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Information on EC 2.3.2.22 - cyclo(L-leucyl-L-leucyl) synthase
for references in articles please use BRENDA:EC2.3.2.22
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EC Tree 2 Transferases
2.3 Acyltransferases
2.3.2 Aminoacyltransferases
2.3.2.22 cyclo(L-leucyl-L-leucyl) synthase
IUBMB Comments
The reaction proceeds following a ping-pong mechanism forming a covalent intermediate between an active site serine and the first L-leucine residue . The proteins from bacteria of the genus Bacillus also form small amounts of cyclo(L-phenylalanyl-L-leucyl) and cyclo(L-leucyl-L-methionyl) .
The expected taxonomic range for this enzyme is: Bacteria, Eukaryota
showSynonyms
BcmA, CDPS, cLL synthase, cyclo(L-leucyl-L-leucyl) synthase, cyclodileucine synthase, cyclodipeptide synthase, pSHaeC06, Shae-CDPS, YvmC, more
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SYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
CDPS
cLL synthase
cyclo(L-leucyl-L-leucyl) synthase
cyclodileucine synthase
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cyclodipeptide synthase
pSHaeC06
Shae-CDPS
YvmC
cLL synthase
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YvmC
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REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
2 L-leucyl-tRNALeu = 2 tRNALeu + cyclo(L-leucyl-L-leucyl)
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2 L-leucyl-tRNALeu = 2 tRNALeu + cyclo(L-leucyl-L-leucyl)
sequential catalytic mechanism, with the successive attachment of two leucine residues on the enzyme via a conserved serine residue
2 L-leucyl-tRNALeu = 2 tRNALeu + cyclo(L-leucyl-L-leucyl)
sequential catalytic mechanism, with the successive attachment of two leucine residues on the enzyme via a conserved serine residue
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PATHWAY SOURCE
PATHWAYS
MetaCyc
pulcherrimin biosynthesis
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SYSTEMATIC NAME
IUBMB Comments
L-leucyl-tRNALeu:L-leucyl-tRNALeu leucyltransferase (cyclizing)
The reaction proceeds following a ping-pong mechanism forming a covalent intermediate between an active site serine and the first L-leucine residue [2]. The proteins from bacteria of the genus Bacillus also form small amounts of cyclo(L-phenylalanyl-L-leucyl) and cyclo(L-leucyl-L-methionyl) [1].
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SUBSTRATE
PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
LITERATURE
COMMENTARY
Reversibility
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
2 cyclo-penta-alanyl-tRNALeu
2 tRNALeu + cyclo(L-cyclo-penta-alanyl-L-cyclo-penta-alanyl)
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Substrates: -
Products: -
Products: -
?
2 L-isoleucyl-tRNAIle
2 tRNAIle + cyclo(L-isoleucyl-L-isoleucyl)
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Substrates: -
Products: -
Products: -
?
2 L-methionyl-tRNAMet
2 tRNAMet + cyclo(L-methionyl-L-methionyl)
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Substrates: -
Products: -
Products: -
?
2 N-dinitrobenzyl-L-Leu
2 dinitrobenzol + cyclo(L-leucyl-L-leucyl)
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Substrates: poor substrate
Products: -
Products: -
?
2 trifluoroleucyl-tRNALeu
2 tRNALeu + cyclo(L-trifluoroleucyl-L-trifluoroleucyl)
-
Substrates: -
Products: -
Products: -
?
L-isoleucyl-tRNAIle + L-leucyl-tRNALeu
tRNAIle + tRNALeu + cyclo(L-isoleucyl-L-leucyl)
Substrates: -
Products: -
Products: -
?
L-leucyl-tRNALeu + L-alanyl-tRNAAla
tRNALeu + tRNAAla + cyclo(L-leucyl-L-alanyl)
Substrates: -
Products: -
Products: -
?
