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Information on EC 2.5.1.73 - O-phospho-L-seryl-tRNA:Cys-tRNA synthase and Organism(s) Methanocaldococcus jannaschii and UniProt Accession Q59072
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2.5.1.73 O-phospho-L-seryl-tRNA:Cys-tRNA synthaseIUBMB Comments
In organisms like Archaeoglobus fulgidus lacking EC 6.1.1.16 (cysteine---tRNA ligase) for the direct Cys-tRNACys formation, Cys-tRNACys is produced by an indirect pathway, in which EC 6.1.1.27 (O-phosphoseryl-tRNA ligase) ligates O-phosphoserine to tRNACys, and EC 2.5.1.73 converts the produced O-phospho-L-seryl-tRNACys to Cys-tRNACys. The SepRS/SepCysS pathway is the sole route for cysteine biosynthesis in the organism . Methanosarcina mazei can use both pathways, the direct route using EC 6.1.1.16 (cysteine---tRNA ligase) and the indirect pathway with EC 6.1.1.27 (O-phosphoseryl-tRNA ligase) and EC 2.5.1.73 .
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Word Map
- 2.5.1.73
-
cys-trnacys
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methanogen
- archaea
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o-phosphoseryl-trna
- seprs
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cysteinyl-trna
- o-phosphoserine
- sulfur
- cysrs
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trna-dependent
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cysteinyl-trnacys
- jannaschii
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methanocaldococcus
- selenocysteine
- pyridoxal
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methanosarcina
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sec
- aminoacylation
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misacylated
- acetivorans
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auxotrophy
- persulfide
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relay
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sep-trna:sec-trna
- homocysteine
- fulgidus
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isoacceptors
- aminoacyl-trnas
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archaeoglobus
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trna-bound
- maripaludis
The taxonomic range for the selected organisms is: Methanocaldococcus jannaschii
The expected taxonomic range for this enzyme is: Archaea, Bacteria
The expected taxonomic range for this enzyme is: Archaea, Bacteria
Synonyms
sepcyss, sep-trna:cys-trna synthase, sep-trna-cys-trna synthase, 
more
topSYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
Sep-tRNA-Cys-tRNA synthase
both SepRS and SepCysS bind the reaction intermediate Sep-tRNACys tightly, and these two enzymes form a stable binary complex that promotes conversion of the intermediate to the product and sequesters the intermediate from binding to elongation factor EF-1alpha or infiltrating into the ribosome
SepCysS
SYSTEMATIC NAME
IUBMB Comments
O-phospho-L-seryl-tRNACys:hydrogen sulfide 2-aminopropanoate transferase
In organisms like Archaeoglobus fulgidus lacking EC 6.1.1.16 (cysteine---tRNA ligase) for the direct Cys-tRNACys formation, Cys-tRNACys is produced by an indirect pathway, in which EC 6.1.1.27 (O-phosphoseryl-tRNA ligase) ligates O-phosphoserine to tRNACys, and EC 2.5.1.73 converts the produced O-phospho-L-seryl-tRNACys to Cys-tRNACys. The SepRS/SepCysS pathway is the sole route for cysteine biosynthesis in the organism [1]. Methanosarcina mazei can use both pathways, the direct route using EC 6.1.1.16 (cysteine---tRNA ligase) and the indirect pathway with EC 6.1.1.27 (O-phosphoseryl-tRNA ligase) and EC 2.5.1.73 [2].
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
O-phospho-L-seryl-tRNACys + sulfide
L-cysteinyl-tRNACys + phosphate
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-
-
?
O-phospho-L-seryl-tRNACys + sulfide
L-cysteinyl-tRNACys + phosphate
all three highly conserved Cys residues in the enzyme (Cys64, Cys67, and Cys272) are essential for the sulfhydrylation reaction in vivo. Cys64 and Cys67 form a disulfide linkage and carry a sulfane sulfur in a portion of the enzyme. A persulfide group (containing a sulfane sulfur) is the proximal sulfur donor for cysteine biosynthesis
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-
?
O-phospho-L-seryl-tRNACys + sulfide
L-cysteinyl-tRNACys + phosphate
-
the natural sulfur donor is not characterized, the activity of SepCysS provides a means by which both cysteine and selenocysteine can be added to the genetic code, the enzyme is responsible for Cys-tRNACys synthesis together with the O-phosphoseryl-tRNA synthetase in the organism lacking the cysteinyl-tRNACys synthase, EC 6.1.1.16, overview
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-
?
O-phospho-L-seryl-tRNACys + sulfide
L-cysteinyl-tRNACys + phosphate
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sulfide e.g. from Na2S, anaerobic reaction
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-
?
