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Information on EC 2.7.13.3 - histidine kinase and Organism(s) Thermotoga maritima and UniProt Accession Q56310
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2.7.13.3 histidine kinaseIUBMB Comments
This entry has been included to accommodate those protein-histidine kinases for which the phosphorylation site has not been established (i.e. either the pros- or tele-nitrogen of histidine). A number of histones can act as acceptor.
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Word Map
- 2.7.13.3
- autophosphorylation
- photoreceptors
-
far-red
- seedling
-
phosphorelay
- chromophore
-
perception
-
regulons
- hypocotyls
-
quorum
-
perceived
- pfr
-
chemoreceptor
-
senses
-
light-induced
- chey
-
flagellar
- synechocystis
-
etiolated
- caulobacter
-
photomorphogenesis
-
transmitter
-
quorum-sensing
-
fluence
- biliverdin
-
cryptochrome
- crescentus
-
methyl-accepting
-
dark-grown
- radiodurans
-
transphosphorylation
-
autoinducer
-
histidine-containing
-
chemosensory
-
photomorphogenic
-
extracytoplasmic
- arca
- deinococcus
- phototropins
- tetrapyrrole
- ompc
- c-di-gmp
-
diguanylate
- spo0a
-
four-helix
-
gravitropism
-
photoresponses
-
non-cognate
- xanthus
-
photoisomerization
- synthesis
- medicine
The taxonomic range for the selected organisms is: Thermotoga maritima
The enzyme appears in selected viruses and cellular organisms
The enzyme appears in selected viruses and cellular organisms
Synonyms
histidine kinase, sensor kinase, sensor protein, phytochrome a, ethylene receptor, sensor histidine kinase, bacteriophytochrome, ornithine decarboxylase antizyme, chemotaxis protein, hybrid histidine kinase, 
more
topSYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
phospho group transfer
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-
-
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SYSTEMATIC NAME
IUBMB Comments
ATP:protein-L-histidine N-phosphotransferase
This entry has been included to accommodate those protein-histidine kinases for which the phosphorylation site has not been established (i.e. either the pros- or tele-nitrogen of histidine). A number of histones can act as acceptor.
CAS REGISTRY NUMBER
COMMENTARY
99283-67-7
protein-histidine kinases, EC 2.7.13.1, EC 2.7.13.2, and EC 2.7.13.3 are not distinguished in Chemical Abstracts
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
ATP + protein L-histidine
ADP + protein N-phospho-L-histidine
the two active sites of CheA homodimers exhibit large differences in their interactions with ATP
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-
?
additional information
?
-
-
histidine kinase performs autophosphorylation. The His-containing substrate domain (P1) is sequestered by interactions that depend upon P1 of the adjacent subunit. Non-hydrolyzable ATP analogues (but not ATP or ADP) release P1 from the protein core (domains P3P4P5) and increase its mobility. Autophosphorylation is possible only when the subunit with a functional P4 domain trans phosphorylates a functional P1 domain of the opposing subunit
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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
COFACTOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
ATP
-
residue Ser492 resides on the ATP lid, near to the Mg2+ ion that coordinates the gamma-phosphate of ATP in the P4 active site
additional information
-
non-hydrolyzable ATP analogues (but not ATP or ADP) release P1 from the protein core (domains P3P4P5) and increase its mobility
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METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
3,6-diamino-5-cyano-4-phenyl-thieno[2,3-b]pyridine-2-carboxylic acid (4-bromo-phenyl)amide
-
competitive inhibitor of the coupled reaction of histidine kinase HpkA HK and the cognate response regulator DrrA RR
6-(2,6-dimethylmorpholin-4-yl)-9H-purine
lead compound for inhibitor development
7-(4-fluorophenyl)-6-(pyridin-4-yl)-5H-pyrrolo[2,3-b]pyrazine
