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Information on EC 2.1.1.2 - guanidinoacetate N-methyltransferase and Organism(s) Rattus norvegicus and UniProt Accession P10868
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2.1.1.2 guanidinoacetate N-methyltransferaseSpecify your search results
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The taxonomic range for the selected organisms is: Rattus norvegicus
The expected taxonomic range for this enzyme is: Eukaryota, Bacteria
The expected taxonomic range for this enzyme is: Eukaryota, Bacteria
Reaction Schemes
Synonyms
guanidinoacetate methyltransferase, guanidinoacetate n-methyltransferase, guanidoacetate methyltransferase, n-guanidinoacetate methyltransferase, s-adenosyl-l-methionine:n-guanidinoacetate methyltransferase, 
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topSYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
GA methylpherase
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guanidinoacetate methyltransferase
guanidinoacetate transmethylase
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guanidoacetate methyltransferase
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methionine-guanidinoacetic transmethylase
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guanidinoacetate methyltransferase
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REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
S-adenosyl-L-methionine + guanidinoacetate = S-adenosyl-L-homocysteine + creatine
mechanism
S-adenosyl-L-methionine + guanidinoacetate = S-adenosyl-L-homocysteine + creatine
computer model of the reaction mechanism: by self-consistent-charge density functional tight binding/molecular mechanics, the bond lengths in the concerted mechanisms transition state is 1.26 A for both the OD1 (Asp-134)-HE (guanidinoacetate) and HE (guanidinoacetate)-NE (guanidinoacetate) bonds, and 2.47 and 2.03 A for the S8 (S-adenosyl-L-methionine)-C9 (S-adenosyl-L-methionine) and C9 (S-adenosyl-L-methionine)-NE (guanidinoacetate) bonds, respectively. The potential-energy barrier (delta E++) determined by single-point B3LYP/6-31+G*//MM is 18.9 kcal/mol. The contributions of the entropy (-TdeltaS++) and zero-point energy corrections delta(ZPE)++ by normal mode analysis are 2.3 kcal/mol and -1.7 kcal/mol, respectively. The activation enthalpy of this concerted mechanism is deltaH++ = 17.2 kcal/mol. The calculated free-energy barrier for the concerted mechanism is deltaG++ = 19.5 kcal/mol.
S-adenosyl-L-methionine + guanidinoacetate = S-adenosyl-L-homocysteine + creatine
the hybrid density functional theory (DFT) method B3LYP is used to examine the reaction mechanism: The methyl group transfer from S-adenosylmethionine to NE of guanidinoacetate occurs concertedly with a proton transfer from NE to the neighboring OD1 of Asp134.
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
methyl group transfer
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PATHWAY SOURCE
PATHWAYS
BRENDA
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SYSTEMATIC NAME
IUBMB Comments
S-adenosyl-L-methionine:N-guanidinoacetate methyltransferase
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CAS REGISTRY NUMBER
COMMENTARY
9029-75-8
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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
S-adenosyl-L-methionine + guanidinoacetate
S-adenosyl-L-homocysteine + creatine
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-
?
S-adenosyl-L-methionine + guanidinoacetate
S-adenosyl-L-homocysteine + creatine
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-
?
S-adenosyl-L-methionine + guanidinoacetate
S-adenosyl-L-homocysteine + creatine
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-
-
?
S-adenosyl-L-methionine + guanidinoacetate
S-adenosyl-L-homocysteine + creatine
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-
-
?
S-adenosyl-L-methionine + guanidinoacetate
S-adenosyl-L-homocysteine + creatine
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-
-
?
S-adenosyl-L-methionine + guanidinoacetate
S-adenosyl-L-homocysteine + creatine
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-
-
?
S-adenosyl-L-methionine + guanidinoacetate
S-adenosyl-L-homocysteine + creatine
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-
-
?
S-adenosyl-L-methionine + guanidinoacetate
S-adenosyl-L-homocysteine + creatine
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-
-
?
S-adenosyl-L-methionine + guanidinoacetate
S-adenosyl-L-homocysteine + creatine
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-
-
?
S-adenosyl-L-methionine + guanidinoacetate
S-adenosyl-L-homocysteine + creatine
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-
-
?
S-adenosyl-L-methionine + guanidinoacetate
S-adenosyl-L-homocysteine + creatine
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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
S-adenosyl-L-methionine + guanidinoacetate
S-adenosyl-L-homocysteine + creatine
-
-
?
S-adenosyl-L-methionine + guanidinoacetate
S-adenosyl-L-homocysteine + creatine
-
-
?
S-adenosyl-L-methionine + guanidinoacetate
S-adenosyl-L-homocysteine + creatine
-
-
-
?
S-adenosyl-L-methionine + guanidinoacetate
S-adenosyl-L-homocysteine + creatine
-
-
-
?
S-adenosyl-L-methionine + guanidinoacetate
S-adenosyl-L-homocysteine + creatine
-
-
-
?
S-adenosyl-L-methionine + guanidinoacetate
S-adenosyl-L-homocysteine + creatine
-
-
-
?
