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Information on EC 3.6.5.5 - dynamin GTPase

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EC Tree
IUBMB Comments
An enzyme with a molecular mass of about 100 kDa that is involved in endocytosis and is instrumental in pinching off membrane vesicles.
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This record set is specific for:
UNIPROT: Q05193
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Word Map
The expected taxonomic range for this enzyme is: Eukaryota, Bacteria
Reaction Schemes
Synonyms
dynamin, dynamin-related protein 1, dynamin 2, d100, dynamin-2, dynamin 1, dynamin i, optic atrophy 1, dynamin-1, gtpase dynamin, more
SYNONYM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
dynamin 1
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dynamin I
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dynamin I GTPase
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dynI GTPase
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large GTPase
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multidomain GTPase
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B-dynamin
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-
-
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D100
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-
-
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Dynamin BREDNM19
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-
-
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Dynamin UDNM
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-
-
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Dynamin, brain
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-
-
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Dynamin, testicular
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-
-
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GTP phosphohydrolase
-
-
-
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GTPase
-
-
-
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guanine triphosphatase
-
-
-
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guanosine 5'-triphosphatase
-
-
-
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guanosine triphosphatase
-
-
-
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phosphatase, guanosine tri-
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-
-
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ribosomal GTPase
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-
-
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Shibire protein
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-
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T-dynamin
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-
-
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REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
hydrolysis of phosphoric ester
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-
-
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SYSTEMATIC NAME
IUBMB Comments
GTP phosphohydrolase (vesicle-releasing)
An enzyme with a molecular mass of about 100 kDa that is involved in endocytosis and is instrumental in pinching off membrane vesicles.
CAS REGISTRY NUMBER
COMMENTARY hide
9059-32-9
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SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
GTP + H2O
GDP + phosphate
show the reaction diagram
-
-
-
?
additional information
?
-
NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
GTP + H2O
GDP + phosphate
show the reaction diagram
-
-
-
?
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
(2-chloro-6-methylpyrimidin-4-yl)butylamine
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(2-chloro-6-methylpyrimidin-4-yl)cyclohexylamine
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(2-chloro-6-methylpyrimidin-4-yl)cyclopropylmethylpropylamine
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(2-chloro-6-methylpyrimidin-4-yl)decylamine
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(2-chloro-6-methylpyrimidin-4-yl)dimethylamine
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(2-chloro-6-methylpyrimidin-4-yl)ethylamine
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(2-chloro-6-methylpyrimidin-4-yl)hexylamine
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(2-chloro-6-methylpyrimidin-4-yl)octylamine
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(2-chloro-6-methylpyrimidin-4-yl)propylamine
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(2-chloro-6-methylpyrimidin-4-yl)tetradecylamine
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(4-chloro-6-methylpyrimidin-2-yl)(1-cyclopropylmethylpropyl)amine
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(4-chloro-6-methylpyrimidin-2-yl)-dimethylamine
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(4-chloro-6-methylpyrimidin-2-yl)butylamine
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(4-chloro-6-methylpyrimidin-2-yl)cyclohexylamine
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(4-chloro-6-methylpyrimidin-2-yl)decylamine
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(4-chloro-6-methylpyrimidin-2-yl)hexylamine
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(4-chloro-6-methylpyrimidin-2-yl)octylamine