L-leucyl-tRNALeu + L-valyl-tRNAVal
tRNALeu + tRNAVal + cyclo(L-leucyl-L-valyl)
Substrates: -
Products: -
Products: -
?
2 L-leucyl-tRNALeu
2 tRNALeu + cyclo(L-leucyl-L-leucyl)
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Substrates: -
Products: -
Products: -
?
2 L-leucyl-tRNALeu
2 tRNALeu + cyclo(L-leucyl-L-leucyl)
Substrates: -
Products: -
Products: -
?
2 L-leucyl-tRNALeu
2 tRNALeu + cyclo(L-leucyl-L-leucyl)
Substrates: -
Products: -
Products: -
?
2 L-leucyl-tRNALeu
2 tRNALeu + cyclo(L-leucyl-L-leucyl)
-
Substrates: -
Products: -
Products: -
?
2 L-leucyl-tRNALeu
2 tRNALeu + cyclo(L-leucyl-L-leucyl)
Substrates: -
Products: -
Products: -
?
L-leucyl-tRNALeu + L-leucyl-tRNALeu
tRNALeu + tRNALeu + cyclo(L-leucyl-L-leucyl)
Substrates: -
Products: -
Products: -
?
L-leucyl-tRNALeu + L-leucyl-tRNALeu
tRNALeu + tRNALeu + cyclo(L-leucyl-L-leucyl)
Bacillus spizizenii ATCC 23059
Substrates: -
Products: -
Products: -
?
L-leucyl-tRNALeu + L-leucyl-tRNALeu
tRNALeu + tRNALeu + cyclo(L-leucyl-L-leucyl)
Bacillus spizizenii NRRL B-14472
Substrates: -
Products: -
Products: -
?
L-leucyl-tRNALeu + L-leucyl-tRNALeu
tRNALeu + tRNALeu + cyclo(L-leucyl-L-leucyl)
Substrates: -
Products: -
Products: -
?
additional information
?
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Substrates: cyclodipeptide synthases (CDPSs) use two aminoacyl-tRNAs to catalyze the formation of two peptide bonds leading to cyclodipeptides. Catalytic mechanism, overview
Products: -
Products: -
?
additional information
?
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Substrates: cyclodipeptide synthases (CDPSs) use two aminoacyl-tRNAs to catalyze the formation of two peptide bonds leading to cyclodipeptides. Catalytic mechanism, overview
Products: -
Products: -
?
additional information
?
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Substrates: cyclodipeptide synthases (CDPSs) use two aminoacyl-tRNAs to catalyze the formation of two peptide bonds leading to cyclodipeptides. Catalytic mechanism, overview
Products: -
Products: -
?
additional information
?
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Substrates: cyclodipeptide synthases (CDPSs) use two aminoacyl-tRNAs to catalyze the formation of two peptide bonds leading to cyclodipeptides. Catalytic mechanism, overview
Products: -
Products: -
?
additional information
?
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Substrates: cyclodipeptide synthases (CDPSs) use two aminoacyl-tRNAs to catalyze the formation of two peptide bonds leading to cyclodipeptides. Catalytic mechanism, overview
Products: -
Products: -
?
additional information
?
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Substrates: cyclodipeptide synthases (CDPSs) use two aminoacyl-tRNAs to catalyze the formation of two peptide bonds leading to cyclodipeptides. Catalytic mechanism, overview
Products: -
Products: -
?
additional information
?
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Substrates: cyclodipeptide synthases (CDPSs) use two aminoacyl-tRNAs to catalyze the formation of two peptide bonds leading to cyclodipeptides. Catalytic mechanism, overview
Products: -
Products: -
?
additional information
?
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Substrates: cyclodipeptide synthases (CDPSs) use two aminoacyl-tRNAs to catalyze the formation of two peptide bonds leading to cyclodipeptides. Catalytic mechanism, overview
Products: -
Products: -
?
additional information
?
