Literature summary for 2.3.1.48 extracted from

Kolonko, E.M.; Albaugh, B.N.; Lindner, S.E.; Chen, Y.; Satyshur, K.A.; Arnold, K.M.; Kaufman, P.D.; Keck, J.L.; Denu, J.M.
Catalytic activation of histone acetyltransferase Rtt109 by a histone chaperone (2010), Proc. Natl. Acad. Sci. USA, 107, 20275-20280.

Activating Compound

Activating Compound	Comment	Organism	Structure
VPS75	histone chaperone, acts as activating subunit	Saccharomyces cerevisiae

Crystallization (Commentary)

Crystallization (Comment)	Organism
molecular model of the complex between enzyme Rtt109 and histone chaperone Vps75 based on X-ray diffraction of crystals. The model reveals distinct negative electrostatic surfaces on an Rtt109 molecule that interface with complementary electropositive ends of a symmetrical Vps75 dimer. Rtt109 variants with interface point substitutions lack the ability to be fully activated by Vps75, yet these variants show no adverse effect on Asf1-dependent Rtt109 activities in vitro and in vivo. Molecular model with a 1:2 complex of Rtt109-Vps75 which acetylates a heterodimer of H3-H4	Saccharomyces cerevisiae

Crystallization (Comment)

Organism

molecular model of the complex between enzyme Rtt109 and histone chaperone Vps75 based on X-ray diffraction of crystals. The model reveals distinct negative electrostatic surfaces on an Rtt109 molecule that interface with complementary electropositive ends of a symmetrical Vps75 dimer. Rtt109 variants with interface point substitutions lack the ability to be fully activated by Vps75, yet these variants show no adverse effect on Asf1-dependent Rtt109 activities in vitro and in vivo. Molecular model with a 1:2 complex of Rtt109-Vps75 which acetylates a heterodimer of H3-H4

Saccharomyces cerevisiae

Protein Variants

Protein Variants	Comment	Organism
E299K/E300K/D301K	similar activity toward H3 in comparison to wild-type enzyme, more than 10fold reduction in activation by chaperone Vps75	Saccharomyces cerevisiae
E374A/E378A	similar activity toward H3 in comparison to wild-type enzyme	Saccharomyces cerevisiae
E374K/E378K	similar activity toward H3 in comparison to wild-type enzyme, more than 10fold reduction in activation by chaperone Vps75	Saccharomyces cerevisiae

KM Value [mM]

KM Value [mM]	KM Value Maximum [mM]	Substrate	Comment	Organism
0.0023	-	acetyl-CoA	wild-type, presence of 0.4 equivalents of chaperone Vps75, pH 7.5, 25°C	Saccharomyces cerevisiae
0.0039	-	acetyl-CoA	wild-type, presence of 0.2 equivalents of chaperone Vps75, pH 7.5, 25°C	Saccharomyces cerevisiae
0.0063	-	acetyl-CoA	wild-type, presence of 1 equivalent of chaperone Vps75, pH 7.5, 25°C	Saccharomyces cerevisiae
0.0065	-	acetyl-CoA	wild-type, presence of 2 equivalents of chaperone Vps75, pH 7.5, 25°C	Saccharomyces cerevisiae
0.0065	-	acetyl-CoA	wild-type, presence of 8 equivalents of chaperone Vps75, pH 7.5, 25°C	Saccharomyces cerevisiae

Organism

Organism	UniProt	Comment	Textmining
Saccharomyces cerevisiae	-	-	-

Substrates and Products (Substrate)

Substrates	Comment Substrates	Organism	Products	Comment (Products)	Rev.	Reac.
acetyl-CoA + histone H3	-	Saccharomyces cerevisiae	CoA + acetylhistone H3	-	?
additional information	histone chaperone Vps75 acts as activiating subunit. The rate-determining step of the activated complex is the transfer of the acetyl group from acetyl-CoA to the acceptor lysine residue. Vps75 stimulates catalysis more than 250fold, not by contributing a catalytic base, but by stabilizing the catalytically active conformation of enzyme Rtt109	Saccharomyces cerevisiae	?	-	?

Synonyms

Synonyms	Comment	Organism
Rtt109	-	Saccharomyces cerevisiae

Turnover Number [1/s]

Turnover Number Minimum [1/s]	Turnover Number Maximum [1/s]	Substrate	Comment	Organism
0.0011	-	acetyl-CoA	mutant E374A/E378A/D301K, pH 7.5, 25°C	Saccharomyces cerevisiae
0.0021	-	acetyl-CoA	mutant E374K/E378K, pH 7.5, 25°C	Saccharomyces cerevisiae
0.0023	-	acetyl-CoA	wild-type, pH 7.5, 25°C	Saccharomyces cerevisiae
0.0024	-	acetyl-CoA	mutant E374A/E378A, pH 7.5, 25°C	Saccharomyces cerevisiae
0.031	-	acetyl-CoA	mutant E374A/E378A/D301K, presence of chaperone Vps75, pH 7.5, 25°C	Saccharomyces cerevisiae
0.035	-	acetyl-CoA	mutant E374K/E378K, presence of chaperone Vps75, pH 7.5, 25°C	Saccharomyces cerevisiae
0.07	-	acetyl-CoA	wild-type, wild-type, presence of 0.2 equivalents of chaperone Vps75, pH 7.5, 25°C	Saccharomyces cerevisiae
0.08	-	acetyl-CoA	wild-type, presence of 0.4 equivalents of chaperone Vps75, pH 7.5, 25°C	Saccharomyces cerevisiae
0.16	-	acetyl-CoA	mutant E374A/E378A, presence of chaperone Vps75, pH 7.5, 25°C	Saccharomyces cerevisiae
0.28	-	acetyl-CoA	wild-type, presence of 1 equivalent of chaperone Vps75, pH 7.5, 25°C	Saccharomyces cerevisiae
0.48	-	acetyl-CoA	wild-type, presence of 2 equivalents of chaperone Vps75, pH 7.5, 25°C	Saccharomyces cerevisiae
0.62	-	acetyl-CoA	wild-type, presence of 8 equivalents of chaperone Vps75, pH 7.5, 25°C	Saccharomyces cerevisiae

kcat/KM [mM/s]

kcat/KM Value [1/mMs^-1]	kcat/KM Value Maximum [1/mMs^-1]	Substrate	Comment	Organism
18	-	acetyl-CoA	wild-type, presence of 0.2 equivalents of chaperone Vps75, pH 7.5, 25°C	Saccharomyces cerevisiae
35	-	acetyl-CoA	wild-type, presence of 0.4 equivalents of chaperone Vps75, pH 7.5, 25°C	Saccharomyces cerevisiae
44	-	acetyl-CoA	wild-type, presence of 1 equivalent of chaperone Vps75, pH 7.5, 25°C	Saccharomyces cerevisiae
73	-	acetyl-CoA	wild-type, presence of 2 equivalents of chaperone Vps75, pH 7.5, 25°C	Saccharomyces cerevisiae
97	-	acetyl-CoA	wild-type, presence of 8 equivalents of chaperone Vps75, pH 7.5, 25°C	Saccharomyces cerevisiae