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(4-chloro-6-methylpyrimidin-2-yl)propylamine
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(4-chloro-6-methylpyrimidin-2-yl)tetradecylamine
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2-(2-dimethylaminoethyl)-4-N-(didecylamino)-6-methylpyrimidine
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2-chloro-4-(2-dimethylaminopropylamine)-6-methylpyrimidine
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2-chloro-5-methyl-4-(4-methylpiperazin-1-yl)pyrimidine
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2-chloro-N-(4-methoxybenzyl)-6-methylpyrimidin-4-amine
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3-sulfo-N-(2-hydroxyethyl)-1,8-naphthalimide
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4-(2-dimethylaminoethyl)-2-N-(didecylamino)-6-methylpyrimidine
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4-amino-3-sulfo-N-(2-(dimethylamino)ethyl)-1,8-naphthalimide
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4-amino-3-sulfo-N-(2-(piperazin-1-yl)ethyl)-1,8-naphthalimide
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4-amino-3-sulfo-N-(2-aminobenzyl)-1,8-naphthalimide
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4-amino-3-sulfo-N-(2-aminoethyl)-1,8-naphthalimide
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4-amino-3-sulfo-N-(2-carboxyethyl)-1,8-naphthalimide
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4-amino-3-sulfo-N-(2-hydroxyethyl)-1,8-naphthalimide
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4-amino-3-sulfo-N-(2-mercaptoethyl)-1,8-naphthalimide
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4-amino-3-sulfo-N-(2-methoxyethyl)-1,8-naphthalimide
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4-amino-3-sulfo-N-(3-aminobenzyl)-1,8-naphthalimide
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4-amino-3-sulfo-N-(3-hydroxyphenyl)-1,8-naphthalimide
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4-amino-3-sulfo-N-(3-hydroxypropyl)-1,8-naphthalimide
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4-amino-3-sulfo-N-(4-aminobenzyl)-1,8-naphthalimide
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4-amino-3-sulfo-N-(4-carboxybenzyl)-1,8-naphthalimide
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4-amino-3-sulfo-N-(4-hydroxybenzyl)-1,8-naphthalimide
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4-amino-3-sulfo-N-(4-hydroxyphenyl)-1,8-naphthalimide
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4-amino-3-sulfo-N-(4-methoxyphenyl)-1,8-naphthalimide
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4-amino-3-sulfo-N-(5-hydroxyhexyl)-1,8-naphthalimide
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4-amino-3-sulfo-N-(5-hydroxypentyl)-1,8-naphthalimide
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4-amino-3-sulfo-N-(carboxymethyl)-1,8-naphthalimide
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4-amino-3-sulfo-N-(phenethyl)-1,8-naphthalimide
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4-amino-3-sulfo-N-benzyl-1,8-naphthalimide
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4-amino-3-sulfo-N-phenyl-1,8-naphthalimide
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4-chloro-6-methyl-2-(4-methylpiperazin-1-yl)pyrimidine
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4-chloro-N-(4-methoxybenzyl)-6-methylpyrimidin-2-amine
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4-sulfo-N-(2-hydroxyethyl)-1,8-naphthalimide
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N'-(2-chloro-6-methylpyrimidin-4-yl)ethane-1,2-diamine
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N'-(4-Chloro-6-methylpyrimidin-2-yl)-ethane-1,2-diamine
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N-(2-hydroxyethyl)-1,8-naphthalimide
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N-benzyl-2-chloro-6-methylpyrimidin-4-amine
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N-benzyl-4-chloro-6-methylpyrimidin-2-amine
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N-decyl-N'-(2-dimethylaminoethyl)-pyrimidine-4,6-diamine
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N-dodecyl-N'-(2-dimethylaminoethyl)pyrimidine-4,6-diamine
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N1-(4-chloro-6-methylpyrimidin-2-yl)-N3,N3-dimethylpropane-1,3-diamine
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N2-(2-dimethylaminoethyl)-6-methyl-N4-octadecylpyrimidine-2,4-diamine
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N2-(2-dimethylaminoethyl)-6-methyl-N4-propylpyrimidine-2,4-diamine
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N2-(2-dimethylaminoethyl)-6-methyl-N4-tetradecylpyrimidine-2,4-diamine
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N2-(2-dimethylaminoethyl)-N4-decyl-6-methylpyrimidine-2,4-diamine
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N2-(2-dimethylaminoethyl)-N4-hexyl-6-methylpyrimidine-2,4-diamine
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N2-(2-dimethylaminoethyl)-N4-octyl-6-methylpyrimidine-2,4-diamine
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N2-benzyl-N4-(2-dimethylaminoethyl)-6-methylpyrimidine-2,4-diamine
