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Information on EC 2.3.3.10 - hydroxymethylglutaryl-CoA synthase and Organism(s) Enterococcus faecalis and UniProt Accession Q9FD71

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Enterococcus faecalis
UNIPROT: Q9FD71 not found.
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The taxonomic range for the selected organisms is: Enterococcus faecalis
The expected taxonomic range for this enzyme is: Eukaryota, Bacteria, Archaea
Synonyms
hmg-coa, hmg-coa synthase, hmgcs2, hmgs, hmgcs1, 3-hydroxy-3-methylglutaryl-coa synthase, hydroxymethylglutaryl-coa synthase, 3-hydroxy-3-methylglutaryl-coenzyme a synthase, 3-hydroxy-3-methylglutaryl coenzyme a synthase, hmgcs, more
SYNONYM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
HMG-CoA synthase
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(S)-3-hydroxy-3-methylglutaryl-CoA acetoacetyl-CoA-lyase (CoA-acetylating)
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-
-
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3-hydroxy-3-methylglutaryl CoA synthetase
-
-
-
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3-hydroxy-3-methylglutaryl coenzyme A synthase
-
-
-
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3-hydroxy-3-methylglutaryl coenzyme A synthetase
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-
-
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3-hydroxy-3-methylglutaryl-CoA synthase
-
-
-
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3-hydroxy-3-methylglutaryl-coenzyme A synthase
-
-
-
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acetoacetyl coenzyme A transacetase
-
-
-
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beta-hydroxy-beta-methylglutaryl-CoA synthase
-
-
-
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HMG-CoA synthase
-
-
-
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hydroxymethylglutaryl CoA synthetase
-
-
-
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hydroxymethylglutaryl coenzyme A synthase
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-
-
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hydroxymethylglutaryl coenzyme A-condensing enzyme
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-
-
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hydroxymethylglutaryl-coenzyme A synthase
-
-
-
-
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
condensation
-
-
-
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hydrolysis
-
-
-
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Acyl group transfer
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-
-
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transacetylation
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-
-
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SYSTEMATIC NAME
IUBMB Comments
acetyl-CoA:acetoacetyl-CoA C-acetyltransferase (thioester-hydrolysing, carboxymethyl-forming)
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CAS REGISTRY NUMBER
COMMENTARY hide
9027-44-5
-
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
acetyl-CoA + acetoacetyl-CoA + H2O
(S)-3-hydroxy-3-methylglutaryl-CoA + CoA
show the reaction diagram
-
-
-
?
acetyl-CoA + acetoacetyl-CoA + H2O
(S)-3-hydroxy-3-methylglutaryl-CoA + CoA
show the reaction diagram
NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
acetyl-CoA + acetoacetyl-CoA + H2O
(S)-3-hydroxy-3-methylglutaryl-CoA + CoA
show the reaction diagram
-
isopentenyl diphosphate biosynthesis
-
-
ir
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
hymeglusin
i.e. (2E,4E,7R)-11-[(2R,3R)-3-(hydroxymethyl)-4-oxooxetan-2-yl]-3,5,7-trimethylundeca-2,4-dienoic acid, time-dependent loss of activity is observed with more than 95% inhibition achieved at extended incubation times (10 min at 75-600 nM)
acetoacetyl-CoA
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potent inhibitor of the overall reaction
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
MgCl2
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optimal activity in 2.0 mM
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.01
acetoacetyl-CoA
-
-
0.35
acetyl-CoA
-
-
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.7
hymeglusin
in 100 mM Tris-HCl (pH 8.0), at 18°C
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION?
HMGCS_ENTFL
383
0
42151
Swiss-Prot
-
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
42000
-
2 * 42000, calculated from amino acid sequence
45000
-
2 * 45000, SDS-PAGE
83900
-
analytical ultracentrifugation
84300
-
calculated from amino acid sequence
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
dimer
CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
in complex with hymeglusin, hanging drop vapor diffusion method, using 0.1 M Bis-Tris (pH 6.3-6.5), 0.2 M NaCl, and 23% (w/v) polyethylene glycol 3350
mutant A110G. Amide nitrogen of mutants S308 shifts 0.4 A toward the catalytic site cysteine residue stabilizing the intermediate negative charge. The hydroxyl group of S308 rotates to a position where it is able to stabilize the carbanion intermediate of the acetyl-S-enzyme during its condensation with acetoacetyl-CoA
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unliganded and in complex with its second substrate/inhibitor acetoacetyl-CoA. The acetoacetyl-CoA binary structure demonstrates reduced coenzyme A and acetoacetate covalently bound to the active site cysteine through a thioester bond
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PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
A110G
-
overall reaction rate increases 140fold due to adjustments in the active site that result in additional stabilization of all three steps of the reaction pathway. Crystallization data
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
Ni2+-NTA Sepharose column chromatography and Resource Q anion-exchange column chromatography
recombinant enzyme
-
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
expressed in Escherichia coli BL21(DE3) cells
mvaS gene isolated, expressed in Escherichia coli from a pET28 vector
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APPLICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
medicine
-
potential of the mevalonate pathway enzymes of enterococci as targets for antibiotics
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Sutherlin, A.; Hedl, M.; Sanchez-Neri, B.; Burgner, J.W.; Stauffacher, C.V.; Rodwell, V.W.
Enterococcus faecalis 3-hydroxy-3-methylglutaryl coenzyme A synthase, an enzyme of isopentenyl diphosphate biosynthesis
J. Bacteriol.
184
4065-4070
2002
Blattella germanica, Borreliella burgdorferi, Bos taurus, Streptomyces sp., Gallus gallus, Streptococcus pneumoniae, Enterococcus faecalis, Homo sapiens, Mesocricetus auratus, Staphylococcus aureus, Mus musculus, Rattus norvegicus, Staphylococcus epidermidis, Staphylococcus haemolyticus, Streptococcus pyogenes, Sus scrofa
Manually annotated by BRENDA team
Steussy, C.N.; Vartia, A.A.; Burgner, J.W.; Sutherlin, A.; Rodwell, V.W.; Stauffacher, C.V.
X-ray crystal structures of HMG-CoA synthase from Enterococcus faecalis and a complex with its second substrate/inhibitor acetoacetyl-CoA
Biochemistry
44
14256-14267
2005
Enterococcus faecalis
Manually annotated by BRENDA team
Steussy, C.N.; Robison, A.D.; Tetrick, A.M.; Knight, J.T.; Rodwell, V.W.; Stauffacher, C.V.; Sutherlin, A.L.
A structural limitation on enzyme activity: the case of HMG-CoA synthase
Biochemistry
45
14407-14414
2006
Enterococcus faecalis
Manually annotated by BRENDA team
Skaff, D.A.; Ramyar, K.X.; McWhorter, W.J.; Barta, M.L.; Geisbrecht, B.V.; Miziorko, H.M.
Biochemical and structural basis for inhibition of Enterococcus faecalis hydroxymethylglutaryl-CoA synthase, mvaS, by hymeglusin
Biochemistry
51
4713-4722
2012
Enterococcus faecalis (Q9FD71), Enterococcus faecalis
Manually annotated by BRENDA team