Information on EC 5.1.99.4 - alpha-Methylacyl-CoA racemase

Please wait a moment until all data is loaded. This message will disappear when all data is loaded.
Specify your search results
Mark a special word or phrase in this record:
Select one or more organisms in this record:
Show additional data
Do not include text mining results
Include (text mining) results (more...)
Include results (AMENDA + additional results, but less precise; more...)


The expected taxonomic range for this enzyme is: Eukaryota, Bacteria

EC NUMBER
COMMENTARY
5.1.99.4
-
RECOMMENDED NAME
GeneOntology No.
alpha-Methylacyl-CoA racemase
REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
(2S)-2-methylacyl-CoA = (2R)-2-methylacyl-CoA
show the reaction diagram
-
-
-
-
(2S)-2-methylacyl-CoA = (2R)-2-methylacyl-CoA
show the reaction diagram
reaction mechanism, overview, the catalysis of the 1,1-proton transfer by alpha-methyl-acyl-CoA racemase is coupled to a movement of the fatty acyl moiety over a hydrophobic, methionine-rich surface, the mechanism involves the acid/base-pair residues His126 and Asp156, active site geometry, the thioester oxygen atom and the 2-methyl group are in a cisconformation with respect to each other, the thioester oxygen atom fits into an oxyanion hole and the 2-methyl group points into a hydrophobic pocket, Asp127A is a prominent residue in the active site and is located at the bottom of the catalytic site
O06543
REACTION TYPE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
racemization
-
-
-
-
PATHWAY
KEGG Link
MetaCyc Link
bile acid biosynthesis, neutral pathway
-
Metabolic pathways
-
Primary bile acid biosynthesis
-
SYSTEMATIC NAME
IUBMB Comments
2-Methylacyl-CoA 2-epimerase
alpha-methyl-branched acyl-CoA derivatives with chain lengths of more than C10 are substrates. Also active towards some aromatic compounds (e.g. ibuprofen) and bile acid intermediates, such as trihydroxycoprostanoyl-CoA. Not active towards free acids
SYNONYMS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
2-arylpropionyl-CoA epimerase
-
-
-
-
2-methylacyl-CoA racemase
-
-
-
-
alpha-methyl CoA racemase
-
-
alpha-Methylacyl CoA racemase
-
-
-
-
alpha-Methylacyl CoA racemase
-
-
alpha-methylacyl coenzyme A racemase
-
-
alpha-methylacyl coenzyme A racemase
Q9UHK6
-
alpha-methylacyl coenzyme A racemase
-
-
alpha-methylacyl-CoA racemase
Q9UHK6
-
alpha-methylacyl-CoA racemase
-
-
alpha-methylacyl-CoA racemase 1A
-
-
alpha-methylacyl-coenzyme A racemase
-
-
alpha-methylacyl-coenzyme A racemase
-
-
AMACR
B3KMU8
-
AMACR
Q3KT79
-
AMACR
Q6VRU3, Q6VRU4
-
AMACR 1A
-
-
amacr/P504S
-
-
GenBank U89905-derived protein GI2145184
-
-
-
-
GenBank U89906-derived protein GI 2145186
-
-
-
-
ibuprofenoyl-CoA epimerase
-
-
P504S
Q9UHK6
-
Racemase, alpha-methylacyl coenzyme A
-
-
-
-
Racemase, alpha-methylacyl coenzyme A (Mus musculus clone 3)
-
-
-
-
Racemase, alpha-methylacyl coenzyme A (Rattus norvegicus clone 11)
-
-
-
-
CAS REGISTRY NUMBER
COMMENTARY
156681-44-6
-
197731-71-8
racemase, alpha-methylacyl coenzyme A (Mus musculus clone 3) /genBank U89906-derived protein GI 2145186
197731-72-9
racemase, alpha-methylacyl coenzyme A (Rattus norvegicus clone 11) /genBank U89905-derived protein GI2145184
