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Information on EC 5.6.1.3 - plus-end-directed kinesin ATPase

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EC Tree
IUBMB Comments
Kinesins are a family of motor proteins that move unidirectionally along microtubules as they hydrolyse ATP. The enzymes described here move towards the plus end of the microtubule, in contrast to EC 5.6.1.2, dynein ATPase and EC 5.6.1.4, minus-end-directed kinesin ATPase. They are involved in organelle movement in mitosis and meiosis, and also power vesicular trafficking toward the synapse in neurons. The motor domain, which contains the ATP- and microtubule-binding activities, is located at the N-terminus while the C-terminus links to the cargo being transported.
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UNIPROT: P33174
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Word Map
The enzyme appears in viruses and cellular organisms
Synonyms
kinesin, kinesin-1, kif3a, kinesin-5, kif1a, kif11, kif4a, kifc1, kinesin-2, kif5b, more
SYNONYM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
KIF4 ATPase
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kinesin
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REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
hydrolysis of phosphoric ester
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SYSTEMATIC NAME
IUBMB Comments
kinesin ATP phosphohydrolase (plus-end-directed)
Kinesins are a family of motor proteins that move unidirectionally along microtubules as they hydrolyse ATP. The enzymes described here move towards the plus end of the microtubule, in contrast to EC 5.6.1.2, dynein ATPase and EC 5.6.1.4, minus-end-directed kinesin ATPase. They are involved in organelle movement in mitosis and meiosis, and also power vesicular trafficking toward the synapse in neurons. The motor domain, which contains the ATP- and microtubule-binding activities, is located at the N-terminus while the C-terminus links to the cargo being transported.
CAS REGISTRY NUMBER
COMMENTARY hide
9000-83-3
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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
ATP + H2O + a kinesin associated with a microtubule at position n
ADP + phosphate + a kinesin associated with a microtubule at position n+1 (toward the plus end)
show the reaction diagram
additional information
?
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KIF4 specifically binds to the microtubule, enzyme interaction with tubulin, the KIF4-specific Q248 and K249 form possible hydrogen bonds with Y108 of helix H3' of alpha-tubulin. Microtubule filament binding by enzyme KIF4, around the center line of the microtubule protofilament, the helix-alpha4-mediated microtubule-binding site is located and fitted into the intra-tubulin dimer groove
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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
ATP + H2O + a kinesin associated with a microtubule at position n
ADP + phosphate + a kinesin associated with a microtubule at position n+1 (toward the plus end)
show the reaction diagram
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-
-
?
additional information
?
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KIF4 specifically binds to the microtubule, enzyme interaction with tubulin, the KIF4-specific Q248 and K249 form possible hydrogen bonds with Y108 of helix H3' of alpha-tubulin. Microtubule filament binding by enzyme KIF4, around the center line of the microtubule protofilament, the helix-alpha4-mediated microtubule-binding site is located and fitted into the intra-tubulin dimer groove
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?
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
Mg2+
required
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
additional information
microtubule-stimulated ATPase activity of wild-type monomeric KIF4
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KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.00634
ATP
wild-type KIF4 enzyme, pH and temperature not specified in the publication
additional information
additional information
Michaelis-Menten kinetics, and steady-state ATPase activities of three types of chimeric construct, overview
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TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
42.1
ATP
wild-type KIF4 enzyme, pH and temperature not specified in the publication
ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
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SwissProt
Manually annotated by BRENDA team
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
evolution
the enzyme KIF4 belongs to the kinesin superfamily
physiological function
kinesin superfamily proteins are microtubule-based molecular motors driven by the energy derived from the hydrolysis of ATP. The ATP binding step is crucial both for the power stroke to produce motility and for the inter-domain regulation of ATPase activity to guarantee the processive movement of dimeric kinesin superfamily proteins. The binding of KIF4 to the microtubule may affect the interaction within the tubulin dimer by increasing or decreasing the curvature of the intra-tubulin dimer interface with some twist, molecular mechanism by which KIF4 inhibits microtubule dynamics
additional information
tubulin and ATP binding structure analysis, sequential docking of the neck linker induced by ATP binding (isomerization), modeling. Backdoor formation stabilizes the two switch regions and induces full docking of the neck linker through a conformational change to switch II, affecting the conformation of loops L11-alpha4-L12-alpha5-L13 in switch II. Overall architecture of the KIF4 motor domain and structure-function relationship, overview
UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION?
KIF4_MOUSE
1231
0
139519
Swiss-Prot
other Location (Reliability: 2)
CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
His7-tagged KIF4 motor domain construct KIF4-344 in complex with AMPPNP, sitting drop vapour diffusion method, mixing of 15 mg/ml protein in 10 mM Tris–HCl, pH 8.0, 100 mM NaCl, and 1 mM DTT with a reservoir solution containing 28% w/v PEG 4000, 100 mM Tris-HCl, pH 8.5, and 200 mM sodium acetate, in the presence of 5 mM AMPPNP, X-ray diffraction strcuture determination and analysis at 1.71 A resolution, molecular replacement and modeling
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
recombinant His7-tagged KIF4 motor domain construct KIF4-344 from Escherichia coli strain BL21(DE3) by nickel affinity and cation exchange chromatography, followed gel filtration and dialysis
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
recombinant expression of a KIF4 motor domain construct, KIF4-344 comprising residues 1-344 of KIF4 followed by a His7-tag in Escherichia coli strain BL21(DE3)
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Chang, Q.; Nitta, R.; Inoue, S.; Hirokawa, N.
Structural basis for the ATP-induced isomerization of kinesin
J. Mol. Biol.
425
1869-1880
2013
Mus musculus (P33174)
Manually annotated by BRENDA team