compound is able to displace ADP-BODIPY from the HK853 ATP-binding domain and inhibits HK853 and Streptococcus pneumoniaeVicK activity at non-aggregating concentrations. Compound may only poorly penetrate the bacterial envelope or lacks sufficient potency to yield measurable effects
N,N-dipropyl-9H-purin-6-amine
lead compound for inhibitor development
N-(2-phenylethyl)-9H-purin-6-amine
lead compound for inhibitor development
N-(3,3,5-trimethylcyclohexyl)-9H-purin-6-amine
lead compound for inhibitor development
N-phenyl-9H-purin-6-amine
does not aggregate HK853 even at above 1.25 mM
additional information
not inhibitory at 1.25 mM: idelalisib, ibrutinib
-
additional information
structure-activity relationship assessment of adenine-based inhibitors using biochemical and docking methods. Interaction of an inhibitor's amine group with the conserved active-site Asp is essential for activity and likely dictates its orientation in the binding pocket. A N-NH-N triad in the inhibitor scaffold is highly preferred for binding to conserved Gly:Asp:Asn residues. Hydrophobic electron-withdrawing groups at several positions in the adenine core enhance potency. Groups that target the ATP-lid portion of the catalytic domain, such as a six-membered ring, confer selectivity for histidine kinases
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Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.00062
3,6-diamino-5-cyano-4-phenyl-thieno[2,3-b]pyridine-2-carboxylic acid (4-bromo-phenyl)amide
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-
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.126
2-chloro-9-D-ribofuranosyl-9H-purin-6-amine
Thermotoga maritima
23°C, pH not specified in the publication
0.095
2-chloro-9-methyl-9H-purin-6-amine
Thermotoga maritima
23°C, pH not specified in the publication
0.156
2-chloro-9H-purin-6-amine
Thermotoga maritima
23°C, pH not specified in the publication
0.0953
6-(2,6-dimethylmorpholin-4-yl)-9H-purine
Thermotoga maritima
23°C, pH not specified in the publication
0.118
6-chloro-9-D-ribofuranosyl-9H-purin-2-amine
Thermotoga maritima
23°C, pH not specified in the publication
0.0237
7-(4-fluorophenyl)-6-(pyridin-4-yl)-5H-pyrrolo[2,3-b]pyrazine
Thermotoga maritima
pH not specified in the publication, temperature not specified in the publication
0.0496
N,N-dipropyl-9H-purin-6-amine
Thermotoga maritima
23°C, pH not specified in the publication
0.145
N-(2-phenylethyl)-9H-purin-6-amine
Thermotoga maritima
23°C, pH not specified in the publication
0.131
N-(3,3,5-trimethylcyclohexyl)-9H-purin-6-amine
Thermotoga maritima
23°C, pH not specified in the publication
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
physiological function
CheA is a central component of the chemotaxis signal transduction pathway that allows prokaryotic cells to control their movements in response to environmental cues
evolution
-
CheA differs from sensor histidine kinases in several ways: CheA does not contain a transmembrane domain, relying instead on P5 and CheW for interaction with transmembrane components. It has the phosphorylatable His residue on a separate domain (P1) instead of the dimerization domain (P3), and it utilizes a separate docking domain (P2) for CheY. P2 is not necessary for phosphotransfer to the response regulator CheY per se but variants lacking the P2 domain (DELTAP2) exhibit a reduced phosphotransfer rate relative to full-length CheA (CheAFL) and support a lower extent of chemotaxis. The linkers between the CheA domains play important roles in CheA activity
physiological function
-
CheA differs from sensor histidine kinases in several ways: CheA does not contain a transmembrane domain, relying instead on P5 and CheW for interaction with transmembrane components. It has the phosphorylatable His residue on a separate domain (P1) instead of the dimerization domain (P3), and it utilizes a separate docking domain (P2) for CheY. P2 is not necessary for phosphotransfer to the response regulator CheY per se but variants lacking the P2 domain (DELTAP2) exhibit a reduced phosphotransfer rate relative to full-length CheA (CheAFL) and support a lower extent of chemotaxis. The linkers between the CheA domains play important roles in CheA activity
