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Information on EC 2.3.2.20 - cyclo(L-leucyl-L-phenylalanyl) synthase
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2.3.2.20 cyclo(L-leucyl-L-phenylalanyl) synthaseIUBMB Comments
The reaction proceeds following a ping-pong mechanism forming a covalent intermediate between an active site serine and the L-phenylalanine residue . The protein, found in the bacterium Streptomyces noursei, also forms cyclo(L-phenylalanyl-L-phenylalanyl), cyclo(L-methionyl-L-phenylalanyl), cyclo(L-phenylalanyl-L-tyrosyl) and cyclo(L-methionyl-L-tyrosyl) .
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Word Map
- 2.3.2.20
-
cdpss
-
diketopiperazine
- synthetases
-
aminoacylated
-
2,5-diketopiperazines
-
nonribosomal
-
trna-dependent
- prenyltransferase
-
aa-trnas
-
aarss
-
class-i
- nocardiopsis
-
prenylation
-
hijack
-
bond-forming
-
ping-pong
- synthesis
-
tryptophan-containing
-
synthetase-like
- noursei
The enzyme appears in viruses and cellular organisms
Reaction Schemes
Synonyms
cyclodipeptide synthases, cyclodipeptide synthase, 
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SYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
AlbC
CDPS
CDPS39
cFL synthase
-
-
-
-
cyclodipeptide synthase
Nbra-CDPS
Ndas_1148
O3I_025450
Rgry-CDPS
RICGR_0139
AlbC
-
-
-
-
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REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
L-leucyl-tRNALeu + L-phenylalanyl-tRNAPhe = tRNALeu + tRNAPhe + cyclo(L-leucyl-L-phenylalanyl)
L-leucyl-tRNALeu + L-phenylalanyl-tRNAPhe = tRNALeu + tRNAPhe + cyclo(L-leucyl-L-phenylalanyl)
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-
-
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L-leucyl-tRNALeu + L-phenylalanyl-tRNAPhe = tRNALeu + tRNAPhe + cyclo(L-leucyl-L-phenylalanyl)
ping-pong mechanism with a covalent intermediate in which L-Phe is transferred from Phe-tRNA(Phe) to an active serine
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SYSTEMATIC NAME
IUBMB Comments
L-leucyl-tRNALeu:L-phenylalanyl-tRNAPhe leucyltransferase (cyclizing)
The reaction proceeds following a ping-pong mechanism forming a covalent intermediate between an active site serine and the L-phenylalanine residue [2]. The protein, found in the bacterium Streptomyces noursei, also forms cyclo(L-phenylalanyl-L-phenylalanyl), cyclo(L-methionyl-L-phenylalanyl), cyclo(L-phenylalanyl-L-tyrosyl) and cyclo(L-methionyl-L-tyrosyl) [1].
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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
L-leucyl-tRNALeu + L-phenylalanyl-tRNAPhe
tRNALeu + tRNAPhe + cyclo(L-leucyl-L-phenylalanyl)
L-phenylalanyl-tRNAPhe + L-leucyl-tRNALeu
tRNAPhe + tRNALeu + cyclo(L-phenylalanyl-L-leucyl)
-
-
-
?
L-phenylalanyl-tRNAPhe + L-methionyl-tRNAMet
tRNAPhe + tRNAMet + cyclo(L-phenylalanyl-L-methionyl)
L-phenylalanyl-tRNAPhe + L-phenylalanyl-tRNAPhe
2 tRNAPhe + cyclo(L-phenylalanyl-L-phenylalanyl)
L-phenylalanyl-tRNAPhe + L-prolyl-tRNAPro
tRNAPhe + tRNAPro + cyclo(L-phenylalanyl-L-prolyl)
-
-
-
-
?
L-phenylalanyl-tRNAPhe + L-tyrosinyl-tRNATyr
tRNAPhe + tRNATyr + cyclo(L-phenylalanyl-L-tyrosinyl)
-
-
-
-
?
L-tryptophanyl-tRNATrp + L-tryptophanyl-tRNATrp
2 tRNATrp + cyclo(L-tryptophanyl-L-tryptophanyl)
-
-
-
-
?
L-tyrosinyl-tRNATyr + L-prolyl-tRNAPro
tRNATyr + tRNAPro + cyclo(L-tyrosinyl-L-prolyl)
-
-
-
-
?
L-tyrosinyl-tRNATyr + L-valyl-tRNAVal
tRNATyr + tRNAVal + cyclo(L-tyrosinyl-L-valyl)
-
-
-
-
?
L-leucyl-tRNALeu + L-phenylalanyl-tRNAPhe
tRNALeu + tRNAPhe + cyclo(L-leucyl-L-phenylalanyl)
-
second best activity
-
-
?
L-leucyl-tRNALeu + L-phenylalanyl-tRNAPhe
tRNALeu + tRNAPhe + cyclo(L-leucyl-L-phenylalanyl)
-
second best activity
-
-
?
L-leucyl-tRNALeu + L-phenylalanyl-tRNAPhe
tRNALeu + tRNAPhe + cyclo(L-leucyl-L-phenylalanyl)
-
highest activity
-
-
?
L-leucyl-tRNALeu + L-phenylalanyl-tRNAPhe
tRNALeu + tRNAPhe + cyclo(L-leucyl-L-phenylalanyl)
-
-
-
?
L-leucyl-tRNALeu + L-phenylalanyl-tRNAPhe
tRNALeu + tRNAPhe + cyclo(L-leucyl-L-phenylalanyl)
-
intermediate product of the biosynthetic pathway to albonoursin, cyclo(alpha,beta-dehydroPhe-alpha,beta-dehydroLeu)
-
?