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Substrates: the CDPS YvmC catalyzes formation of major product cyclo(L-leucyl-L-leucyl) as well as minor cyclic dipeptide products containing one leucine residue
Products: -
Products: -
?
additional information
?
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Bacillus spizizenii ATCC 23059
Substrates: the CDPS YvmC catalyzes formation of major product cyclo(L-leucyl-L-leucyl) as well as minor cyclic dipeptide products containing one leucine residue
Products: -
Products: -
?
additional information
?
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Bacillus spizizenii NRRL B-14472
Substrates: the CDPS YvmC catalyzes formation of major product cyclo(L-leucyl-L-leucyl) as well as minor cyclic dipeptide products containing one leucine residue
Products: -
Products: -
?
additional information
?
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Substrates: the CDPS YvmC catalyzes formation of major product cyclo(L-leucyl-L-leucyl) as well as minor cyclic dipeptide products containing one leucine residue
Products: -
Products: -
?
additional information
?
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Substrates: leu-tRNA isoacceptors from Bacillus thermoamylovorans (TTA, TTG, CTA, CTC, CTG) all produce similar quantities of product. L-valyl-tRNAVal is not accepted
Products: -
Products: -
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additional information
?
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Substrates: cyclodipeptide synthases (CDPSs) use two aminoacyl-tRNAs to catalyze the formation of two peptide bonds leading to cyclodipeptides
Products: -
Products: -
?
additional information
?
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Substrates: cyclodipeptide synthases (CDPSs) use two aminoacyl-tRNAs to catalyze the formation of two peptide bonds leading to cyclodipeptides
Products: -
Products: -
?
additional information
?
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Substrates: 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-phenylalanyl-L-leucyl) synthase, EC 2.3.2.20
Products: -
Products: -
?
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NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
LITERATURE
COMMENTARY
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
2 L-leucyl-tRNALeu
2 tRNALeu + cyclo(L-leucyl-L-leucyl)
Substrates: -
Products: -
Products: -
?
2 L-leucyl-tRNALeu
2 tRNALeu + cyclo(L-leucyl-L-leucyl)
Substrates: -
Products: -
Products: -
?
L-leucyl-tRNALeu + L-leucyl-tRNALeu
tRNALeu + tRNALeu + cyclo(L-leucyl-L-leucyl)
Substrates: -
Products: -
Products: -
?
L-leucyl-tRNALeu + L-leucyl-tRNALeu
tRNALeu + tRNALeu + cyclo(L-leucyl-L-leucyl)
Bacillus spizizenii ATCC 23059
Substrates: -
Products: -
Products: -
?
L-leucyl-tRNALeu + L-leucyl-tRNALeu
tRNALeu + tRNALeu + cyclo(L-leucyl-L-leucyl)
Bacillus spizizenii NRRL B-14472
Substrates: -
Products: -
Products: -
?
L-leucyl-tRNALeu + L-leucyl-tRNALeu
tRNALeu + tRNALeu + cyclo(L-leucyl-L-leucyl)
Substrates: -
Products: -
Products: -
?
additional information
?
-
Substrates: the CDPS YvmC catalyzes formation of major product cyclo(L-leucyl-L-leucyl) as well as minor cyclic dipeptide products containing one leucine residue
Products: -
Products: -
?
additional information
?
-
Bacillus spizizenii ATCC 23059
Substrates: the CDPS YvmC catalyzes formation of major product cyclo(L-leucyl-L-leucyl) as well as minor cyclic dipeptide products containing one leucine residue
Products: -
Products: -
?
additional information
?
-
Bacillus spizizenii NRRL B-14472
Substrates: the CDPS YvmC catalyzes formation of major product cyclo(L-leucyl-L-leucyl) as well as minor cyclic dipeptide products containing one leucine residue
Products: -
Products: -
?
additional information
?
