Literature summary for 2.7.1.36 extracted from

Fu, Z.; Voynova, N.E.; Herdendorf, T.J.; Miziorko, H.M.; Kim, J.J.
Biochemical and structural basis for feedback inhibition of mevalonate kinase and isoprenoid metabolism (2008), Biochemistry, 47, 3715-3724.

Cloned(Commentary)

Cloned (Comment)	Organism
expression in Escherichia coli	Homo sapiens
expression in Escherichia coli	Rattus norvegicus

Crystallization (Commentary)

Crystallization (Comment)	Organism
complex with farnesyl thiodiphosphate, 2.5 A resolution. Significant farnesyl thiodiphosphate hydrolysis occurs under crystallization conditions, this results in detection of farnesyl thiophosphate in the structure of the binary complex. Binding sites for these metabolites overlap, with the phosphate of farnesyl thiophosphate nearly superimposed on ATP's phosphate and farnesyl thiophosphate's polyisoprenoid chain overlapping ATPs adenosine moiety	Rattus norvegicus
free enzyme, 2.5 A resolution. Modeling of complex with farnesyl thiophosphate	Homo sapiens

Crystallization (Comment)

Organism

complex with farnesyl thiodiphosphate, 2.5 A resolution. Significant farnesyl thiodiphosphate hydrolysis occurs under crystallization conditions, this results in detection of farnesyl thiophosphate in the structure of the binary complex. Binding sites for these metabolites overlap, with the phosphate of farnesyl thiophosphate nearly superimposed on ATP's phosphate and farnesyl thiophosphate's polyisoprenoid chain overlapping ATPs adenosine moiety

Rattus norvegicus

free enzyme, 2.5 A resolution. Modeling of complex with farnesyl thiophosphate

Homo sapiens

Protein Variants

Protein Variants	Comment	Organism
I196A	modest changes in Km and Ki values	Homo sapiens
I196A	modest changes in Km and Ki values	Rattus norvegicus
I56A	4.5fold increase in Km value for ATP	Homo sapiens
I56A	4.5fold increase in Km value for ATP	Rattus norvegicus
L53A	modest changes in Km and Ki values	Homo sapiens
L53A	modest changes in Km and Ki values	Rattus norvegicus
R388X	modest changes in Km and Ki values	Homo sapiens
R388X	modest changes in Km and Ki values	Rattus norvegicus
T104A	modest changes in Km and Ki values	Homo sapiens
T104A	modest changes in Km and Ki values	Rattus norvegicus
T104A/I196A	39fold increase in Ki value	Homo sapiens
T104A/I196A	39fold increase in Ki value	Rattus norvegicus
T104A/I196A/R388X	11fold increase in Km value for mevalonate	Homo sapiens
T104A/I196A/R388X	11fold increase in Km value for mevalonate	Rattus norvegicus
Y149A	8fold increase in Km value for mevalonate	Homo sapiens
Y149A	8fold increase in Km value for mevalonate	Rattus norvegicus

Inhibitors

Inhibitors	Comment	Organism	Structure
farnesyl diphosphate	feedback regulation	Homo sapiens
farnesyl thiodiphosphate	competitive with ATP, feedback regulation	Rattus norvegicus

KM Value [mM]

KM Value [mM]	KM Value Maximum [mM]	Substrate	Comment	Organism
0.0324	-	(R)-mevalonate	mutant T104A, 30°C, pH 7.5	Homo sapiens
0.0403	-	ATP	mutant T104A, 30°C, pH 7.5	Homo sapiens
0.0408	-	(R)-mevalonate	wild-type, 30°C, pH 7.5	Homo sapiens
0.0459	-	(R)-mevalonate	mutant R388X, 30°C, pH 7.5	Homo sapiens
0.0473	-	(R)-mevalonate	mutant L54A, 30°C, pH 7.5	Homo sapiens
0.0745	-	(R)-mevalonate	mutant T104A/I196A, 30°C, pH 7.5	Homo sapiens
0.1163	-	(R)-mevalonate	mutant I196A, 30°C, pH 7.5	Homo sapiens
0.1784	-	ATP	wild-type, 30°C, pH 7.5	Homo sapiens
0.228	-	(R)-mevalonate	mutant I56A, 30°C, pH 7.5	Homo sapiens
0.2321	-	ATP	mutant L54A, 30°C, pH 7.5	Homo sapiens
0.3018	-	ATP	mutant I196A, 30°C, pH 7.5	Homo sapiens
0.3077	-	ATP	mutant T104A/I196A, 30°C, pH 7.5	Homo sapiens
0.323	-	(R)-mevalonate	mutant Y149A, 30°C, pH 7.5	Homo sapiens
0.3954	-	ATP	mutant T104A/I196A/R388X, 30°C, pH 7.5	Homo sapiens
0.4591	-	(R)-mevalonate	mutant T104A/I196A/R388X, 30°C, pH 7.5	Homo sapiens
0.614	-	ATP	mutant R388X, 30°C, pH 7.5	Homo sapiens
0.6896	-	ATP	mutant Y149A, 30°C, pH 7.5	Homo sapiens
0.8097	-	ATP	mutant I56A, 30°C, pH 7.5	Homo sapiens

Organism

Organism	UniProt	Comment	Textmining
Homo sapiens	Q03426	-	-
Rattus norvegicus	P17256	-	-

Substrates and Products (Substrate)

Substrates	Comment Substrates	Organism	Products	Comment (Products)	Rev.	Reac.
ATP + (R)-mevalonate	-	Homo sapiens	ADP + (R)-5-phosphomevalonate	-	?
ATP + (R)-mevalonate	-	Rattus norvegicus	ADP + (R)-5-phosphomevalonate	-	?

Ki Value [mM]

Ki Value [mM]	Ki Value maximum [mM]	Inhibitor	Comment	Organism
0.000034	-	farnesyl diphosphate	wild-type, 30°C, pH 7.5	Homo sapiens
0.0000553	-	farnesyl diphosphate	mutant I56A, 30°C, pH 7.5	Homo sapiens
0.0000626	-	farnesyl diphosphate	mutant Y149A, 30°C, pH 7.5	Homo sapiens
0.0000734	-	farnesyl diphosphate	mutant L54A, 30°C, pH 7.5	Homo sapiens
0.0000749	-	farnesyl diphosphate	mutant T104A, 30°C, pH 7.5	Homo sapiens
0.0000857	-	farnesyl diphosphate	mutant R388X, 30°C, pH 7.5	Homo sapiens
0.0001807	-	farnesyl diphosphate	mutant I196A, 30°C, pH 7.5	Homo sapiens
0.001313	-	farnesyl diphosphate	mutant T104A/I196A, 30°C, pH 7.5	Homo sapiens
0.001713	-	farnesyl diphosphate	mutant T104A/I196A/R388X, 30°C, pH 7.5	Homo sapiens