L-leucyl-tRNALeu + L-phenylalanyl-tRNAPhe
tRNALeu + tRNAPhe + cyclo(L-leucyl-L-phenylalanyl)
-
the enzyme uses more efficiently Phe-tRNAPhe than any of the Leu-tRNALeu. The efficiency of cyclo(L-phenylalanyl-L-phenylalanyl) synthesis is not affected by the presence of Leu-tRNALeuGAG or Leu-tRNALeuTAA indicating that these molecules do not compete with Phe-tRNAPhe for binding to the enzyme. In contrast, Leu-tRNALeuCAA, Leu-tRNALeuTAG or or Leu-tRNALeuCAG isoacceptors inhibit cyclo(L-phenylalanyl-L-phenylalanyl) synthesis revealing a competition with Phe-tRNAPhe
-
-
?
L-phenylalanyl-tRNAPhe + L-methionyl-tRNAMet
tRNAPhe + tRNAMet + cyclo(L-phenylalanyl-L-methionyl)
-
lowest activity
-
-
?
L-phenylalanyl-tRNAPhe + L-methionyl-tRNAMet
tRNAPhe + tRNAMet + cyclo(L-phenylalanyl-L-methionyl)
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lowest activity
-
-
?
L-phenylalanyl-tRNAPhe + L-methionyl-tRNAMet
tRNAPhe + tRNAMet + cyclo(L-phenylalanyl-L-methionyl)
-
lowest activity
-
-
?
L-phenylalanyl-tRNAPhe + L-phenylalanyl-tRNAPhe
2 tRNAPhe + cyclo(L-phenylalanyl-L-phenylalanyl)
-
highest activity
-
-
?
L-phenylalanyl-tRNAPhe + L-phenylalanyl-tRNAPhe
2 tRNAPhe + cyclo(L-phenylalanyl-L-phenylalanyl)
-
highest activity
-
-
?
L-phenylalanyl-tRNAPhe + L-phenylalanyl-tRNAPhe
2 tRNAPhe + cyclo(L-phenylalanyl-L-phenylalanyl)
-
second best activity
-
-
?
L-phenylalanyl-tRNAPhe + L-phenylalanyl-tRNAPhe
2 tRNAPhe + cyclo(L-phenylalanyl-L-phenylalanyl)
-
-
-
?
additional information
?
-
cyclodipeptide synthases (CDPSs) use two aminoacyl-tRNAs to catalyze the formation of two peptide bonds leading to cyclodipeptides
-
-
-
additional information
?
-
cyclodipeptide synthases (CDPSs) use two aminoacyl-tRNAs to catalyze the formation of two peptide bonds leading to cyclodipeptides
-
-
-
additional information
?
-
cyclodipeptide synthases (CDPSs) use two aminoacyl-tRNAs to catalyze the formation of two peptide bonds leading to cyclodipeptides
-
-
-
additional information
?
-
-
the enzyme does not accept other aromatic aminoacyl-tRNA substrates than L-tryptophanyl-tRNA
-
-
?
additional information
?
-
cyclodipeptide synthases (CDPSs) use two aminoacyl-tRNAs to catalyze the formation of two peptide bonds leading to cyclodipeptides
-
-
-
additional information
?
-
Rickettsiella grylli ATCC 700358
cyclodipeptide synthases (CDPSs) use two aminoacyl-tRNAs to catalyze the formation of two peptide bonds leading to cyclodipeptides
-
-
-
additional information
?
-
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in vivo method for incorporating non-canonical amino acids (ncAAs) into 2,5-DKPs using cyclodipeptide synthases (CDPSs), exploitation of the natural ability of aminoacyl-tRNA synthetases to load ncAAs onto tRNAs, substrate specificity, detailed overview
-
-
-
additional information
?
-
enzyme AlbC uses aminoacyl-tRNAs to synthesize various cyclodipeptides, including the reactions of cyclo(L-tyrosyl-L-tyrosyl) synthase, EC 2.3.2.21, and cyclo(L-leucyl-L-leucyl) synthase, EC 2.3.2.22
-
-
?
additional information
?
-
-
enzyme AlbC uses aminoacyl-tRNAs to synthesize various cyclodipeptides, including the reactions of cyclo(L-tyrosyl-L-tyrosyl) synthase, EC 2.3.2.21, and cyclo(L-leucyl-L-leucyl) synthase, EC 2.3.2.22
-
-
?
additional information
?
-
assembly of the cyclo-Phe-Leu precursor of albonoursin is catalyzed by CDPS AlbC, which also yields a variety of other cyclic dipeptides as minor products
-
-
-
additional information
?
-
cyclodipeptide synthases (CDPSs) use two aminoacyl-tRNAs to catalyze the formation of two peptide bonds leading to cyclodipeptides
-
-
-
additional information
?
-
mechanism of cyclization with the participation of Y202 in the catalytic function, roles of important residues E182, Y178, N40, and H203, detailed overview
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-
-
additional information
?
-
the AlbC catalytic cycle begins with the binding of the first aa-tRNA, with its aminoacyl moiety accommodated in a surface-accessible pocket P1 and transferred onto a conserved serine residue to form an aminoacyl-enzyme intermediate. The second aa-tRNA interacts with this intermediate so that its aminoacyl moiety, accommodated in a wide cavity P2, is transferred to the aminoacyl-enzyme to form a dipeptidyl-enzyme intermediate. Finally, the dipeptidyl moiety undergoes an intramolecular cyclization leading to the final cyclodipeptide
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-
-
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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
L-leucyl-tRNALeu + L-phenylalanyl-tRNAPhe
tRNALeu + tRNAPhe + cyclo(L-leucyl-L-phenylalanyl)
L-phenylalanyl-tRNAPhe + L-leucyl-tRNALeu
tRNAPhe + tRNALeu + cyclo(L-phenylalanyl-L-leucyl)
-
-
-
?