S-adenosyl-L-methionine + guanidinoacetate
S-adenosyl-L-homocysteine + creatine
-
-
-
?
S-adenosyl-L-methionine + guanidinoacetate
S-adenosyl-L-homocysteine + creatine
-
-
-
?
S-adenosyl-L-methionine + guanidinoacetate
S-adenosyl-L-homocysteine + creatine
-
-
-
?
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
additional information
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complete and irreversible inactivation by ultraviolet irradiation
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glutathione
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oxidized form, S-adenosylmethionine protects against inactivation
glutathione
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readily reactivated by reduced glutathione, substrates do not protect against inactivation, guanidinoacetate together with sinefungin protects against inactivation, can be reactivated with thiol compounds
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
glutathione
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required for maximum activity, can be replaced by other reducing agents
additional information
-
hepatic GAMT activity does not differ between rats fed creatine-free or creatine-supplemented diets
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KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
additional information
additional information
all mutant enzymes listed with Km
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additional information
additional information
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all mutant enzymes listed with Km
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TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
additional information
additional information
all mutant enzymes listed with turnover
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additional information
additional information
-
all mutant enzymes listed with turnover
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Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
in embryos at 12.5 days of gestation guanidinoacetate N-methyltransferase is detectable in the hepatic primordium only, with all other tissues being negative. Non-radioactive in situ hybridization (58°C for 40 h in 5 x SSC, 50% formamide and 40 microg/ml salmon sperm DNA) with digoxigenin-labeled antisense and sense riboprobes (400 ng/ml) for rat guanidinoacetate N-methyltransferase. guanidinoacetate N-methyltransferase proteins are detected with rabbit polyclonal antibodies
in embryos at 18.5 days of gestation guanidinoacetate N-methyltransferase is detectable. Non-radioactive in situ hybridization (58°C for 40 h in 5 x SSC, 50% formamide and 40 microg/ml salmon sperm DNA) with digoxigenin-labeled antisense and sense riboprobes (400 ng/ml) for rat guanidinoacetate N-methyltransferase. guanidinoacetate N-methyltransferase proteins are detected with rabbit polyclonal antibodies
in embryos at 15.5 and 18.5 days of gestation guanidinoacetate N-methyltransferase is detectable in pancreas. Non-radioactive in situ hybridization (58°C for 40 h in 5 x SSC, 50% formamide and 40 microg/ml salmon sperm DNA) with digoxigenin-labeled antisense and sense riboprobes (400 ng/ml) for rat guanidinoacetate N-methyltransferase. guanidinoacetate N-methyltransferase proteins are detected with rabbit polyclonal antibodies
in embryos at 18.5 days of gestation guanidinoacetate N-methyltransferase is detectable. Non-radioactive in situ hybridization (58°C for 40 h in 5 x SSC, 50% formamide and 40 microg/ml salmon sperm DNA) with digoxigenin-labeled antisense and sense riboprobes (400 ng/ml) for rat guanidinoacetate N-methyltransferase. guanidinoacetate N-methyltransferase proteins are detected with rabbit polyclonal antibodies
additional information
guanidinoacetate N-methyltransferase can not be detected in kidney of embryos of 12.5, 15.5 and 18.5 days of gestation. Non-radioactive in situ hybridization (58°C for 40 h in 5 x SSC, 50% formamide and 40 microg/ml salmon sperm DNA) with digoxigenin-labeled antisense and sense riboprobes (400 ng/ml) for rat guanidinoacetate N-methyltransferase. guanidinoacetate N-methyltransferase proteins are detected with rabbit polyclonal antibodies
all parts of brain, neurons and glia, very low levels in astrocytes
in embryos at 15.5 days of gestation guanidinoacetate N-methyltransferase is detectable in pons and striatum. In embryos at 18.5 days of gestation guanidinoacetate N-methyltransferase is detectable in neocortex, hippocampus, striatum, pallidum and spinal cord. Non-radioactive in situ hybridization (58°C for 40 h in 5 x SSC, 50% formamide and 40 microg/ml salmon sperm DNA) with digoxigenin-labeled antisense and sense riboprobes (400 ng/ml) for rat guanidinoacetate N-methyltransferase. guanidinoacetate N-methyltransferase proteins are detected with rabbit polyclonal antibodies
in embryos at 15.5 and 18.5 days of gestation guanidinoacetate N-methyltransferase is detectable in liver. Non-radioactive in situ hybridization (58°C for 40 h in 5 x SSC, 50% formamide and 40 microg/ml salmon sperm DNA) with digoxigenin-labeled antisense and sense riboprobes (400 ng/ml) for rat guanidinoacetate N-methyltransferase. guanidinoacetate N-methyltransferase proteins are detected with rabbit polyclonal antibodies
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
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). GAMT_RAT
236
0
26407
Swiss-Prot
other Location (Reliability: 2)
PDB
SCOP
CATH
UNIPROT
ORGANISM
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
26000
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
in complex with S-adenosylhomocysteine and guanidinoacetate, and in complex with S-adenosyl-homocysteine and guanidine
in complex with S-adenosyl-L-methionine in monoclinic and tetragonal modification
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PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
E45D
decrease in kcat-value, increase in Km-value of S-adenosyl-L-methionine
E45Q
decrease in kcat-value, increase in Km-value of S-adenosyl-L-methionine
Y136F
Y136V
Y136F
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retains considerable activity, structural changes compared to wild-type
TEMPERATURE STABILITY
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
GENERAL STABILITY
ORGANISM
UNIPROT
LITERATURE
inactivated during purification, can be reactivated by addition of a thiol
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STORAGE STABILITY
ORGANISM
UNIPROT
LITERATURE
-20°C, 10 mM phosphate buffer, pH 7.2, 1 mM EDTA, 0.1 M NaCl, concentrated by ultrafiltration
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PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
inactivated during purification, can be reactivated by addition of a thiol
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CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Ogawa, H.; Ishiguro, Y.; Fujioka, M.