-
Substrates: the CDPS YvmC catalyzes formation of major product cyclo(L-leucyl-L-leucyl) as well as minor cyclic dipeptide products containing one leucine residue
Products: -
Products: -
?
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ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
Highest Expressing Human Cell Lines
Cell Line LinksPlease wait a moment until the data is sorted. This message will disappear when the data is sorted.
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 Bacillus licheniformis belongs to the NYH 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 Staphylococcus haemolyticus belongs to the TYH subfamily
evolution
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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 Bacillus licheniformis belongs to the NYH subfamily
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evolution
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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 Bacillus licheniformis belongs to the NYH subfamily
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evolution
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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 Bacillus licheniformis belongs to the NYH subfamily
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evolution
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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 Bacillus licheniformis belongs to the NYH subfamily
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evolution
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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 Bacillus licheniformis belongs to the NYH subfamily
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evolution
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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 Bacillus licheniformis belongs to the NYH subfamily
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evolution
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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 Bacillus licheniformis belongs to the NYH subfamily
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evolution
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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 Staphylococcus haemolyticus belongs to the TYH subfamily
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metabolism
in Bacillus subtilis, the enzymes YvmC and CypX are involved in pulcherriminic acid biosynthesis. The cyclodipeptide synthase YvmC utilizes charged leucyl-tRNAs as substrate to catalyze the formation of cyclo-L-leucyl-L-leucyl (cLL). The cytochrome P450 CypX is implicated in the transformation of cLL into pulcherriminic acid. Pulcherriminic acid derived from cyclo-L-leucyl-L-leucyl is excreted and chelates free ferric ions to form the pulcherrimin. Analysis of mechanisms controlling the transcription of the yvmC-cypX operon, overview. The Bacillus subtilis YvmB MarR-like regulator is the major transcription factor controlling yvmC-cypX expression, involvement of YvmB as repressor in the control of yvm-CcypX expression. Expression of yvmB depends on iron availability. Genes yvmBA, yvmC-cypX and yvnB are identified for negative regulation and yisI for positive regulation. A 14-bp palindromic motif constitutes the YvmB binding site. YvmB might not control expression of yisI, whose encoding protein plays a negative role in the regulation of the sporulation initiation pathway. YvmB appears as an additional regulatory element into the cell's decision to grow or sporulate
metabolism
comparison of different CDPS-containing biosynthetic pathways, enzyme YvmC is involved in the pulcherrimin biosynthetic pathway, overview. In Bacillus subtilis, the CDPS YvmC catalyzes formation of major product cyclo(L-leucyl-L-leucyl) as well as minor cyclic dipeptide products containing one leucine residue. The yvmC gene is part of a two gene operon with cypX
metabolism
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in Bacillus subtilis, the enzymes YvmC and CypX are involved in pulcherriminic acid biosynthesis. The cyclodipeptide synthase YvmC utilizes charged leucyl-tRNAs as substrate to catalyze the formation of cyclo-L-leucyl-L-leucyl (cLL). The cytochrome P450 CypX is implicated in the transformation of cLL into pulcherriminic acid. Pulcherriminic acid derived from cyclo-L-leucyl-L-leucyl is excreted and chelates free ferric ions to form the pulcherrimin. Analysis of mechanisms controlling the transcription of the yvmC-cypX operon, overview. The Bacillus subtilis YvmB MarR-like regulator is the major transcription factor controlling yvmC-cypX expression, involvement of YvmB as repressor in the control of yvm-CcypX expression. Expression of yvmB depends on iron availability. Genes yvmBA, yvmC-cypX and yvnB are identified for negative regulation and yisI for positive regulation. A 14-bp palindromic motif constitutes the YvmB binding site. YvmB might not control expression of yisI, whose encoding protein plays a negative role in the regulation of the sporulation initiation pathway. YvmB appears as an additional regulatory element into the cell's decision to grow or sporulate