L-phenylalanyl-tRNAPhe + L-methionyl-tRNAMet
tRNAPhe + tRNAMet + cyclo(L-phenylalanyl-L-methionyl)
L-phenylalanyl-tRNAPhe + L-phenylalanyl-tRNAPhe
2 tRNAPhe + cyclo(L-phenylalanyl-L-phenylalanyl)
L-phenylalanyl-tRNAPhe + L-tyrosinyl-tRNATyr
tRNAPhe + tRNATyr + cyclo(L-phenylalanyl-L-tyrosinyl)
-
-
-
-
?
L-tryptophanyl-tRNATrp + L-tryptophanyl-tRNATrp
2 tRNATrp + cyclo(L-tryptophanyl-L-tryptophanyl)
-
-
-
-
?
L-leucyl-tRNALeu + L-phenylalanyl-tRNAPhe
tRNALeu + tRNAPhe + cyclo(L-leucyl-L-phenylalanyl)
-
second best activity
-
-
?
L-leucyl-tRNALeu + L-phenylalanyl-tRNAPhe
tRNALeu + tRNAPhe + cyclo(L-leucyl-L-phenylalanyl)
-
second best activity
-
-
?
L-leucyl-tRNALeu + L-phenylalanyl-tRNAPhe
tRNALeu + tRNAPhe + cyclo(L-leucyl-L-phenylalanyl)
-
highest activity
-
-
?
L-leucyl-tRNALeu + L-phenylalanyl-tRNAPhe
tRNALeu + tRNAPhe + cyclo(L-leucyl-L-phenylalanyl)
-
the enzyme uses more efficiently Phe-tRNAPhe than any of the Leu-tRNALeu. The efficiency of cyclo(L-phenylalanyl-L-phenylalanyl) synthesis is not affected by the presence of Leu-tRNALeuGAG or Leu-tRNALeuTAA indicating that these molecules do not compete with Phe-tRNAPhe for binding to the enzyme. In contrast, Leu-tRNALeuCAA, Leu-tRNALeuTAG or or Leu-tRNALeuCAG isoacceptors inhibit cyclo(L-phenylalanyl-L-phenylalanyl) synthesis revealing a competition with Phe-tRNAPhe
-
-
?
L-phenylalanyl-tRNAPhe + L-methionyl-tRNAMet
tRNAPhe + tRNAMet + cyclo(L-phenylalanyl-L-methionyl)
-
lowest activity
-
-
?
L-phenylalanyl-tRNAPhe + L-methionyl-tRNAMet
tRNAPhe + tRNAMet + cyclo(L-phenylalanyl-L-methionyl)
-
lowest activity
-
-
?
L-phenylalanyl-tRNAPhe + L-methionyl-tRNAMet
tRNAPhe + tRNAMet + cyclo(L-phenylalanyl-L-methionyl)
-
lowest activity
-
-
?
L-phenylalanyl-tRNAPhe + L-phenylalanyl-tRNAPhe
2 tRNAPhe + cyclo(L-phenylalanyl-L-phenylalanyl)
-
highest activity
-
-
?
L-phenylalanyl-tRNAPhe + L-phenylalanyl-tRNAPhe
2 tRNAPhe + cyclo(L-phenylalanyl-L-phenylalanyl)
-
highest activity
-
-
?
L-phenylalanyl-tRNAPhe + L-phenylalanyl-tRNAPhe
2 tRNAPhe + cyclo(L-phenylalanyl-L-phenylalanyl)
-
second best activity
-
-
?
additional information
?
-
-
the enzyme does not accept other aromatic aminoacyl-tRNA substrates than L-tryptophanyl-tRNA
-
-
?
additional information
?
-
assembly of the cyclo-Phe-Leu precursor of albonoursin is catalyzed by CDPS AlbC, which also yields a variety of other cyclic dipeptides as minor products
-
-
-
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INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
azetidine-2-carboxylic acid
-
Aze, production of cyclo(Tyr-Val) is slightly decreased by the addition of Aze, which may reflect competition of Aze versus Val
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ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
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GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
evolution
metabolism
physiological function
additional information
evolution
CDPSs fall into two subfamilies, NYH and XYP, characterized by the presence of specific sequence signatures. Comparison of the XYP and NYH enzymes shows that the two subfamilies mainly differ in the first half of their Rossmann fold. The XYP and NYH motifs correspond to two structural solutions to facilitate the reactivity of the catalytic serine residue. The CDPS from Fluoribacter dumoffii belongs to the XYP subfamily
evolution
CDPSs fall into two subfamilies, NYH and XYP, characterized by the presence of specific sequence signatures. Comparison of the XYP and NYH enzymes shows that the two subfamilies mainly differ in the first half of their Rossmann fold. The XYP and NYH motifs correspond to two structural solutions to facilitate the reactivity of the catalytic serine residue. The CDPS from Nocardia brasiliensis belongs to the XYP subfamily
evolution
CDPSs fall into two subfamilies, NYH and XYP, characterized by the presence of specific sequence signatures. Comparison of the XYP and NYH enzymes shows that the two subfamilies mainly differ in the first half of their Rossmann fold. The XYP and NYH motifs correspond to two structural solutions to facilitate the reactivity of the catalytic serine residue. The CDPS from Rickettsiella grylli belongs to the XYP subfamily
evolution
CDPSs fall into two subfamilies, NYH and XYP, characterized by the presence of specific sequence signatures. Comparison of the XYP and NYH enzymes shows that the two subfamilies mainly differ in the first half of their Rossmann fold. The XYP and NYH motifs correspond to two structural solutions to facilitate the reactivity of the catalytic serine residue. The CDPS from Streptomyces noursei belongs to the NYH subfamily
evolution
methyltransferase homologues are commonly encoded within putative CDPS gene clusters, yet methyltransferases from only two of these clusters have been characterized to date. One leads to methylated members of the nocazine/XR334 (e.g. XR334) family and the other catalyzes DKP N-methylation of cyclo(L-tryptophanyl-L-tryptophanyl) (cWW) to yield dimethyl-cyclo-Trp-Trp (Me2-cWW)
evolution
the entire family of CDPSs can be classified into two subfamilies, so called NYH and XYP, characterized by the presence of specific sequence signatures at positions N40, Y202, and H203. The residues, N40 and H203 are suggested to play a role in the stabilization of other residues in the catalytic center and are not conserved among the CDPS family, but are important for the function of AlbC
evolution
-
CDPSs fall into two subfamilies, NYH and XYP, characterized by the presence of specific sequence signatures. Comparison of the XYP and NYH enzymes shows that the two subfamilies mainly differ in the first half of their Rossmann fold. The XYP and NYH motifs correspond to two structural solutions to facilitate the reactivity of the catalytic serine residue. The CDPS from Nocardia brasiliensis belongs to the XYP subfamily
-
evolution
-