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N2-butyl-N4-(2-dimethylaminoethyl)-6-methylpyrimidine-2,4-diamine
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N2-cyclohexyl-N4-(2-dimethylaminoethyl)-6-methylpyrimidine-2,4-diamine
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N2-cyclopropylmethyl-N4-(2-dimethylamin-ethyl)-6-methyl-N2-propylpyrimidine-2,4-diamine
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N2-decyl-N4-(2-dimethylaminoethyl)pyrimidine-2,4-diamine
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N2-dodecyl-N4-(2-dimethylaminoethyl)-pyrimidine-2,4-diamine
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N2-sec-butyl-N4-(2-dimethylaminoethyl)-6-methylpyrimidine-2,4-diamine
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N4-(2-dimethylaminoethyl)-6-methyl-N2-octadecylpyrimidine-2,4-diamine
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N4-(2-dimethylaminoethyl)-6-methyl-N2-propylpyrimidine-2,4-diamine
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N4-(2-dimethylaminoethyl)-6-methyl-N2-tetradecylpyrimidine-2,4-diamine
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N4-(2-dimethylaminoethyl)-N2-decyl-6-methylpyrimidine-2,4-diamine
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N4-(2-dimethylaminoethyl)-N2-hexyl-6-methylpyrimidine-2,4-diamine
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N4-(2-dimethylaminoethyl)-N2-octyl-6-methylpyrimidine-2,4-diamine
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N4-Benzyl-N2-(2-dimethylaminoethyl)-6-methylpyrimidine-2,4-diamine
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N4-butyl-N2-(2-dimethylaminoethyl)-6-methylpyrimidine-2,4-diamine
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N4-cyclohexyl-N2-(2-dimethylaminoethyl)-6-methylpyrimidine-2,4-diamine
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N4-cyclopropylmethyl-N2-(2-dimethylamin-ethyl)-6-methyl-N2-propylpyrimidine-2,4-diamine
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N4-decyl-N2-(2-dimethylaminoethyl)pyrimidine-2,4-diamine
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N4-dodecyl-N2-(2-dimethylaminoethyl)pyrimidine-2,4-diamine
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N4-sec-butyl-N2-(2-dimethylaminoethyl)-6-methylpyrimidine-2,4-diamine
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sec-butyl-(2-chloro-6-methylpyrimidin-4-yl)amine
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sec-butyl-(4-chloro-6-methylpyrimidin-2-yl)amine
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[2-(2-chloro-6-methylpyrimidin-4-ylamino)ethyl]carbamic acid tert-butyl ester
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[2-(4-chloro-6-methylpyrimidin-2-ylamino)ethyl]carbamic acid tert-butyl ester
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additional information
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
liposome
liposome-stimulated GTPase activity of Dyn1
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IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.264
2-chloro-4-(2-dimethylaminopropylamine)-6-methylpyrimidine
Homo sapiens
pH and temperature not specified in the publication
0.3
3-sulfo-N-(2-hydroxyethyl)-1,8-naphthalimide
Homo sapiens
pH 7.4, 37°C
0.509
4-amino-3-sulfo-N-(2-(dimethylamino)ethyl)-1,8-naphthalimide
Homo sapiens
pH 7.4, 37°C
0.155
4-amino-3-sulfo-N-(2-aminobenzyl)-1,8-naphthalimide
Homo sapiens
pH 7.4, 37°C
0.3
4-amino-3-sulfo-N-(2-aminoethyl)-1,8-naphthalimide
Homo sapiens
pH 7.4, 37°C
0.094
4-amino-3-sulfo-N-(2-carboxyethyl)-1,8-naphthalimide
Homo sapiens
pH 7.4, 37°C
0.193
4-amino-3-sulfo-N-(2-hydroxyethyl)-1,8-naphthalimide
Homo sapiens
pH 7.4, 37°C
0.088
4-amino-3-sulfo-N-(3-aminobenzyl)-1,8-naphthalimide
Homo sapiens
pH 7.4, 37°C
0.159
4-amino-3-sulfo-N-(3-hydroxyphenyl)-1,8-naphthalimide
Homo sapiens
pH 7.4, 37°C
0.093
4-amino-3-sulfo-N-(3-hydroxypropyl)-1,8-naphthalimide
Homo sapiens
pH 7.4, 37°C
0.123
4-amino-3-sulfo-N-(4-aminobenzyl)-1,8-naphthalimide
Homo sapiens
pH 7.4, 37°C
0.0185
4-amino-3-sulfo-N-(4-carboxybenzyl)-1,8-naphthalimide
Homo sapiens
pH 7.4, 37°C
0.0448
4-amino-3-sulfo-N-(4-hydroxybenzyl)-1,8-naphthalimide
Homo sapiens
pH 7.4, 37°C
0.296
4-amino-3-sulfo-N-(4-hydroxyphenyl)-1,8-naphthalimide
Homo sapiens
pH 7.4, 37°C
0.113
4-amino-3-sulfo-N-(5-hydroxyhexyl)-1,8-naphthalimide
Homo sapiens
pH 7.4, 37°C
0.062
4-amino-3-sulfo-N-(5-hydroxypentyl)-1,8-naphthalimide
Homo sapiens
pH 7.4, 37°C
0.0191
4-amino-3-sulfo-N-(carboxymethyl)-1,8-naphthalimide
Homo sapiens
pH 7.4, 37°C
0.0703
4-amino-3-sulfo-N-benzyl-1,8-naphthalimide
Homo sapiens
pH 7.4, 37°C
0.3
4-amino-3-sulfo-N-phenyl-1,8-naphthalimide
Homo sapiens
pH 7.4, 37°C
0.3
4-sulfo-N-(2-hydroxyethyl)-1,8-naphthalimide
Homo sapiens
pH 7.4, 37°C
0.327
N1-(4-chloro-6-methylpyrimidin-2-yl)-N3,N3-dimethylpropane-1,3-diamine
Homo sapiens
pH and temperature not specified in the publication
additional information
additional information
Homo sapiens
IC50 values, overview
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pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
7.4
assay at
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
37
assay at
ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY hide
GeneOntology No.
