Activating Compound | Comment | Organism | Structure |
---|---|---|---|
additional information | a sequential kinase activation model may involve helical bending of the DHp domain and repositioning of the CA domains. Model of VicK autokinase activation, overview | Streptococcus mutans |
Crystallization (Comment) | Organism |
---|---|
complete cytoplasmic region of enzyme VicK, X-ray diffraction structure determination and analysis | Streptococcus mutans |
purified full-length enzyme, X-ray diffraction structure determination and analysis at 3 A resolution, modeling | Streptococcus mutans serotype c |
Protein Variants | Comment | Organism |
---|---|---|
D326A/N337A | site-directed mutagenesis, the mutant is inactive in autophosphorylation | Streptococcus mutans |
D326A/N337A | site-directed mutagenesis, the mutation abolishes VicK autokinase activity | Streptococcus mutans serotype c |
D326A/Q330A | site-directed mutagenesis, the mutant shows highly reduced autophosphorylation activity compared to the wild-type enzyme | Streptococcus mutans |
D326A/Q330A | site-directed mutagenesis, the mutation highly suppresses VicK autokinase activity | Streptococcus mutans serotype c |
F383A/R385A | site-directed mutagenesis, the mutant shows highly reduced autophosphorylation activity compared to the wild-type enzyme | Streptococcus mutans |
F383A/R385A | site-directed mutagenesis, the mutation highly suppresses VicK autokinase activity | Streptococcus mutans serotype c |
I403S | site-directed mutagenesis, the mutation does not significantly affect VicK autokinase activity | Streptococcus mutans serotype c |
I403W | site-directed mutagenesis, the mutation does not significantly affect VicK autokinase activity but dramatically increases autokinase activity in HK853 | Streptococcus mutans serotype c |
K341A/Y342A | site-directed mutagenesis, the mutation negatively affects autokinase activity | Streptococcus mutans serotype c |
additional information | deletion of the first G loop (del392-395, RAQG) negatively affects autokinase activity | Streptococcus mutans serotype c |
N334A/N337A | site-directed mutagenesis, the mutant is nearly as active as the wild-type enzyme in autophosphorylation | Streptococcus mutans |
N334A/N337A | site-directed mutagenesis, the mutation only slightly affects the autokinase activity of the enzyme compared to the wild-type | Streptococcus mutans serotype c |
P222A | site-directed mutagenesis, the mutant abolishes enzyme VicK's phosphatase activity | Streptococcus mutans serotype c |
P222A | site-directed mutagenesis, the mutation eliminates the phosphatase activity of the enzyme | Streptococcus mutans |
P222G | site-directed mutagenesis, the mutant retains full autokinase activity when compared to wild-type, but the mutation abolishes the VicK phosphatase activity | Streptococcus mutans serotype c |
P222G | site-directed mutagenesis, the mutant shows phosphatase activity similar to the wild-type enzyme | Streptococcus mutans |
Q297A/I298A | site-directed mutagenesis, the mutant is nearly as active as the wild-type enzyme in autophosphorylation | Streptococcus mutans |
Q297A/I298A | site-directed mutagenesis, the mutation only slightly affects the autokinase activity of the enzyme compared to the wild-type | Streptococcus mutans serotype c |
R294A | site-directed mutagenesis, the mutant is nearly as active as the wild-type enzyme in autophosphorylation | Streptococcus mutans |
R294A | site-directed mutagenesis, the mutation only slightly affects the autokinase activity of the enzyme compared to the wild-type | Streptococcus mutans serotype c |
R382A/R385A | site-directed mutagenesis, the mutant is inactive in autophosphorylation | Streptococcus mutans |
R382A/R385A | site-directed mutagenesis, the mutant shows highly reduced autophosphorylation activity compared to the wild-type enzyme | Streptococcus mutans |
R382A/R385A | site-directed mutagenesis, the mutation abolishes VicK autokinase activity | Streptococcus mutans serotype c |
R382A/R385A | site-directed mutagenesis, the mutation highly suppresses VicK autokinase activity | Streptococcus mutans serotype c |
T221A | site-directed mutagenesis, the mutant retains full autokinase activity but the enzyme VicK's phosphatase activity is abolished | Streptococcus mutans serotype c |
T221A | site-directed mutagenesis, the mutation eliminates the phosphatase activity but does not affect the autokinase activity of the enzyme | Streptococcus mutans |
T221A/P222A/P222G/V212A/V215A/S213A/S216A | site-directed mutagenesis, the mutation only slightly reduces autokinase activity, while it abolishes the VicK phosphatase activity | Streptococcus mutans serotype c |
V212A/V215A/S213A/S216A | site-directed mutagenesis, the mutation only slightly reduces autokinase activity, while it abolishes the VicK phosphatase activity | Streptococcus mutans serotype c |
Localization | Comment | Organism | GeneOntology No. | Textmining |
---|---|---|---|---|
plasma membrane | VicK has one transmembrane domain, amino acids 9-30, that anchors itself to the cytoplasmic membrane | Streptococcus mutans serotype c | 5886 | - |
Metals/Ions | Comment | Organism | Structure |
---|---|---|---|
Mg2+ | required | Streptococcus mutans |
Molecular Weight [Da] | Molecular Weight Maximum [Da] | Comment | Organism |
---|---|---|---|
103200 | - |
holoenzyme, static light scattering | Streptococcus mutans serotype c |
Natural Substrates | Organism | Comment (Nat. Sub.) | Natural Products | Comment (Nat. Pro.) | Rev. | Reac. |