methyltransferase homologues are commonly encoded within putative CDPS gene clusters, yet methyltransferases from only two of these clusters have been characterized to date. One leads to methylated members of the nocazine/XR334 (e.g. XR334) family and the other catalyzes DKP N-methylation of cyclo(L-tryptophanyl-L-tryptophanyl) (cWW) to yield dimethyl-cyclo-Trp-Trp (Me2-cWW)
-
evolution
-
methyltransferase homologues are commonly encoded within putative CDPS gene clusters, yet methyltransferases from only two of these clusters have been characterized to date. One leads to methylated members of the nocazine/XR334 (e.g. XR334) family and the other catalyzes DKP N-methylation of cyclo(L-tryptophanyl-L-tryptophanyl) (cWW) to yield dimethyl-cyclo-Trp-Trp (Me2-cWW)
-
evolution
-
methyltransferase homologues are commonly encoded within putative CDPS gene clusters, yet methyltransferases from only two of these clusters have been characterized to date. One leads to methylated members of the nocazine/XR334 (e.g. XR334) family and the other catalyzes DKP N-methylation of cyclo(L-tryptophanyl-L-tryptophanyl) (cWW) to yield dimethyl-cyclo-Trp-Trp (Me2-cWW)
-
evolution
-
methyltransferase homologues are commonly encoded within putative CDPS gene clusters, yet methyltransferases from only two of these clusters have been characterized to date. One leads to methylated members of the nocazine/XR334 (e.g. XR334) family and the other catalyzes DKP N-methylation of cyclo(L-tryptophanyl-L-tryptophanyl) (cWW) to yield dimethyl-cyclo-Trp-Trp (Me2-cWW)
-
evolution
Rickettsiella grylli ATCC 700358
-
CDPSs fall into two subfamilies, NYH and XYP, characterized by the presence of specific sequence signatures. Comparison of the XYP and NYH enzymes shows that the two subfamilies mainly differ in the first half of their Rossmann fold. The XYP and NYH motifs correspond to two structural solutions to facilitate the reactivity of the catalytic serine residue. The CDPS from Rickettsiella grylli belongs to the XYP subfamily
-
evolution
-
methyltransferase homologues are commonly encoded within putative CDPS gene clusters, yet methyltransferases from only two of these clusters have been characterized to date. One leads to methylated members of the nocazine/XR334 (e.g. XR334) family and the other catalyzes DKP N-methylation of cyclo(L-tryptophanyl-L-tryptophanyl) (cWW) to yield dimethyl-cyclo-Trp-Trp (Me2-cWW)
-
evolution
-
methyltransferase homologues are commonly encoded within putative CDPS gene clusters, yet methyltransferases from only two of these clusters have been characterized to date. One leads to methylated members of the nocazine/XR334 (e.g. XR334) family and the other catalyzes DKP N-methylation of cyclo(L-tryptophanyl-L-tryptophanyl) (cWW) to yield dimethyl-cyclo-Trp-Trp (Me2-cWW)
-
evolution
-
methyltransferase homologues are commonly encoded within putative CDPS gene clusters, yet methyltransferases from only two of these clusters have been characterized to date. One leads to methylated members of the nocazine/XR334 (e.g. XR334) family and the other catalyzes DKP N-methylation of cyclo(L-tryptophanyl-L-tryptophanyl) (cWW) to yield dimethyl-cyclo-Trp-Trp (Me2-cWW)
-
evolution
-
methyltransferase homologues are commonly encoded within putative CDPS gene clusters, yet methyltransferases from only two of these clusters have been characterized to date. One leads to methylated members of the nocazine/XR334 (e.g. XR334) family and the other catalyzes DKP N-methylation of cyclo(L-tryptophanyl-L-tryptophanyl) (cWW) to yield dimethyl-cyclo-Trp-Trp (Me2-cWW)
-
metabolism
comparison of different CDPS-containing biosynthetic pathways, enzyme AlbC is involved in the albonoursin biosynthetic pathway, overview. Assembly of the cyclo-Phe-Leu precursor of albonoursin is catalyzed by CDPS AlbC, which also yields a variety of other cyclic dipeptides as minor products
metabolism
-
comparison of different CDPS-containing biosynthetic pathways, enzyme BcmA is involved in the bicyclomycin biosynthetic pathway, overview. The proposed bicyclomycin (i.e. (1S,6R)-6-hydroxy-5-methylidene-1-[(2S)-1,2,3-trihydroxy-2-methylpropyl]-2-oxa-7,9-diazabicyclo[4.2.2]decane-8,10-dione) biosynthetic pathway features a cascade of oxidative transformations
metabolism
comparison of different CDPS-containing biosynthetic pathways, the enzyme encoded by gene ndas_1148 is involved in the XR334 (i.e. (3Z,6Z)-3-benzylidene-6-[(4-methoxyphenyl)methylidene]piperazine-2,5-dione) biosynthetic pathway, overview
metabolism
-
various cyclodipeptide-tailoring enzymes are found in 2,5-diketopiperazine (2,5-DKP) biosynthetic pathways
metabolism
-
comparison of different CDPS-containing biosynthetic pathways, the enzyme encoded by gene ndas_1148 is involved in the XR334 (i.e. (3Z,6Z)-3-benzylidene-6-[(4-methoxyphenyl)methylidene]piperazine-2,5-dione) biosynthetic pathway, overview
-
metabolism
-
comparison of different CDPS-containing biosynthetic pathways, the enzyme encoded by gene ndas_1148 is involved in the XR334 (i.e. (3Z,6Z)-3-benzylidene-6-[(4-methoxyphenyl)methylidene]piperazine-2,5-dione) biosynthetic pathway, overview
-
metabolism
-
comparison of different CDPS-containing biosynthetic pathways, the enzyme encoded by gene ndas_1148 is involved in the XR334 (i.e. (3Z,6Z)-3-benzylidene-6-[(4-methoxyphenyl)methylidene]piperazine-2,5-dione) biosynthetic pathway, overview
-
metabolism
-
comparison of different CDPS-containing biosynthetic pathways, the enzyme encoded by gene ndas_1148 is involved in the XR334 (i.e. (3Z,6Z)-3-benzylidene-6-[(4-methoxyphenyl)methylidene]piperazine-2,5-dione) biosynthetic pathway, overview
-
metabolism
-
comparison of different CDPS-containing biosynthetic pathways, the enzyme encoded by gene ndas_1148 is involved in the XR334 (i.e. (3Z,6Z)-3-benzylidene-6-[(4-methoxyphenyl)methylidene]piperazine-2,5-dione) biosynthetic pathway, overview
-
metabolism
-
comparison of different CDPS-containing biosynthetic pathways, the enzyme encoded by gene ndas_1148 is involved in the XR334 (i.e. (3Z,6Z)-3-benzylidene-6-[(4-methoxyphenyl)methylidene]piperazine-2,5-dione) biosynthetic pathway, overview