Guanidoacetate methyltransferase from rat liver: purification, properties, and evidence for the involvement of sulfhydryl groups for activity
Arch. Biochem. Biophys.
226
265-275
1983
Rattus norvegicus
Ogawa, H.; Date, T.; Gomi, T.; Konishi, K.; Pitot, H.C.; Cantoni, G.L.; Fujioka, M.
Molecular cloning, sequence analysis, and expression in Escherichia coli of the cDNA for guanidinoacetate methyltransferase from rat liver
Proc. Natl. Acad. Sci. USA
85
694-698
1988
Rattus norvegicus
Fujioka, M.; Konishi, K.; Takata, Y.
Recombinant rat liver guanidinoacetate methyltransferase: reactivity and function of sulfhydryl groups
Biochemistry
27
7658-7664
1988
Rattus norvegicus
Konishi, K.; Fujioka, M.
Reversible inactivation of recombinant rat liver guanidinoacetate methyltransferase by glutathione disulfide
Arch. Biochem. Biophys.
289
90-96
1991
Rattus norvegicus
Takata, Y.; Fujioka, M.
Identification of a tyrosine residue in rat guanidinoacetate methyltransferase that is photolabeled with S-adenosyl-L-methionine
Biochemistry
31
4369-4374
1992
Rattus norvegicus
Takata, Y.; Konishi, K.; Gomi, T.; Fujioka, M.
Rat guanidinoacetate methyltransferase. Effect of site-directed alteration of an aspartic acid residue that is conserved across most mammalian S-adenosylmethionine-dependent methyltransferases
J. Biol. Chem.
269
5537-5542
1994
Rattus norvegicus (P10868)
Hamahata, A.; Takata, Y.; Gomi, T.; Fujioka, M.
Probing the S-adenosylmethionine-binding site of rat guanidinoacetate methyltransferase: effect of site-directed mutagenesis of residues that are conserved across mammalian non-nucleic acid methyltransferases
Biochem. J.
317
141-145
1996
Rattus norvegicus
-
Braissant, O.; Henry, H.; Loup, M.; Eilers, B.; Bachmann, C.
Endogenous synthesis and transport of creatine in the rat brain: an in situ hybridization study
Mol. Brain Res.
86
193-201
2001
Rattus norvegicus (P10868)
Komoto, J.; Huang, Y.; Takata, Y.; Yamada, T.; Konishi, K.; Ogawa, H.; Gomi, T.; Fujioka, M.; Takusagawa, F.
Crystal structure of guanidinoacetate methyltransferase from rat liver: A model structure of protein arginine methyltransferase
J. Mol. Biol.
320
223-235
2002
Rattus norvegicus
Komoto, J.; Takata, Y.; Yamada, T.; Konishi, K.; Ogawa, H.; Gomi, T.; Fujioka, M.; Takusagawa, F.
Monoclinic guanidinoacetate methyltransferase and gadolinium ion-binding characteristics
Acta Crystallogr. Sect. D
59
1589-1596
2003
Rattus norvegicus
Komoto, J.; Yamada, T.; Takata, Y.; Konishi, K.; Ogawa, H.; Gomi, T.; Fujioka, M.; Takusagawa, F.
Catalytic mechanism of guanidinoacetate methyltransferase: crystal structures of guanidinoacetate methyltransferase ternary complexes
Biochemistry
43
14385-14394
2004
Rattus norvegicus (P10868)
Braissant, O.; Henry, H.; Villard, A.; Speer, O.; Wallimann, T.; Bachmann, C.
Creatine synthesis and transport during rat embryogenesis: Spatiotemporal expression of AGAT, GAMT and CT1
BMC Dev. Biol.
5
9
2005
Rattus norvegicus (P10868)
Velichkova, P.; Himo, F.
Theoretical study of the methyl transfer in guanidinoacetate methyltransferase
J. Phys. Chem. B
110
16-19
2006
Rattus norvegicus (P10868)
Zhang, X.; Bruice, T.C.
Reaction mechanism of guanidinoacetate methyltransferase, concerted or step-wise
Proc. Natl. Acad. Sci. USA
103
16141-16146
2006
Rattus norvegicus (P10868)
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