---|---|---|---|---|---|---|
ATP + protein L-histidine | Streptococcus mutans | - |
ADP + protein N-phospho-L-histidine | - |
? | |
ATP + protein L-histidine | Streptococcus mutans ATCC 700610 | - |
ADP + protein N-phospho-L-histidine | - |
? | |
ATP + VicR L-histidine | Streptococcus mutans | - |
ADP + VicR N-phospho-L-histidine | - |
? | |
ATP + VicR L-histidine | Streptococcus mutans ATCC 700610 | - |
ADP + VicR N-phospho-L-histidine | - |
? |
Organism | UniProt | Comment | Textmining |
---|---|---|---|
Streptococcus mutans | Q8DT64 | - |
- |
Streptococcus mutans ATCC 700610 | Q8DT64 | - |
- |
Streptococcus mutans serotype c | Q8DT64 | - |
- |
Streptococcus mutans serotype c ATCC 700610 | Q8DT64 | - |
- |
Posttranslational Modification | Comment | Organism |
---|---|---|
phosphoprotein | model of VicK autokinase activation, overview | Streptococcus mutans |
Substrates | Comment Substrates | Organism | Products | Comment (Products) | Rev. | Reac. |
---|---|---|---|---|---|---|
ATP + protein L-histidine | - |
Streptococcus mutans | ADP + protein N-phospho-L-histidine | - |
? | |
ATP + protein L-histidine | - |
Streptococcus mutans ATCC 700610 | ADP + protein N-phospho-L-histidine | - |
? | |
ATP + VicR L-histidine | - |
Streptococcus mutans | ADP + VicR N-phospho-L-histidine | - |
? | |
ATP + VicR L-histidine | - |
Streptococcus mutans ATCC 700610 | ADP + VicR N-phospho-L-histidine | - |
? | |
additional information | VicK performs autophosphorylation for self-activation. VicK can also act as a phosphatase dephosphorylating phosphorylated VicR | Streptococcus mutans | ? | - |
? | |
additional information | VicK performs autophosphorylation for self-activation. VicK can also act as a phosphatase dephosphorylating phosphorylated VicR | Streptococcus mutans ATCC 700610 | ? | - |
? |
Subunits | Comment | Organism |
---|---|---|
dimer | the dimeric VicK protein has a rod-shaped structure with the domains linearly connected like beads on a string | Streptococcus mutans |
dimer | the holoenzyme exists as a stable dimer in solution. The overall structure of VicK is a long-rod dimer that anchors four connected domains: HAMP, Per-ARNT-SIM (PAS), DHp, and catalytic and ATP binding domain (CA). The HAMP, a signal transducer, and the PAS domain, major sensor, adopt canonical folds with dyad symmetry. In contrast, the dimer of the DHp and CA domains is asymmetric because of different helical bends in the DHp domain and spatial positions of the CA domains. A conserved proline, which is adjacent to the phosphoryl acceptor histidine, contributes to helical bending, which is essential for the autokinase and phosphatase activities. Following the transmembrane domain, the HAMP signal transducer domain and PAS sensor domain are directly connected to the catalytic domain through a DHp domain, a dimerization and histidine phosphorylation domain. Structure of the HAMP domain (aa 36-86), located at the uppermost position within the N-terminal region of the VicK structure, overview | Streptococcus mutans serotype c |
More | enzyme VicK is composed of several domains (HAMP, PAS, DHp, and catalytic and ATP binding domain [CA]) in addition to a short transmembrane domain. Domain structure-function relationship and analysis, overview. The overall structure of VicK comprises a dimer in the shape of a long slim rod | Streptococcus mutans |
Synonyms | Comment | Organism |
---|---|---|
CovS | UniProt | Streptococcus mutans serotype c |
sensor histidine kinase | - |
Streptococcus mutans |
VicK | - |
Streptococcus mutans |
VicK | - |
Streptococcus mutans serotype c |
VicK-like protein | UniProt | Streptococcus mutans serotype c |
Temperature Optimum [°C] | Temperature Optimum Maximum [°C] | Comment | Organism |
---|---|---|---|
37 | - |
assay at | Streptococcus mutans |
pH Optimum Minimum | pH Optimum Maximum | Comment | Organism |
---|---|---|---|
7.4 | - |
assay at | Streptococcus mutans |
Cofactor | Comment | Organism | Structure |
---|---|---|---|
ATP | - |
Streptococcus mutans |
General Information | Comment | Organism |
---|---|---|
malfunction | mutations in the DHp domain affect kinase activity | Streptococcus mutans |
additional information | conserved proline-222, which is adjacent to the phosphoryl acceptor histidine, contributes to helical bending, which is essential for the autokinase and phosphatase activities. The proline is essential for phosphatase activity. The C-terminal ends of the VicK dimer harbor two monomeric catalytic domains. The enzyme architecture with a signal transducer and sensor domain suggests a model where DHp helical bending and a CA swing movement are likely coordinated for autokinase activation, structure-function analysis, overview | Streptococcus mutans serotype c |
additional information | the VicK kinase activates itself by helical bending of the DHp domain and coordinated swinging around of the catalytic and ATP binding domain to engage with the target histidine. Modelling of the active state structure of the catalytic ATP-binding domain and positioning of inactive domain. Structure-function analysis of the enzyme domains, detailed overview. Transient formation of the active site | Streptococcus mutans |
physiological function | one of the main components of two-component systems, TCSs, is a sensor histidine kinase, which relays extracellular signals to intracellular pathways. VicK is an important sensor histidine kinase in the tooth decay pathogen Streptomyces mutans | Streptococcus mutans |