show the reaction diagram
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the enzyme anchors the IsdC precursor with a C-terminal NPQTN motif sorting sognal, to the cell wall envelope. The sorting signal of IsdC is cleaved between threonine and asparagine of the NPQTN motif, and the carboxyl group of the thrteonine is amide-linked to the amino group of pentaglycine cross-bridges
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?
Lmo2185 + H2O
?
show the reaction diagram
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?
SvpA + H2O
?
show the reaction diagram
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anchoring of SvpA to the bacterial cell wall is specifically mediated by SrzB
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?
Lmo2186 + H2O
?
show the reaction diagram
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NPKSS is a sorting motif of Lmo2186. Recognition of NPKSS by SrtB, even when placed in the context of the heterologous sorting signal of Lmo2185. Proline at position 2, and not lysine at position 3, is essential for the recognition of NPKSS by SrtB
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?
additional information
?
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gram-positive pathogenic bacteria display proteins on their surface that play important roles during infection. In Staphylococcus aureus these surface proteins are anchored to the cell wall by two sortases, sortase A and sortaseB that recognize specific surface protein sorting signals. Sortase B plays a contributing role during the pathogenesis of staphylococcal infections
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additional information
?
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anchoring of SvpA to the bacterial cell wall is specifically mediated by SrzB. The enzyme is involved in the attachment of a subset of proteins to the cell wall, most likely by recognizing an NXZTN sorting motif. SrtB-mediated anchoring can be required to anchor surface proteins involved in the adaption of this microorganism to different environmental conditions
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additional information
?
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the svpA-srtB locus is regulated by iron availability, mediated by Fur
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additional information
?
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non-gel proteomics is a powerful technique to rapidly identify sortase substrates and to gain insights on potential sorting motifs. Two surface proteins, Lmo2185 and Lmo2186 are identified only when SrtB is active. The analysis of the peptides identified in these proteins suggests that SrtB of Listeria monocytogenes may recognize two different sorting motifs, NXZTN and NPKXZ
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additional information
?
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sortase B may be critical in the early stage of inhaltation anthrax
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additional information
?
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surface protein IsdC and sortase B are required for heme-iron scavenging of Bacillus anthracis
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NATURAL SUBSTRATES
NATURAL PRODUCTS
REACTION DIAGRAM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
(Substrate)
LITERATURE
(Substrate)
COMMENTARY
(Product)
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
IsdC + H2O
?
show the reaction diagram
-
the enzyme cleaves the C-terminal sorting signal of IsdC at the NPQTN motif and rethers the polypeptide to the pentaglycine cell wall cross-bridge. During catalysis, the active site cysteine of sortase and the cleaved substrate form an acyl intermediate, which is then resolved by the amino group of pentaglycine cross-bridges
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?
SvpA + H2O
?
show the reaction diagram
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anchoring of SvpA to the bacterial cell wall is specifically mediated by SrzB
-
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?
IsdC + H2O
?
show the reaction diagram
-
the enzyme anchors the IsdC precursor with a C-terminal NPQTN motif sorting sognal, to the cell wall envelope. The sorting signal of IsdC is cleaved between threonine and asparagine of the NPQTN motif, and the carboxyl group of the thrteonine is amide-linked to the amino group of pentaglycine cross-bridges
-
-
?
additional information
?
-
-
gram-positive pathogenic bacteria display proteins on their surface that play important roles during infection. In Staphylococcus aureus these surface proteins are anchored to the cell wall by two sortases, sortase A and sortaseB that recognize specific surface protein sorting signals. Sortase B plays a contributing role during the pathogenesis of staphylococcal infections
-
-
-
additional information
?
-
-
anchoring of SvpA to the bacterial cell wall is specifically mediated by SrzB. The enzyme is involved in the attachment of a subset of proteins to the cell wall, most likely by recognizing an NXZTN sorting motif. SrtB-mediated anchoring can be required to anchor surface proteins involved in the adaption of this microorganism to different environmental conditions
-
-
-
additional information
?
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the svpA-srtB locus is regulated by iron availability, mediated by Fur
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additional information
?