-
metabolism
-
comparison of different CDPS-containing biosynthetic pathways, the enzyme encoded by gene ndas_1148 is involved in the XR334 (i.e. (3Z,6Z)-3-benzylidene-6-[(4-methoxyphenyl)methylidene]piperazine-2,5-dione) biosynthetic pathway, overview
-
metabolism
-
comparison of different CDPS-containing biosynthetic pathways, the enzyme encoded by gene ndas_1148 is involved in the XR334 (i.e. (3Z,6Z)-3-benzylidene-6-[(4-methoxyphenyl)methylidene]piperazine-2,5-dione) biosynthetic pathway, overview
-
physiological function
-
cyclodipeptide synthases (CDPSs) are recognized catalysts of 2,5-diketopiperazine (DKP) assembly, employing two aminoacyl-tRNAs (aa-tRNAs) as substrates. Representative 2,5-diketopiperazine (DKP) natural products and bioactivities, overview
physiological function
cyclodipeptide synthases (CDPSs) are recognized catalysts of 2,5-diketopiperazine (DKP) assembly, employing two aminoacyl-tRNAs (aa-tRNAs) as substrates. Representative 2,5-diketopiperazine (DKP) natural products and bioactivities, overview
physiological function
cyclodipeptide synthases (CDPSs) are recognized catalysts of 2,5-diketopiperazine (DKP) assembly, employing two aminoacyl-tRNAs (aa-tRNAs) as substrates. Representative 2,5-diketopiperazine (DKP) natural products and bioactivities, overview
physiological function
-
cyclodipeptide synthases incorporate non-canonical amino acids into 2,5-diketopiperazines through a ping-pong catalytic mechanism for the stereospecific formation of various cyclodipeptides [cyclo(l-AA1-l-AA2), with AA1 and AA2 corresponding to the two incorporated aminoacyl moieties]
physiological function
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cyclodipeptide synthases (CDPSs) are recognized catalysts of 2,5-diketopiperazine (DKP) assembly, employing two aminoacyl-tRNAs (aa-tRNAs) as substrates. Representative 2,5-diketopiperazine (DKP) natural products and bioactivities, overview
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physiological function
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cyclodipeptide synthases (CDPSs) are recognized catalysts of 2,5-diketopiperazine (DKP) assembly, employing two aminoacyl-tRNAs (aa-tRNAs) as substrates. Representative 2,5-diketopiperazine (DKP) natural products and bioactivities, overview
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physiological function
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cyclodipeptide synthases (CDPSs) are recognized catalysts of 2,5-diketopiperazine (DKP) assembly, employing two aminoacyl-tRNAs (aa-tRNAs) as substrates. Representative 2,5-diketopiperazine (DKP) natural products and bioactivities, overview
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physiological function
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cyclodipeptide synthases (CDPSs) are recognized catalysts of 2,5-diketopiperazine (DKP) assembly, employing two aminoacyl-tRNAs (aa-tRNAs) as substrates. Representative 2,5-diketopiperazine (DKP) natural products and bioactivities, overview
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physiological function
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cyclodipeptide synthases (CDPSs) are recognized catalysts of 2,5-diketopiperazine (DKP) assembly, employing two aminoacyl-tRNAs (aa-tRNAs) as substrates. Representative 2,5-diketopiperazine (DKP) natural products and bioactivities, overview
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physiological function
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cyclodipeptide synthases (CDPSs) are recognized catalysts of 2,5-diketopiperazine (DKP) assembly, employing two aminoacyl-tRNAs (aa-tRNAs) as substrates. Representative 2,5-diketopiperazine (DKP) natural products and bioactivities, overview
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physiological function
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cyclodipeptide synthases (CDPSs) are recognized catalysts of 2,5-diketopiperazine (DKP) assembly, employing two aminoacyl-tRNAs (aa-tRNAs) as substrates. Representative 2,5-diketopiperazine (DKP) natural products and bioactivities, overview
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physiological function
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cyclodipeptide synthases (CDPSs) are recognized catalysts of 2,5-diketopiperazine (DKP) assembly, employing two aminoacyl-tRNAs (aa-tRNAs) as substrates. Representative 2,5-diketopiperazine (DKP) natural products and bioactivities, overview
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additional information
analysis of the cyclization reaction in the cyclodipeptide synthase AlbC using QM/MM methods and free energy simulations, overview. The catalytic Y202 residue is in its neutral protonated form, and thus, is not likely to serve as a general base during the reaction. The reaction relies on the conserved residue Y202 serving as a proton relay, and the direct proton transfer from the amino group to S37 of AlbC is unlikely. Calculations reveal that the hydroxyl group of tyrosine is more suitable for the proton transfer than hydroxyl groups of other amino acids, such as serine and threonine. Residues E182, N40, Y178 and H203 maintain the correct conformation of the dipeptide needed for the cyclization reaction. The mechanism discovered relies on the amino groups conserved among the entire CDPS family and, thus is expected to be universal among CDPSs. Active site pocket structure of the AlbC cyclodipeptide synthase, overview. Residues N40 and H203 are important for the function of AlbC. Residue Y202 is strictly conserved and suggested to play a key role during the cyclization step of the reaction, Y202 is involved in the cyclization process. Analysis of the cyclization reaction catalyzed by AlbC using a set of simulation techniques, including free energy calculations using molecular mechanics (MM) to establish which group of the complex might participate as proton acceptor/donor, DFT hybrid quantum chemical (QM)/MM potentials together with reaction-path-finding algorithms to test possible mechanistic pathways, and QM/MM free energy calculations to determine reaction barriers, detailed overview