ORGANISM
COMMENTARY
LITERATURE
SEQUENCE CODE
SEQUENCE DB
SOURCE
-
Q3KT79
SwissProt
Manually annotated by BRENDA team
isoenzyme IA; isoenzyme IB
SwissProt
Manually annotated by BRENDA team
isoenzyme IIA
UniProt
Manually annotated by BRENDA team
isoenzyme IIAs
SwissProt
Manually annotated by BRENDA team
isoenzyme IIB
SwissProt
Manually annotated by BRENDA team
patients with early Barrett's adenocarcinoma treated with surgery
-
-
Manually annotated by BRENDA team
patients with gastric intestinal-type adenocarcinoma and its precursors
-
-
Manually annotated by BRENDA team
patients with noninvasive bladder cancer
-
-
Manually annotated by BRENDA team
strain P101
-
-
Manually annotated by BRENDA team
strain P101
-
-
Manually annotated by BRENDA team
GENERAL INFORMATION
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
malfunction
-
alpha-methylacyl coenzyme A racemase is positive in most cancers and dysplasias but only rarely in nonneoplastic epithelium
metabolism
-
beta-oxidation pathway of fatty acids
metabolism
-
beta-oxidation of branched-chain fatty acids, important enzyme for the metabolism of branched-chain lipids and drugs
physiological function
-
enzyme catalyzes the 1,1-proton transfer reaction that effects the reversible epimerization of the coenzyme A thioesters derived from a variety of (2R)- and (2S)-methyl branched fatty acids
physiological function
-
enzyme is involved in the beta-oxidation of branched-chain fatty acids
physiological function
-
alpha-methylacyl-CoA racemase is a protein that plays an important role in mitochondrial and peroxisomal beta-oxidation of branched-chain fatty acid and bile acid intermediates
physiological function
-
enzyme catalyzes the racemization of alpha-methyl carboxylic coenzyme A thioesters in mitochondria and peroxisomes, induction of AMACR-specific cytotoxic mononuclear cells from prostate cancer patients peripheral blood mononuclear cells
physiological function
-
alpha-methylacyl-CoA racemase catalyses the inversion of configuration at the 2-position of fatty acyl-CoA esters from 2R to 2S and controls entry of metabolites into peroxisomal beta-oxidation
SUBSTRATE
PRODUCT                      
REACTION DIAGRAM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
(Substrate)
LITERATURE
(Substrate)
COMMENTARY
(Product)
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
(25S)-3,7,12-trihydroxycoprostanoic acid
(25R)-3,7,12-trihydroxycoprostanoic acid
show the reaction diagram
O06543
-
-
-
r
(25S)-trihydroxycoprostanoyl-CoA
(25R)-trihydroxycoprostanoyl-CoA
show the reaction diagram
-
-
-
-
?
(2R)-ibuprofenoyl-CoA
(2S)-ibuprofenoyl-CoA
show the reaction diagram
-
-
-
-
r
(2R)-pristanoyl-CoA
(2S)-pristanoyl-CoA
show the reaction diagram
-
-
-
-
r
(2S)-2-methylacyl-CoA
(2R)-2-methylacyl-CoA
show the reaction diagram
-
-
-
-
?
(2S)-2-methylacyl-CoA
(2R)-2-methylacyl-CoA
show the reaction diagram
-
-
-
-
r
(2S)-2-methylacyl-CoA
(2R)-2-methylacyl-CoA
show the reaction diagram
-
-
-
-
?
(2S)-2-methylacyl-CoA
(2R)-2-methylacyl-CoA
show the reaction diagram
O06543
-
-
-
r
(2S)-2-methylacyl-CoA
(2R)-2-methylacyl-CoA
show the reaction diagram
-
natural substrates are branched chain alpha-methylacyl coenzyme A esters
-
-
?