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metabolism
Bacillus spizizenii ATCC 23059
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comparison of different CDPS-containing biosynthetic pathways, enzyme YvmC is involved in the pulcherrimin biosynthetic pathway, overview. In Bacillus subtilis, the CDPS YvmC catalyzes formation of major product cyclo(L-leucyl-L-leucyl) as well as minor cyclic dipeptide products containing one leucine residue. The yvmC gene is part of a two gene operon with cypX
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metabolism
Bacillus spizizenii NRRL B-14472
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comparison of different CDPS-containing biosynthetic pathways, enzyme YvmC is involved in the pulcherrimin biosynthetic pathway, overview. In Bacillus subtilis, the CDPS YvmC catalyzes formation of major product cyclo(L-leucyl-L-leucyl) as well as minor cyclic dipeptide products containing one leucine residue. The yvmC gene is part of a two gene operon with cypX
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metabolism
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comparison of different CDPS-containing biosynthetic pathways, enzyme YvmC is involved in the pulcherrimin biosynthetic pathway, overview. In Bacillus subtilis, the CDPS YvmC catalyzes formation of major product cyclo(L-leucyl-L-leucyl) as well as minor cyclic dipeptide products containing one leucine residue. The yvmC gene is part of a two gene operon with cypX
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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
Bacillus spizizenii ATCC 23059
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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
Bacillus spizizenii NRRL B-14472
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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
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 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. 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
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
BcmA is a cyclo(L-Ile-L-Leu)-synthesizing CDPS involved in the biosynthesis of the antibiotic bicyclomycin. The residues D161 and K165 in pocket P2 are essential for the activity of BcmA. The conserved residues F158 as well as F210 and S211 in P2 are responsible for determining substrate selectivity
additional information
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the P1 pocket is lined with mainly hydrophobic residues (L29, G31, L61, A63, F112, Phe182, F183, L197). The P2 pocket is shallower and lined with a mixture of residues (R201, W203, K204, D148, S152, A149, R153)
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 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. 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 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. 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
-
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 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. 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
Bacillus spizizenii ATCC 23059
-
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
-
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 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. 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 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. 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 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. 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 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. 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
Bacillus spizizenii NRRL B-14472
-
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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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). CDLS_CORJK
Corynebacterium jeikeium (strain K411)
216
0
24549
Swiss-Prot
other Location (Reliability: 2)
CDLS_STAHJ
Staphylococcus haemolyticus (strain JCSC1435)
234
0
27355
Swiss-Prot
other Location (Reliability: 2)
CDLS_BACLD
Bacillus licheniformis (strain ATCC 14580 / DSM 13 / JCM 2505 / CCUG 7422 / NBRC 12200 / NCIMB 9375 / NCTC 10341 / NRRL NRS-1264 / Gibson 46)
249
0
28550
Swiss-Prot
-
CDLS_PHOLL
Photorhabdus laumondii subsp. laumondii (strain DSM 15139 / CIP 105565 / TT01)
234
0
26893
Swiss-Prot
Secretory Pathway (Reliability: 5)
A0A6M3ZGP1_BACSU
Bacillus subtilis (strain 168)
248
0
28507
TrEMBL
-
A0A8B5YG75_BACLI
249
0
28511
TrEMBL
Secretory Pathway (Reliability: 3)
A0A9Q4EPG1_9BACI
248
0
28451
TrEMBL
Secretory Pathway (Reliability: 2)