additional information
CDPSs structure comparisons, comparison of the XYP and NYH enzymes shows that the two subfamilies mainly differ in the first half of their Rossmann fold, overview. The XYP and the NYH architectures appear as two solutions to stabilize Y202 and facilitate the reactivity of the catalytic S37. Despite these differences, the key catalytic residues (S37, Y202, Y178 and E182, AlbC numbering) are conserved in all CDPSs and have a same location in the catalytic centre of the enzymes. Residues belonging to the signature sequences play parallel roles in the two subfamilies, contributing to the positioning of the catalytic serine and of the crucial Y202 residue. The mode of action of the signature residues however differs, with a more complex network of hydrogen bonds in NYH enzymes. Notably, the signature residues are located in the two catalytic loops at the switch point between the two halves of the Rossmann fold
additional information
CDPSs structure comparisons, comparison of the XYP and NYH enzymes shows that the two subfamilies mainly differ in the first half of their Rossmann fold, overview. The XYP and the NYH architectures appear as two solutions to stabilize Y202 and facilitate the reactivity of the catalytic S37. The XYP and the NYH architectures appear as two solutions to stabilize Y202 and facilitate the reactivity of the catalytic S37. The XYP and the NYH architectures appear as two solutions to stabilize Y202 and facilitate the reactivity of the catalytic S37. Despite these differences, the key catalytic residues (S37, Y202, Y178 and E182, AlbC numbering) are conserved in all CDPSs and have a same location in the catalytic centre of the enzymes. Residues belonging to the signature sequences play parallel roles in the two subfamilies, contributing to the positioning of the catalytic serine and of the crucial Y202 residue. The mode of action of the signature residues however differs, with a more complex network of hydrogen bonds in NYH enzymes. Notably, the signature residues are located in the two catalytic loops at the switch point between the two halves of the Rossmann fold
additional information
CDPSs structure comparisons, comparison of the XYP and NYH enzymes shows that the two subfamilies mainly differ in the first half of their Rossmann fold, overview. The XYP and the NYH architectures appear as two solutions to stabilize Y202 and facilitate the reactivity of the catalytic S37. The XYP and the NYH architectures appear as two solutions to stabilize Y202 and facilitate the reactivity of the catalytic S37. The XYP and the NYH architectures appear as two solutions to stabilize Y202 and facilitate the reactivity of the catalytic S37. Despite these differences, the key catalytic residues (S37, Y202, Y178 and E182, AlbC numbering) are conserved in all CDPSs and have a same location in the catalytic centre of the enzymes. Residues belonging to the signature sequences play parallel roles in the two subfamilies, contributing to the positioning of the catalytic serine and of the crucial Y202 residue. The mode of action of the signature residues however differs, with a more complex network of hydrogen bonds in NYH enzymes. Notably, the signature residues are located in the two catalytic loops at the switch point between the two halves of the Rossmann fold
additional information
CDPSs structure comparisons, comparison of the XYP and NYH enzymes shows that the two subfamilies mainly differ in the first half of their Rossmann fold, overview. The XYP and the NYH architectures appear as two solutions to stabilize Y202 and facilitate the reactivity of the catalytic S37. The XYP and the NYH architectures appear as two solutions to stabilize Y202 and facilitate the reactivity of the catalytic S37. The XYP and the NYH architectures appear as two solutions to stabilize Y202 and facilitate the reactivity of the catalytic S37. Despite these differences, the key catalytic residues (S37, Y202, Y178 and E182, AlbC numbering) are conserved in all CDPSs and have a same location in the catalytic centre of the enzymes. Residues belonging to the signature sequences play parallel roles in the two subfamilies, contributing to the positioning of the catalytic serine and of the crucial Y202 residue. The mode of action of the signature residues however differs, with a more complex network of hydrogen bonds in NYH enzymes. Notably, the signature residues are located in the two catalytic loops at the switch point between the two halves of the Rossmann fold
additional information
structural studies on the CDPS AlbChave lead to the identification of the two pockets P1 and P2 and show that these pockets are bordered by eight and seven residues, respectively. Cyclodipeptides produced by CDPSs, general overview
additional information
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the CDPS adopts a common architecture with a monomer built around a Rossmann fold domain that displays structural similarity to the catalytic domain of the two class Ic aminoacyl-tRNA synthetases (aaRSs), TyrRS and TrpRS. It contains a deep surface-accessible pocket P1, the location of which corresponds to that of the aminoacyl-binding pocket of the two aaRSs. Catalytic mechanism, overview
additional information
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the CDPS catalytic mechanism entails initial covalent tethering of the aminoacyl moiety from the first aa-tRNA substrate onto a conserved active site serine (Ser) residue. Nucleophilic attack of the amino nitrogen on the carbonyl carbon from the second aa-tRNA substrate yields the first peptide bond. The resulting enzyme-linked dipeptidyl intermediate then undergoes intramolecular peptide bond formation to yield the DKP group with concomitant release from the active site. The two aa-tRNA substrates bind at different sites of the CDPS