LITERATURE
SOURCE
additional information
the enzyme domain PHD orientation serves as a conformation switch between cytosolic and membrane-bound states
-
Manually annotated by BRENDA team
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
evolution
dynamin is the prototype of a family of large multidomain GTPases. Dynamins and dynamin related proteins constitute a large family of atypical multidomain GTPases that share the common properties of low affinity for guanine nucleotides, high rate of GTP hydrolysis and the ability to oligomerize into helical structures
malfunction
the pleckstrin homology domain (PHD) conformational switch is impaired by a centronuclear myopathy-causing disease mutation, S619L, highlighting the physiological significance of its role in regulating dynamin function
physiological function
additional information
UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION?
DYN1_HUMAN
864
0
97408
Swiss-Prot
other Location (Reliability: 3)
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
additional information
CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
GTPase domain and the bundle signalling element of dynamin in the GDP-bound state, GG1, hanging drop vapour diffusion method, mixing of 0.0015 ml of 10 mg/ml GG1 protein solution containing 2 mM GDP and 2 mM MgCl2 with 0.0015 ml of reservoir solution containing 0.1 M Tris, pH 8.0, 26% PEG 3350, and 0.2 M NaSCN, and equilibration against 0.7 ml of reservoir solution, one week, 4°C, X-ray diffraction structure determination and analysis at 1.7-1.8 A resolution, molecular replacement using GG1GDP.AlFx (PDB ID 2X2E) as search model
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
K44A
dominant-negative dynamin mutant
S619L
site-directed mutagenesis, the pleckstrin homology domain (PHD) conformational switch is impaired by the centronuclear myopathy-causing disease mutation. The temperature-sensitive phenotype of the Dyn1S619L mutant reflects temperature-sensitive changes in the steady-state conformation(s) adopted by the PHD
Y354C
site-directed mutagenesis, interaction analysis with Dyn2L354C-IAEDANS mutant, membrane binding and consequent opening of PHD in mutants Dyn1Y354C-IAEDANS and Dyn2L354C-IAEDANS, overview
additional information
engineering of dynamin constructs locked in either the closed or open state by chemical cross-linking or deletion mutagenesis. Design of dynamin mutants to restrict the PHD in the closed (Dyn1Closed) or open (Dyn1DELTADELTA) state. The stimulation of GTPase activity of Dyn1DELTADELTA mutant by liposomes is reduced compared to the wild-type enzyme. Ability of wild-type Dyn1, and mutant Dyn1CC and Dyn1Closed to catalyze membrane fission and vesicle release from SUPER templates, overview
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
recombinant dynamin 1 GTPase domain GG1 from Escherichia coli strain BL21 (DE3) by glutathione affinity chromatography, tag cleavage by TEV protease, ultrafiltration, and gel filtration
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
expressed in a fibroblastoid cell line and in embryonic stem cells
gene DNM1, recombinant expression of the dynamin 1 GTPase domain GG1 from modified pGEX-4T1 vector containing a TEV protease site. The fragments are connected by a linker composed of eight amino acid residues (KHGTDSRV) in Escherichia coli strain BL21 (DE3)
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Liu, Y.W.; Surka, M.C.; Schroeter, T.; Lukiyanchuk, V.; Schmid, S.L.
Isoform and splice-variant specific functions of dynamin-2 revealed by analysis of conditional knock-out cells
Mol. Biol. Cell
19
5347-5359
2008
Rattus norvegicus (P21575), Rattus norvegicus (P39052), Rattus norvegicus (Q08877), Homo sapiens (Q05193)
Manually annotated by BRENDA team
Abdel-Hamid, M.K.; Macgregor, K.A.; Odell, L.R.; Chau, N.; Mariana, A.; Whiting, A.; Robinson, P.J.; McCluskey, A.
1,8-Naphthalimide derivatives: new leads against dynamin I GTPase activity
Org. Biomol. Chem.
13
8016-8028
2015
Homo sapiens (Q05193)
Manually annotated by BRENDA team
Anand, R.; Eschenburg, S.; Reubold, T.F.
Crystal structure of the GTPase domain and the bundle signalling element of dynamin in the GDP state
Biochem. Biophys. Res. Commun.
469
76-80
2016
Homo sapiens (Q05193)
Manually annotated by BRENDA team
Srinivasan, S.; Dharmarajan, V.; Reed, D.K.; Griffin, P.R.; Schmid, S.L.
Identification and function of conformational dynamics in the multidomain GTPase dynamin
EMBO J.
35
443-457
2016
Homo sapiens (Q05193)
Manually annotated by BRENDA team
Odell, L.R.; Abdel-Hamid, M.K.; Hill, T.A.; Chau, N.; Young, K.A.; Deane, F.M.; Sakoff, J.A.; Andersson, S.; Daniel, J.A.; Robinson, P.J.; McCluskey, A.
Pyrimidine-based inhibitors of dynamin I GTPase activity competitive inhibition at the pleckstrin homology domain
J. Med. Chem.
60
349-361
2017
Homo sapiens (Q05193)
Manually annotated by BRENDA team