O-phospho-L-seryl-tRNACys + sulfide
L-cysteinyl-tRNACys + phosphate
Methanocaldococcus jannaschii synthesizes Cys-tRNACys by an indirect pathway, whereby O-phosphoseryltRNA synthetase (SepRS) acylates tRNACys with phosphoserine (Sep), and Sep-tRNACys-tRNA synthase (SepCysS) converts the tRNA-bound phosphoserine to cysteine
-
-
?
O-phospho-L-seryl-tRNACys + sulfide
L-cysteinyl-tRNACys + phosphate
Methanocaldococcus jannaschii synthesizes Cys-tRNACys by an indirect pathway, whereby O-phosphoseryltRNA synthetase (SepRS) acylates tRNACys with phosphoserine (Sep), and Sep-tRNACys-tRNA synthase (SepCysS) converts the tRNA-bound phosphoserine to cysteine. O-PhosphoseryltRNA synthetase and Sep-tRNACys-tRNA synthase bind the reaction intermediate O-phospho-L-serine-tRNACys tightly, and these two enzymes form a stable binary complex that promotes conversion of the intermediate to the product and sequesters the intermediate from binding to elongation factor EF-1a or infiltrating into the ribosome
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-
?
additional information
?
-
the highly conserved Cys residues Cys64, Cys67, and Cys272 are essential for the sulfhydrylation reaction in vivo. Cys64 and Cys67 form a disulfide linkage and carry a sulfane sulfur in a portion of the enzyme, suggesting that a persulfide group containing a sulfane sulfur is the proximal sulfur donor for cysteine biosynthesis. The presence of Cys272 increases the amount of sulfane sulfur in the enzyme by 3fold, suggesting that this Cys residue facilitates the generation of the persulfide group. A sulfur relay mechanism recruits both disulfide and persulfide intermediates
-
-
?
additional information
?
-
-
the highly conserved Cys residues Cys64, Cys67, and Cys272 are essential for the sulfhydrylation reaction in vivo. Cys64 and Cys67 form a disulfide linkage and carry a sulfane sulfur in a portion of the enzyme, suggesting that a persulfide group containing a sulfane sulfur is the proximal sulfur donor for cysteine biosynthesis. The presence of Cys272 increases the amount of sulfane sulfur in the enzyme by 3fold, suggesting that this Cys residue facilitates the generation of the persulfide group. A sulfur relay mechanism recruits both disulfide and persulfide intermediates
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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
O-phospho-L-seryl-tRNACys + sulfide
L-cysteinyl-tRNACys + phosphate
-
the natural sulfur donor is not characterized, the activity of SepCysS provides a means by which both cysteine and selenocysteine can be added to the genetic code, the enzyme is responsible for Cys-tRNACys synthesis together with the O-phosphoseryl-tRNA synthetase in the organism lacking the cysteinyl-tRNACys synthase, EC 6.1.1.16, overview
-
-
?
O-phospho-L-seryl-tRNACys + sulfide
L-cysteinyl-tRNACys + phosphate
Methanocaldococcus jannaschii synthesizes Cys-tRNACys by an indirect pathway, whereby O-phosphoseryltRNA synthetase (SepRS) acylates tRNACys with phosphoserine (Sep), and Sep-tRNACys-tRNA synthase (SepCysS) converts the tRNA-bound phosphoserine to cysteine
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-
?
COFACTOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
translation factor SepCysE
essential for methanococcal Cys biosynthesis. Its deletion in Methanococcus maripaludiscauses Cys auxotrophy. SepCysE acts as a scaffold for O-phospho-L-serinetRNA ligase (EC 6.1.1.27) and O-phospho-L-seryl-tRNA:Cys-tRNA synthase to form a stable high-affinity complex for tRNACys causing a 14fold increase in the initial rate of Cys-tRNACys formation
-
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
physiological function
physiological function
wild-type enzyme can complement an Escherichia coli selA knockout strain, which cannot produce active formate dehydrogenase H due to the lack of selenocysteine incorporation
physiological function
the three domains of enhancer SepCysE each bind O-phosphoseryl-tRNA synthetase SepRS, Sep-tRNA:Cys-tRNA synthase SepCysS, and tRNACys, respectively, which mediates the dynamic architecture of the transsulfursome and enables a global long-range channeling of tRNACys between SepRS and SepCysS distant active sites
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
additional information
-
both SepRS and SepCysS are active as a monomer in theSepRSSepCysS binary complex
additional information
both SepRS and SepCysS are active as a monomer in theSepRSSepCysS binary complex
CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
crystal structure of a subcomplex of the transsulfursome with tRNACys (SepCysS-SepCysE-tRNACys), which is involved in the second reaction step of the indirect pathway, to 2.6 A resolution. Space group P6522, with unit-cell parameters a = b = 107.2, c = 551.1 A. Two heterodimers of a synthase SepCysS dimer, an enhancer SepCysE dimer and one tRNACys are observed in the asymmetric unit
crystal structure of the complex of the enzyme with translation factor SepCysE, 2.8 A resolution
structure of the SepCysE-SepCysS-tRNACys ternary complex, at a resolution of 2.6 A by molecular replacement. SepCysS recognizes the discriminator base U73 of tRNACys
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
C272A
loss of the ability to complement an Escherichia coli selA knockout strain, which cannot produce active formate dehydrogenase H due to the lack of selenocysteine incorporation
C64A
loss of the ability to complement an Escherichia coli selA knockout strain, which cannot produce active formate dehydrogenase H due to the lack of selenocysteine incorporation
C67A
loss of the ability to complement an Escherichia coli selA knockout strain, which cannot produce active formate dehydrogenase H due to the lack of selenocysteine incorporation
K234A
additional information
additional information
active-site cysteine residues Cys39, Cys42 and Cys247 are essential for enzymic activity
additional information
-
active-site cysteine residues Cys39, Cys42 and Cys247 are essential for enzymic activity
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
Q Sepharose FF column chromatography and FPLC Mono Q column chromatography
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
gene Mj1678 or pscS, functional complementation of a cysteinyl-tRNACys synthase mutant strain, phylogenetic analysis, expression in Escherichia coli
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REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Sauerwald, A.; Zhu, W.; Major, T.A.; Roy, H.; Palioura, S.; Jahn, D.; Whitman, W.B.; Yates, J.R.; Ibba, M.; Soell, D.
RNA-dependent cysteine biosynthesis in archea
Science
307
1969-1972
2005
Methanocaldococcus jannaschii, Methanococcus maripaludis (A4FWT8), Methanococcus maripaludis
Zhang, C.M.; Liu, C.; Slater, S.; Hou, Y.M.
Aminoacylation of tRNA with phosphoserine for synthesis of cysteinyl-tRNA(Cys)
Nat. Struct. Mol. Biol.
15
507-514
2008
Methanocaldococcus jannaschii, Methanocaldococcus jannaschii (Q59072)
Helgadottir, S.; Sinapah, S.; Soell, D.; Ling, J.
Mutational analysis of Sep-tRNA:Cys-tRNA synthase reveals critical residues for tRNA-dependent cysteine formation
FEBS Lett.
586
60-63
2012
Methanocaldococcus jannaschii (Q59072), Methanocaldococcus jannaschii
Liu, Y.; Dos Santos, P.C.; Zhu, X.; Orlando, R.; Dean, D.R.; Soell, D.; Yuan, J.
Catalytic mechanism of Sep-tRNA:Cys-tRNA synthase: sulfur transfer is mediated by disulfide and persulfide
J. Biol. Chem.
287
5426-5433
2012
Methanocaldococcus jannaschii (Q59072), Methanocaldococcus jannaschii, Methanocaldococcus jannaschii DSM 2661 (Q59072)
Liu, Y.; Nakamura, A.; Nakazawa, Y.; Asano, N.; Ford, K.A.; Hohn, M.J.; Tanaka, I.; Yao, M.; Sll, D.
Ancient translation factor is essential for tRNA-dependent cysteine biosynthesis in methanogenic archaea
Proc. Natl. Acad. Sci. USA
111
10520-10505
2014
Methanocaldococcus jannaschii (Q59072), Methanocaldococcus jannaschii DSM 2661 (Q59072)
Chen, M.; Nakazawa, Y.; Kubo, Y.; Asano, N.; Kato, K.; Tanaka, I.; Yao, M.
Crystallographic analysis of a subcomplex of the transsulfursome with tRNA for Cys-tRNACys synthesis
Acta Crystallogr. Sect. F
72
569-572
2016
Methanocaldococcus jannaschii (Q59072), Methanocaldococcus jannaschii DSM 2661 (Q59072)
Chen, M.; Kato, K.; Kubo, Y.; Tanaka, Y.; Liu, Y.; Long, F.; Whitman, W.B.; Lill, P.; Gatsogiannis, C.; Raunser, S.; Shimizu, N.; Shinoda, A.; Nakamura, A.; Tanaka, I.; Yao, M.
Structural basis for tRNA-dependent cysteine biosynthesis
Nat. Commun.
8
1521
2017
Methanocaldococcus jannaschii (Q59072), Methanocaldococcus jannaschii DSM 2661 (Q59072)
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