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surface protein IsdC and sortase B are required for heme-iron scavenging of Bacillus anthracis
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METALS and IONS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
Zn2+
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the asymmetric unit contains 19 bound Zn2+ ions
INHIBITORS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
(Z)-3-(2,5-dimethoxyphenyl)-2-(4-methoxyphenyl) acrylonitrile
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potential of this inhibitor for the treatment of Staphylococcus aureus infections
(Z)-3-(2,5-dimethoxyphenyl)-2-(4-methoxyphenyl) acrylonitrile
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50% inhibition with 0.0101 mg/ml
berberine chloride
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potential of this inhibitor for the treatment of Staphylococcus aureus infections
beta-sitosterol-3-O-glucopyranoside
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potential of this inhibitor for the treatment of Staphylococcus aureus infections
galangin
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IC50 for recombinant SrtB(DELTA30): 0.03837 mM, no antibacterial activity against Staphylococcus aureus
galangin-3-methyl ether
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IC50 for recombinant SrtB(DELTA30): 0.1136 mM, no antibacterial activity against Staphylococcus aureus
isorhamnetin
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IC50 for recombinant SrtB(DELTA30): 0.04335 mM, no antibacterial activity against Staphylococcus aureus
morin
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IC50 for recombinant SrtB(DELTA30): 0.00854 mM, no antibacterial activity against Staphylococcus aureus
myricetin
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IC50 for recombinant SrtB(DELTA30): 0.03689 mM, no antibacterial activity against Staphylococcus aureus
psammaplin A1
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potential of this inhibitor for the treatment of Staphylococcus aureus infections
quercetin
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IC50 for recombinant SrtB(DELTA30): 0.03328 mM, no antibacterial activity against Staphylococcus aureus
quercetin-3,3'-dimethyl ether
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IC50 for recombinant SrtB(DELTA30): 0.0603 mM, no antibacterial activity against Staphylococcus aureus
kaempferol
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IC50 for recombinant SrtB(DELTA30): 0.02455 mM, no antibacterial activity against Staphylococcus aureus
additional information
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aryl (beta-amino)ethyl ketones inhibit sortase enzymes. Inhibition of sortases occurs through an irreversible, covalent modification of their active site cysteine. Sortases specifically activate this class of molecules via beta-elimination, generating a reactive olefin intermediate that covalently modifies the cysteine thiol
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IC50 VALUE [mM]
IC50 VALUE [mM] Maximum
INHIBITOR
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
0.03837
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galangin
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IC50 for recombinant SrtB(DELTA30): 0.03837 mM, no antibacterial activity against Staphylococcus aureus
0.1136
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galangin-3-methyl ether
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IC50 for recombinant SrtB(DELTA30): 0.1136 mM, no antibacterial activity against Staphylococcus aureus
0.04335
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isorhamnetin
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IC50 for recombinant SrtB(DELTA30): 0.04335 mM, no antibacterial activity against Staphylococcus aureus
0.02455
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kaempferol
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IC50 for recombinant SrtB(DELTA30): 0.02455 mM, no antibacterial activity against Staphylococcus aureus
0.00854
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morin
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IC50 for recombinant SrtB(DELTA30): 0.00854 mM, no antibacterial activity against Staphylococcus aureus
0.03689
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myricetin
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IC50 for recombinant SrtB(DELTA30): 0.03689 mM, no antibacterial activity against Staphylococcus aureus
0.03328
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quercetin
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IC50 for recombinant SrtB(DELTA30): 0.03328 mM, no antibacterial activity against Staphylococcus aureus
0.0603
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quercetin-3,3'-dimethyl ether
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IC50 for recombinant SrtB(DELTA30): 0.0603 mM, no antibacterial activity against Staphylococcus aureus
PDB
SCOP
CATH
ORGANISM
Staphylococcus aureus (strain USA300)
Crystallization/COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
1.6 A resolution. Space group P2(1) with cell dimension of a = 40.47 A, b = 64.6 A, c = 42.96 A, alpha = 105.77°, beta = 105.77°, gamma = 90°
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SrtB in complex with aryl (beta-amino)ethyl ketone inhibitors. Analysis of the three-dimensional structure ofBacillusanthracissortaseBwithandwithoutinhibitorprovidesinsights into the mechanism of inhibition
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2.0 A resolution. Space group P2(1)2(1)2(1) with cell dimension of a = 71.208 A, b = 104.367 A, c = 58.087 A, alpha = beta = gamma = 90°
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hanging-drop vapor diffusion method. Crystal structure of SrtB-DELTA-N30 in complex with two active site inhibitors E64 and MTSET, and with the cell wall substrate analog tripleglycine
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hanging or sitting drop vapor diffusion method, using 10% (w/v) polyethylene glycol 3350, 0.2 M Zn(OAc)2, 0.1 M NaOAc, pH 6.2
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Purification/COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
Ni-charged HiTrap column chromatography and Superdex 200 gel filtration
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Cloned/COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
expression in Escherichia coli
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SrtADELTA24 is expressed in Escherichia coli
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expressed in Escherichia coli BL21 (DE3) pRP cells
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ENGINEERING
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
C221S
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the single residue mutation does not have noticeable effect on the secondary structure of the enzyme
C221S
Streptococcus pyogenes M1 SF370
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the single residue mutation does not have noticeable effect on the secondary structure of the enzyme
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additional information
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marked changes in the specificity profile of SrtA are obtained by replacing the beta6/beta7 loop in SrtA with the corresponding domain from SrtB
APPLICATION
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
medicine
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potential to be used as inhibitors for the treatment of Staphylococcus aureus infections: (Z)-3-(2,5-dimethoxyphenyl)-2-(4-methoxyphenyl) acrylonitrile, beta-sitosterol-3-O-glucopyranoside, berberine chloride and psammaplin A1