(2S)-2-methylacyl-CoA
(2R)-2-methylacyl-CoA
show the reaction diagram
-
the enzyme plays an important role in peroxisomal beta-oxidation of branched-chain fatty acids from red meat and dairy products, the enzyme is a biomarker overexpressed in prostate carcinomas and is associated with prostate cancer progression
-
-
r
(2S)-2-methylacyl-CoA
(2R)-2-methylacyl-CoA
show the reaction diagram
O06543
substrate binding structure, the S-substrate and the R-substrate bind in an S-pocket and an R-pocket, respectively, the enzyme contains a large number of methionine residues in the acyl binding region, located between the S-pocket and the R-pocket, overview
-
-
r
(R)-2-methyldecanoyl-CoA
(S)-2-methyldecanoyl-CoA
show the reaction diagram
-
-
-
-
r
(R)-2-methylpentadecanoyl-CoA
(S)-2-methylpentadecanoyl-CoA
show the reaction diagram
-
-
-
-
?
(R)-2-methyltetradecanoyl-CoA
(S)-2-methyltetradecanoyl-CoA
show the reaction diagram
-
-
-
-
r
(R)-fenoprofenoyl-CoA
(S)-fenoprofenoyl-CoA
show the reaction diagram
-
best substrate
-
-
?
(R)-ibuprofenoyl-CoA
(S)-ibuprofenoyl-CoA
show the reaction diagram
-
-
-
-
?
(R)-ibuprofenoyl-CoA
(S)-ibuprofenoyl-CoA
show the reaction diagram
-
-
-
-
r
(R)-pristanoyl-CoA
(S)-pristanoyl-CoA
show the reaction diagram
-
-
-
-
?
(R)-pristanoyl-CoA
(S)-pristanoyl-CoA
show the reaction diagram
-
-
-
-
r
(R)-pristanoyl-CoA
(S)-pristanoyl-CoA
show the reaction diagram
-
-
-
-
?
(S)-2-methyldecanoyl-CoA
(R)-2-methyldecanoyl-CoA
show the reaction diagram
-
-
-
-
r
(S)-2-Methylmyristoyl-CoA
(R)-2-Methylmyristoyl-CoA
show the reaction diagram
-
-
-
-
?
(S)-2-Methylmyristoyl-CoA
(R)-2-Methylmyristoyl-CoA
show the reaction diagram
-
r
-
-
-
(S)-2-Methyltetradecanoyl-CoA
(R)-2-Methyltetradecanoyl-CoA
show the reaction diagram
-
r
-
-
-
(S)-ibuprofenoyl-CoA
(R)-ibuprofenoyl-CoA
show the reaction diagram
O06543
binding mode at the active site, binding structure, overview
-
-
r
(S)-ketoprofenoyl-CoA
(R)-ketoprofenoyl-CoA
show the reaction diagram
-
-
-
-
?
(S)-methyldecanoyl-CoA
(R)-methyldecanoyl-CoA
show the reaction diagram
-
-
-
-
?
(S)-naproxenoyl-CoA
(R)-naproxenoyl-CoA
show the reaction diagram
-
-
-
-
?
(S)-Pristanoyl-CoA
(R)-Pristanoyl-CoA
show the reaction diagram
-
-
-
-
-
(S)-Pristanoyl-CoA
(R)-Pristanoyl-CoA
show the reaction diagram
-
-
-
-
?
(S)-Pristanoyl-CoA
(R)-Pristanoyl-CoA
show the reaction diagram
O06543
-
-
-
r
(S)-Pristanoyl-CoA
(R)-Pristanoyl-CoA
show the reaction diagram
-
r
-
-
-
(S)-Trihydroxycoprostanoyl-CoA
(R)-Trihydroxycoprostanoyl-CoA
show the reaction diagram
-
-
-
-
-
(S)-Trihydroxycoprostanoyl-CoA
(R)-Trihydroxycoprostanoyl-CoA
show the reaction diagram
-
r
-
-
-
3alpha,7alpha,12alpha-trihydroxy-5beta-cholestanoyl-CoA
?
show the reaction diagram
-
-
-
-
?
S-[(2R)-2-methyl-6-[(3alpha,5beta,7alpha)-3,7,12-trihydroxy-10-methylgonan-17-yl]heptanoyl]-CoA
S-[(2S)-2-methyl-6-[(3alpha,5beta,7alpha)-3,7,12-trihydroxy-10-methylgonan-17-yl]heptanoyl]-CoA
show the reaction diagram
-
-
-
-
r
flurbiprofenoyl-CoA
?
show the reaction diagram
-
-
-
-
?
additional information
?