additional information
the CDPS catalytic mechanism entails initial covalent tethering of the aminoacyl moiety from the first aa-tRNA substrate onto a conserved active site serine (Ser) residue. Nucleophilic attack of the amino nitrogen on the carbonyl carbon from the second aa-tRNA substrate yields the first peptide bond. The resulting enzyme-linked dipeptidyl intermediate then undergoes intramolecular peptide bond formation to yield the DKP group with concomitant release from the active site. The two aa-tRNA substrates bind at different sites of the CDPS
additional information
the CDPS catalytic mechanism entails initial covalent tethering of the aminoacyl moiety from the first aa-tRNA substrate onto a conserved active site serine (Ser) residue. Nucleophilic attack of the amino nitrogen on the carbonyl carbon from the second aa-tRNA substrate yields the first peptide bond. The resulting enzyme-linked dipeptidyl intermediate then undergoes intramolecular peptide bond formation to yield the DKP group with concomitant release from the active site. The two aa-tRNA substrates bind at different sites of the CDPS
additional information
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CDPSs structure comparisons, comparison of the XYP and NYH enzymes shows that the two subfamilies mainly differ in the first half of their Rossmann fold, overview. The XYP and the NYH architectures appear as two solutions to stabilize Y202 and facilitate the reactivity of the catalytic S37. The XYP and the NYH architectures appear as two solutions to stabilize Y202 and facilitate the reactivity of the catalytic S37. The XYP and the NYH architectures appear as two solutions to stabilize Y202 and facilitate the reactivity of the catalytic S37. Despite these differences, the key catalytic residues (S37, Y202, Y178 and E182, AlbC numbering) are conserved in all CDPSs and have a same location in the catalytic centre of the enzymes. Residues belonging to the signature sequences play parallel roles in the two subfamilies, contributing to the positioning of the catalytic serine and of the crucial Y202 residue. The mode of action of the signature residues however differs, with a more complex network of hydrogen bonds in NYH enzymes. Notably, the signature residues are located in the two catalytic loops at the switch point between the two halves of the Rossmann fold
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additional information
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the CDPS catalytic mechanism entails initial covalent tethering of the aminoacyl moiety from the first aa-tRNA substrate onto a conserved active site serine (Ser) residue. Nucleophilic attack of the amino nitrogen on the carbonyl carbon from the second aa-tRNA substrate yields the first peptide bond. The resulting enzyme-linked dipeptidyl intermediate then undergoes intramolecular peptide bond formation to yield the DKP group with concomitant release from the active site. The two aa-tRNA substrates bind at different sites of the CDPS
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additional information
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the CDPS catalytic mechanism entails initial covalent tethering of the aminoacyl moiety from the first aa-tRNA substrate onto a conserved active site serine (Ser) residue. Nucleophilic attack of the amino nitrogen on the carbonyl carbon from the second aa-tRNA substrate yields the first peptide bond. The resulting enzyme-linked dipeptidyl intermediate then undergoes intramolecular peptide bond formation to yield the DKP group with concomitant release from the active site. The two aa-tRNA substrates bind at different sites of the CDPS
-
additional information
-
the CDPS catalytic mechanism entails initial covalent tethering of the aminoacyl moiety from the first aa-tRNA substrate onto a conserved active site serine (Ser) residue. Nucleophilic attack of the amino nitrogen on the carbonyl carbon from the second aa-tRNA substrate yields the first peptide bond. The resulting enzyme-linked dipeptidyl intermediate then undergoes intramolecular peptide bond formation to yield the DKP group with concomitant release from the active site. The two aa-tRNA substrates bind at different sites of the CDPS
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additional information
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the CDPS catalytic mechanism entails initial covalent tethering of the aminoacyl moiety from the first aa-tRNA substrate onto a conserved active site serine (Ser) residue. Nucleophilic attack of the amino nitrogen on the carbonyl carbon from the second aa-tRNA substrate yields the first peptide bond. The resulting enzyme-linked dipeptidyl intermediate then undergoes intramolecular peptide bond formation to yield the DKP group with concomitant release from the active site. The two aa-tRNA substrates bind at different sites of the CDPS
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additional information
Rickettsiella grylli ATCC 700358
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CDPSs structure comparisons, comparison of the XYP and NYH enzymes shows that the two subfamilies mainly differ in the first half of their Rossmann fold, overview. The XYP and the NYH architectures appear as two solutions to stabilize Y202 and facilitate the reactivity of the catalytic S37. The XYP and the NYH architectures appear as two solutions to stabilize Y202 and facilitate the reactivity of the catalytic S37. The XYP and the NYH architectures appear as two solutions to stabilize Y202 and facilitate the reactivity of the catalytic S37. Despite these differences, the key catalytic residues (S37, Y202, Y178 and E182, AlbC numbering) are conserved in all CDPSs and have a same location in the catalytic centre of the enzymes. Residues belonging to the signature sequences play parallel roles in the two subfamilies, contributing to the positioning of the catalytic serine and of the crucial Y202 residue. The mode of action of the signature residues however differs, with a more complex network of hydrogen bonds in NYH enzymes. Notably, the signature residues are located in the two catalytic loops at the switch point between the two halves of the Rossmann fold
