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Literature summary for 4.1.3.4 extracted from

  • Montgomery, C.; Pei, Z.; Watkins, P.A.; Miziorko, H.M.
    Identification and characterization of an extramitochondrial human 3-hydroxy-3-methylglutaryl-CoA lyase (2012), J. Biol. Chem., 287, 33227-33236.
    View publication on PubMedView publication on EuropePMC

Cloned(Commentary)

Cloned (Comment) Organism
cloning of 3-hydroxy-3-methylglutaryl-CoA lyase-like protein, sequence comparison of HMGCLL1 and HMGCL, expression of 3-hydroxy-3-methylglutaryl-CoA lyase-like protein mutant G2A in COS-1 cell cytosol, recombinant expression of wild-type 3-hydroxy-3-methylglutaryl-CoA lyase-like protein in Escherichia coli and Pichia pastoris, in insoluble form Homo sapiens
sequence comparison of HMGCLL1 and HMGCL, expression of 3-hydroxy-3-methylglutaryl-CoA lyase wild-type in COS-1 cell cytosol, recombinant expression of wild-type 3-hydroxy-3-methylglutaryl-CoA lyase in Escherichia coli and Pichia pastoris, in active form Homo sapiens

Protein Variants

Protein Variants Comment Organism
C323S site-directed mutagenesis of HMGCL, the mutant shows 2fold increased activity compared to wild-type HMGCL Homo sapiens
G2A site-directed mutagenesis of HMGCLL1, eliminatin of N-terminal myristoylation motif by construction of a 3-hydroxy-3-methylglutaryl-CoA lyase-like protein HMGCLL1 G2A mutant, the mutant shows reduced activity compared to wild-type HMGCLL1 Homo sapiens

KM Value [mM]

KM Value [mM] KM Value Maximum [mM] Substrate Comment Organism Structure
0.024
-
(S)-3-hydroxy-3-methylglutaryl-CoA HMGCLL1 mutant G2A and wild-type HMGCL, pH 8.2, 37°C Homo sapiens
0.024
-
(S)-3-hydroxy-3-methylglutaryl-CoA wild-type HMGCL, pH 8.2, 37°C Homo sapiens
0.028
-
(S)-3-hydroxy-3-methylglutaryl-CoA wild-type HMGCLL1, pH 8.2, 37°C Homo sapiens
0.045
-
(S)-3-hydroxy-3-methylglutaryl-CoA wild-type HMGCLL1, pH 8.2, 37°C Homo sapiens

Localization

Localization Comment Organism GeneOntology No. Textmining
Golgi-derived vesicle endogenous HMGCLL1 localized to punctate vesicles Homo sapiens
-
-
mitochondrion 3-hydroxy-3-methylglutaryl-CoA lyase Homo sapiens 5739
-
additional information HMGCL is a mitochondrial enzyme Homo sapiens
-
-
additional information HMGCLL1 is an extramitochondrial enzyme Homo sapiens
-
-
perinuclear space wild-type 3-hydroxy-3-methylglutaryl-CoA lyase-like protein, myristoylation dependent association with nonmitochondrial membrane compartments Homo sapiens
-
-

Metals/Ions

Metals/Ions Comment Organism Structure
Mg2+ required, Km for wild-type HMGCL is 0.233 mM and for HMGCL mutant C323A 0.322 mM Homo sapiens
Mg2+ required, Km of wild-type HMGCLL1 is 0.049 mM and for HMGCLL1 mutant G2A 0.088 mM Homo sapiens
Mn2+ required, Km for wild-type HMGCL is 0.00034 mM and for HMGCL mutant C323A 0.00037 mM Homo sapiens
Mn2+ required, Km of wild-type HMGCLL1 is 0.00018 mM and for HMGCLL1 mutant G2A 0.00024 mM Homo sapiens

Natural Substrates/ Products (Substrates)

Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
(S)-3-Hydroxy-3-methylglutaryl-CoA Homo sapiens
-
Acetyl-CoA + acetoacetate
-
?

Organism

Organism UniProt Comment Textmining
Homo sapiens
-
-
-

Posttranslational Modification

Posttranslational Modification Comment Organism
lipoprotein the deduced 3-hydroxy-3-methylglutaryl-CoA lyase-like protein, HMGCLL1, sequence contains an N-terminal myristoylation motif. Myristoylation of HMGCLL1 affects its cellular localization Homo sapiens

Purification (Commentary)

Purification (Comment) Organism
recombinant active wild-type 3-hydroxy-3-methylglutaryl-CoA lyase-like protein and its mutant G2A from Pichia pastoris by nickel affinity chromatography and ultrafiltration Homo sapiens

Source Tissue

Source Tissue Comment Organism Textmining
adrenal gland HMGCL Homo sapiens
-
brain cancer cell HMGCLL1 is overexpressed in certain types of human brain cancer cells Homo sapiens
-
cecum HMGCL Homo sapiens
-
duodenum HMGCL Homo sapiens
-
duodenum HMGCLL1 Homo sapiens
-
glioblastoma cell HMGCLL1 Homo sapiens
-
kidney HMGCL Homo sapiens
-
large intestine HMGCL Homo sapiens
-
liver HMGCL Homo sapiens
-
additional information tissue distribution of 3-hydroxy-3-methylglutaryl-CoA lyase, overview Homo sapiens
-
additional information tissue distribution of 3-hydroxy-3-methylglutaryl-CoA lyase-like protein, overview Homo sapiens
-
small intestine HMGCL Homo sapiens
-
small intestine HMGCLL1 Homo sapiens
-
U-87MG cell
-
Homo sapiens
-

Specific Activity [micromol/min/mg]

Specific Activity Minimum [µmol/min/mg] Specific Activity Maximum [µmol/min/mg] Comment Organism
117
-
HMGCLL1 mutant G2A, pH 8.2, 37°C Homo sapiens
150
-
wild-type HMGCLL1, pH 8.2, 37°C Homo sapiens
159
-
wild-type HMGCL, pH 8.2, 37°C Homo sapiens
348
-
HMGCL mutant C323A, pH 8.2, 37°C Homo sapiens

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
(S)-3-Hydroxy-3-methylglutaryl-CoA
-
Homo sapiens Acetyl-CoA + acetoacetate
-
?

Synonyms

Synonyms Comment Organism
3-Hydroxy-3-methylglutaryl-CoA lyase
-
Homo sapiens
3-hydroxy-3-methylglutaryl-CoA lyase-like protein
-
Homo sapiens
HMG-CoA lyase
-
Homo sapiens
HMGCL
-
Homo sapiens
HMGCLL1
-
Homo sapiens

Temperature Optimum [°C]

Temperature Optimum [°C] Temperature Optimum Maximum [°C] Comment Organism
37
-
assay at Homo sapiens

pH Optimum

pH Optimum Minimum pH Optimum Maximum Comment Organism
8.2
-
assay at Homo sapiens