PDB
SCOP
CATH
UNIPROT
ORGANISM
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
P3P4 domain structure of Thermotoga maritima CheA, vapor diffusion method, mixing of 0.001 ml of 0.7 mM protein in 50 mM HEPES, pH 7.5, 150 mM NaCl, and 2 mM DTT, with 0.001 ml of reservoir solution containing 0.5 M ammonium sulfate, 0.1 M sodium citrate tribasic dihydrate, pH 5.6, and 1.0 M lithium sulfate monohydrate, 4°C, X-ray small angle diffraction structure determination and analysis at 3.0 A resolution, molecular replacement and modelling
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ThkA complexed with the response regulator TrrA, by the batch method, X-ray crystallography at a resolution of 4.2 A, 2fold symmetry, two monomeric TrrAs bind to the ThkA dimer
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
D449A
-
site-directed mutagenesis, the mutation in the ATP-binding pocket prevents nucleotide binding
H405Y
-
site-directed mutagenesis, the mutation abrogates the kinase activity
H45K
-
site-directed mutagenesis, a CheAFL variant that lacks the substrate His
H45K/H405Y
-
site-directed mutagenesis, the mutant shows reduced kinase activity compared to the wild-type
additional information
additional information
delta408ThkA, includes the PAS-sensor, the DHp and CA domains, and delta 517ThkA without the PAS-sensor domain, both are fully active in the autophosphorylation reaction
additional information
-
delta408ThkA, includes the PAS-sensor, the DHp and CA domains, and delta 517ThkA without the PAS-sensor domain, both are fully active in the autophosphorylation reaction
additional information
-
disulfide cross-linking of mutant enzymes, overview
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
additional information
responsible role of the response regulator TrrA for the feedback regulation of sensing and/or kinase activities of ThkA
additional information
-
responsible role of the response regulator TrrA for the feedback regulation of sensing and/or kinase activities of ThkA
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Bilwes, A.M.; Alex, L.A.; Crane, B.R.; Simon, M.I.
Structure of CheA, a signal-transducing histidine kinase
Cell
96
131-141
1999
Thermotoga maritima (Q56310), Thermotoga maritima
Nelson, K.E.; Clayton, R.A.; Gill, S.R.; Gwinn, M.L.; et al.
Evidence for lateral gene transfer between Archaea and bacteria from genome sequence of Thermotoga maritima
Nature
399
323-329
1999
Thermotoga maritima (Q56310)
Swanson, R.V.; Sanna, M.G.; Simon, M.I.
Thermostable chemotaxis proteins from the hyperthermophilic bacterium Thermotoga maritima
J. Bacteriol.
178
484-489
1996
Thermotoga maritima (Q56310)
Gilmour, R.; Foster, J.E.; Sheng, Q.; McClain, J.R.; Riley, A.; Sun, P.M.; Ng, W.L.; Yan, D.; Nicas, T.I.; Henry, K.; Winkler, M.E.
New class of competitive inhibitor of bacterial histidine kinases
J. Bacteriol.
187
8196-8200
2005
Thermotoga maritima
Yamada, S.; Akiyama, S.; Sugimoto, H.; Kumita, H.; Ito, K.; Fujisawa, T.; Nakamura, H.; Shiro, Y.
The signaling pathway in histidine kinase and the response regulator complex revealed by X-ray crystallography and solution scattering
J. Mol. Biol.
362
123-139
2006
Thermotoga maritima (Q9X180), Thermotoga maritima
Greenswag, A.R.; Muok, A.; Li, X.; Crane, B.R.
Conformational transitions that enable histidine kinase autophosphorylation and receptor array integration
J. Mol. Biol.
427
3890-3907
2015
Thermotoga maritima
Eaton, A.; Stewart, R.
The two active sites of thermotoga maritima CheA dimers bind ATP with dramatically different affinities
Biochemistry
48
6412-6422
2009
Thermotoga maritima (Q56310)
Wilke, K.; Fihn, C.; Carlson, E.
Screening serine/threonine and tyrosine kinase inhibitors for histidine kinase inhibition
Bioorg. Med. Chem.
26
5322-5326
2018
Thermotoga maritima (Q9WZV7), Thermotoga maritima DSM 3109 (Q9WZV7)
EXTERNAL LINKS (specific for EC-Number 2.7.13.3)
Transporter Classification Database (TCDB): 9.B.33.1.1, 9.B.238.3.5, 9.B.33.1.2, 2.A.21.9.1, 2.A.21.9.2, 2.A.123.2.13
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