-
additional information
-
the CDPS catalytic mechanism entails initial covalent tethering of the aminoacyl moiety from the first aa-tRNA substrate onto a conserved active site serine (Ser) residue. Nucleophilic attack of the amino nitrogen on the carbonyl carbon from the second aa-tRNA substrate yields the first peptide bond. The resulting enzyme-linked dipeptidyl intermediate then undergoes intramolecular peptide bond formation to yield the DKP group with concomitant release from the active site. The two aa-tRNA substrates bind at different sites of the CDPS
-
additional information
-
the CDPS catalytic mechanism entails initial covalent tethering of the aminoacyl moiety from the first aa-tRNA substrate onto a conserved active site serine (Ser) residue. Nucleophilic attack of the amino nitrogen on the carbonyl carbon from the second aa-tRNA substrate yields the first peptide bond. The resulting enzyme-linked dipeptidyl intermediate then undergoes intramolecular peptide bond formation to yield the DKP group with concomitant release from the active site. The two aa-tRNA substrates bind at different sites of the CDPS
-
additional information
-
the CDPS catalytic mechanism entails initial covalent tethering of the aminoacyl moiety from the first aa-tRNA substrate onto a conserved active site serine (Ser) residue. Nucleophilic attack of the amino nitrogen on the carbonyl carbon from the second aa-tRNA substrate yields the first peptide bond. The resulting enzyme-linked dipeptidyl intermediate then undergoes intramolecular peptide bond formation to yield the DKP group with concomitant release from the active site. The two aa-tRNA substrates bind at different sites of the CDPS
-
additional information
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the CDPS catalytic mechanism entails initial covalent tethering of the aminoacyl moiety from the first aa-tRNA substrate onto a conserved active site serine (Ser) residue. Nucleophilic attack of the amino nitrogen on the carbonyl carbon from the second aa-tRNA substrate yields the first peptide bond. The resulting enzyme-linked dipeptidyl intermediate then undergoes intramolecular peptide bond formation to yield the DKP group with concomitant release from the active site. The two aa-tRNA substrates bind at different sites of the CDPS
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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). D7B1W8_NOCDD
Nocardiopsis dassonvillei (strain ATCC 23218 / DSM 43111 / CIP 107115 / JCM 7437 / KCTC 9190 / NBRC 14626 / NCTC 10488 / NRRL B-5397 / IMRU 509)
244
0
26997
TrEMBL
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PDB
SCOP
CATH
UNIPROT
ORGANISM
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CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
purified recombinant enzyme, crystallization from 11% PEG 3350, 0.1 M HEPES, pH 7.5, and 0.2 M L-Pro, X-ray difffraction structure determination and analysis at 3.06 A resolution
purified recombinant enzyme, crystallization from 22% PEG 3350, 0.2 M tri-ammonium citrate, pH 7.0, X-ray difffraction structure determination and analysis at 3.18 A resolution
purified recombinant enzyme, crystallization from 15.2% PEG 3350, 0.1 M potassium fluoride, X-ray difffraction structure determination and analysis at 1.99 A resolution
hanging drop vapor diffusion method, using 10% (w/v) PEG8000, 50 mM KCl, 50 mM sodium cacodylate, pH 6.0
to 1.9 A resolution, monomer that presents a compact alpha/beta structure. It is composed of a central beta-sheet with five parallel beta strands surrounded by ten alpha helices. AlbC contains a deep pocket, highly conserved among cyclodipeptide synthases. This pocket accommodates the aminoacyl moiety of the aa-tRNA substrate
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PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
E182D
mutation in putative catalytic pocket, about 1% of wild-type activity
G35A
mutation in putative catalytic pocket, about 5% of wild-type activity
S37C
mutation in putative catalytic pocket, about 5% of wild-type activity
Y178F
mutation in putative catalytic pocket, about 10% of wild-type activity
Y202F
Y202F
mutation in putative catalytic pocket, about 15% of wild-type activity
Y202F
the mutation does not affect the formation of the aminoacyl enzyme intermediate5, but leads to the accumulation of the covalent dipeptidyl enzyme intermediate, which is not observed with the wild-type enzyme
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PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
recombinant enzyme from Escherichia coli strain BL21AI
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CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
gene albC, recombinant expression in Escherichia coli strain BL21AI, subcloning in Escherichia coli strain DH5alpha
gene albC, sequence comparisons and phylogenetic analysis, recombinant expression of codon-optimized gene in Escherichia coli strain M15
gene bmcA, recombinant expression of the bcm cluster in heterologous host Streptomyces coelicolor, resulting in production of bicyclomycin
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gene NCTC11370_02388, recombinant expression in Escherichia coli strain BL21AI, subcloning in Escherichia coli strain DH5alpha
gene O3I_025450, recombinant expression in Escherichia coli strain BL21AI, subcloning in Escherichia coli strain DH5alpha
gene RICGR_0139, recombinant expression in Escherichia coli strain BL21AI, subcloning in Escherichia coli strain DH5alpha
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