A0A9W5PED7_9BACI
281
0
32448
TrEMBL
-
A0AAE2SMN0_BACIU
248
0
28507
TrEMBL
-
E0U3N2_BACSH
Bacillus spizizenii (strain ATCC 23059 / NRRL B-14472 / W23)
248
0
28529
TrEMBL
Secretory Pathway (Reliability: 1)
G4P187_BACS4
Bacillus spizizenii (strain DSM 15029 / JCM 12233 / NBRC 101239 / NRRL B-23049 / TU-B-10)
248
0
28501
TrEMBL
-
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PDB
SCOP
CATH
UNIPROT
ORGANISM
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CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
in the apo form and complexed with substrate mimics, at 1.7-2.4 A resolutions. Data show the presence of an aminoacyl-enzyme reaction intermediate, but not a dipeptide tRNA intermediate. Reaction follows a sequential catalytic mechanism, with the successive attachment of two leucine residues on the enzyme via a conserved serine residue
structure of wild-type and mutant S33A, to 1.69 A and 1.78 A resolution, respectively
-
purified recombinant enzyme, crystallization from 30% PEG 4000, 0.1 M Tris-HCl, pH 8.5, and 0.2 M lithium sulfate monohydrate, X-ray diffraction structure determination and analysis at 2.99 A resolution
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PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
S33C
-
mutation of catalytic residue, facilitates cyclo(L-leucyl-L-leucyl) synthesis compared to wild-type
D161A
2.1- to 2.9fold increase in the total product yield
D161N
2.1- to 2.9fold increase in the total product yield
D161R
2.1- to 2.9fold increase in the total product yield
F158A
mutant is able to produce cVV, cVM, cLM, cIM, cPL, with cAL and cVL as the major products
F210W
mutation results in a reduction in the yields of cAL, cVL, and cIL, an switches the substrate specificity to cyclo(L-Tyr-LLeu) as the major product
K165R
2.1- to 2.9fold increase in the total product yield
S211P
mutant produces a less than 2% of cIL and mainly synthesizes cAL and generates cyclo(L-Pro-L-Leu)
Y162A
complete loss of cyclodipeptide-synthesizing activity
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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 pSHaeC06, recombinant expression in Escherichia coli strain BL21AI, subcloning in Escherichia coli strain DH5alpha
gene yvmC is organized in the yvmC-cypX operon, genetic organization and expression analysis
gene yvmC, recombinant expression in Escherichia coli strain BL21AI, subcloning in Escherichia coli strain DH5alpha
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APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
synthesis
synthesis
cyclodipeptide synthases (CDPSs) use two aminoacyl-tRNAs to catalyze the formation of two peptide bonds leading to cyclodipeptides that can be further used for the synthesis of diketopiperazines
synthesis
cyclodipeptide synthases (CDPSs) use two aminoacyl-tRNAs to catalyze the formation of two peptide bonds leading to cyclodipeptides that can be further used for the synthesis of diketopiperazines
synthesis
-
cyclodipeptide synthases (CDPSs) use two aminoacyl-tRNAs to catalyze the formation of two peptide bonds leading to cyclodipeptides that can be further used for the synthesis of diketopiperazines
-
synthesis
-
cyclodipeptide synthases (CDPSs) use two aminoacyl-tRNAs to catalyze the formation of two peptide bonds leading to cyclodipeptides that can be further used for the synthesis of diketopiperazines
-
synthesis
-
cyclodipeptide synthases (CDPSs) use two aminoacyl-tRNAs to catalyze the formation of two peptide bonds leading to cyclodipeptides that can be further used for the synthesis of diketopiperazines
-
synthesis
-
cyclodipeptide synthases (CDPSs) use two aminoacyl-tRNAs to catalyze the formation of two peptide bonds leading to cyclodipeptides that can be further used for the synthesis of diketopiperazines
-
synthesis
-
cyclodipeptide synthases (CDPSs) use two aminoacyl-tRNAs to catalyze the formation of two peptide bonds leading to cyclodipeptides that can be further used for the synthesis of diketopiperazines
-
synthesis
-
cyclodipeptide synthases (CDPSs) use two aminoacyl-tRNAs to catalyze the formation of two peptide bonds leading to cyclodipeptides that can be further used for the synthesis of diketopiperazines
-
synthesis
-
cyclodipeptide synthases (CDPSs) use two aminoacyl-tRNAs to catalyze the formation of two peptide bonds leading to cyclodipeptides that can be further used for the synthesis of diketopiperazines
-
synthesis
-
cyclodipeptide synthases (CDPSs) use two aminoacyl-tRNAs to catalyze the formation of two peptide bonds leading to cyclodipeptides that can be further used for the synthesis of diketopiperazines
-
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REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Gondry, M.; Sauguet, L.; Belin, P.; Thai, R.; Amouroux, R.; Tellier, C.; Tuphile, K.; Jacquet, M.; Braud, S.; Courcon, M.; Masson, C.; Dubois, S.; Lautru, S.; Lecoq, A.; Hashimoto, S.; Genet, R.; Pernodet, J.L.
