Literature summary for 2.7.13.3 extracted from

Wang, C.; Sang, J.; Wang, J.; Su, M.; Downey, J.S.; Wu, Q.; Wang, S.; Cai, Y.; Xu, X.; Wu, J.; Senadheera, D.B.; Cvitkovitch, D.G.; Chen, L.; Goodman, S.D.; Han, A.
Mechanistic insights revealed by the crystal structure of a histidine kinase with signal transducer and sensor domains (2013), PLoS Biol., 11, e1001493.

Activating Compound

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 (Commentary)

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

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

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

Metals/Ions	Comment	Organism	Structure
Mg2+	required	Streptococcus mutans

Molecular Weight [Da]

Molecular Weight [Da]	Molecular Weight Maximum [Da]	Comment	Organism
103200	-	holoenzyme, static light scattering	Streptococcus mutans serotype c

Natural Substrates/ Products (Substrates)

Natural Substrates	Organism	Comment (Nat. Sub.)	Natural Products	Comment (Nat. Pro.)	Rev.
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

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

Posttranslational Modification	Comment	Organism
phosphoprotein	model of VicK autokinase activation, overview	Streptococcus mutans

Substrates and Products (Substrate)

Substrates	Comment Substrates	Organism	Products	Comment (Products)	Rev.
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

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

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 [°C]	Temperature Optimum Maximum [°C]	Comment	Organism
37	-	assay at	Streptococcus mutans

pH Optimum

pH Optimum Minimum	pH Optimum Maximum	Comment	Organism
7.4	-	assay at	Streptococcus mutans

Cofactor

Cofactor	Comment	Organism	Structure
ATP	-	Streptococcus mutans

General Information

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