Cyclodipeptide synthases are a family of tRNA-dependent peptide bond-forming enzymes
Nat. Chem. Biol.
5
414-420
2009
Streptomyces noursei (Q8GED7), Bacillus subtilis
brenda
Bonnefond, L.; Arai, T.; Sakaguchi, Y.; Suzuki, T.; Ishitani, R.; Nureki, O.
Structural basis for nonribosomal peptide synthesis by an aminoacyl-tRNA synthetase paralog
Proc. Natl. Acad. Sci. USA
108
3912-3917
2011
Bacillus licheniformis (Q65EX3), Bacillus licheniformis ATCC 14580 (Q65EX3)
brenda
Randazzo, P.; Aubert-Frambourg, A.; Guillot, A.; Auger, S.
The MarR-like protein PchR (YvmB) regulates expression of genes involved in pulcherriminic acid biosynthesis and in the initiation of sporulation in Bacillus subtilis
BMC Microbiol.
16
190
2016
Bacillus subtilis (O34351), Bacillus subtilis 168 (O34351)
brenda
Bourgeois, G.; Seguin, J.; Babin, M.; Belin, P.; Moutiez, M.; Mechulam, Y.; Gondry, M.; Schmitt, E.
Structural basis for partition of the cyclodipeptide synthases into two subfamilies
J. Struct. Biol.
203
17-26
2018
Bacillus licheniformis (Q65EX3), Staphylococcus haemolyticus (Q4L2X9), Bacillus licheniformis DSM 13 (Q65EX3), Bacillus licheniformis ATCC 14580 (Q65EX3), Bacillus licheniformis NBRC 12200 (Q65EX3), Bacillus licheniformis JCM 2505 (Q65EX3), Bacillus licheniformis NCIMB 9375 (Q65EX3), Bacillus licheniformis NRRL NRS-1264 (Q65EX3), Bacillus licheniformis Gibson 46 (Q65EX3), Staphylococcus haemolyticus JCSC1435 (Q4L2X9)
brenda
Borgman, P.; Lopez, R.; Lane, A.
The expanding spectrum of diketopiperazine natural product biosynthetic pathways containing cyclodipeptide synthases
Org. Biomol. Chem.
17
2305-2314
2019
Bacillus spizizenii (E0U3N2), Bacillus spizizenii ATCC 23059 (E0U3N2), Bacillus spizizenii NRRL B-14472 (E0U3N2), Bacillus spizizenii W23 (E0U3N2)
brenda
He, J.B.; Ren, Y.; Li, P.; Liu, Y.P.; Pan, H.X.; Huang, L.J.; Wang, J.; Fang, P.; Tang, G.L.
Crystal structure and mutagenesis of an XYP subfamily cyclodipeptide synthase reveal key determinants of enzyme activity and substrate specificity
Biochemistry
63
2969-2976
2024
Streptomyces cinnamoneus (A0A2G1XAZ9)
brenda
Harding, C.J.; Sutherland, E.; Hanna, J.G.; Houston, D.R.; Czekster, C.M.
Bypassing the requirement for aminoacyl-tRNA by a cyclodipeptide synthase enzyme
RSC Chem. Biol.
2
230-240
2021
Caldibacillus thermoamylovorans
brenda
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