-
-
-
-
-
-
additional information
?
-
-
no activity with free fatty acids
-
-
-
additional information
?
-
-
no activity with 3-methyl-branched or linear-chain acyl-CoAs
-
-
-
additional information
?
-
-
enzyme is involved in the alternative pathway of cholesterol side-chain oxidation. The alternative pathway consists of alpha-methylacyl-CoA racemase, and peroxisomal multifunctional enzyme type 1 (peroxisomal multifunctional 2-enoyl-CoA hydratase/(S)-3-hydroxyacyl-CoA dehydrogenase)
-
?
additional information
?
-
-
key enzyme in the metabolism of 2-methyl-branched fatty acids
-
?
additional information
?
-
-
enzyme expression is increased in extramammary Paget disease, EMPD, overview
-
-
-
additional information
?
-
-
the enzyme can distinguish hepatocellular carcinoma and dysplastic hepatocytes from benign nondysplastic hepatocytes, overview
-
-
-
additional information
?
-
-
the enzyme is essential for the beta-oxidation of bile acid intermediates and branched-chain fatty acids
-
-
-
additional information
?
-
-
the enzyme is involved in gastrointestinal malgnancies
-
-
-
additional information
?
-
-
the enzyme is involved in metabolism of branched-chain fatty acids, expression of AMACR in colorectal carcinoma is correlated with tumor differentiation, overview
-
-
-
additional information
?
-
-
the enzyme prepares branched chain fatty acids to be metabolized for energy and is implicated in the activation of the COX-inhibiting form of ibuprofen
-
-
-
additional information
?
-
-
the risk of familial, but not sporadic, prostate cancer may be associated with germline variation in the AMACR gene, overview
-
-
-
additional information
?
-
O06543
structure of the enzyme in complex with acetyl-CoA, acetoacetyl-CoA, (R,S)-ibuprofenoyl-CoA, (2S)-methylmyristoyl-CoA, or (2R)-methylmyristoyl-CoA, overview
-
-
-
additional information
?
-
-
the enzyme catalyzes the racemization of alpha-methyl, branched carboxylic coenzyme A thioesters
-
-
-
NATURAL SUBSTRATES
NATURAL PRODUCTS
REACTION DIAGRAM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
(Substrate)
LITERATURE
(Substrate)
COMMENTARY
(Product)
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
(2S)-2-methylacyl-CoA
(2R)-2-methylacyl-CoA
show the reaction diagram
-
-
-
-
?
(2S)-2-methylacyl-CoA
(2R)-2-methylacyl-CoA
show the reaction diagram
O06543
-
-
-
r
(2S)-2-methylacyl-CoA
(2R)-2-methylacyl-CoA
show the reaction diagram
-
natural substrates are branched chain alpha-methylacyl coenzyme A esters
-
-
?
(2S)-2-methylacyl-CoA
(2R)-2-methylacyl-CoA
show the reaction diagram
-
the enzyme plays an important role in peroxisomal beta-oxidation of branched-chain fatty acids from red meat and dairy products, the enzyme is a biomarker overexpressed in prostate carcinomas and is associated with prostate cancer progression
-
-
r
additional information
?
-
-
enzyme expression is increased in extramammary Paget disease, EMPD, overview
-
-
-
additional information
?
-
-
the enzyme can distinguish hepatocellular carcinoma and dysplastic hepatocytes from benign nondysplastic hepatocytes, overview
-
-
-
additional information
?
-
-
the enzyme is essential for the beta-oxidation of bile acid intermediates and branched-chain fatty acids
-
-
-
additional information
?
-
-
the enzyme is involved in gastrointestinal malgnancies
-
-
-
additional information
?
-
-
the enzyme is involved in metabolism of branched-chain fatty acids, expression of AMACR in colorectal carcinoma is correlated with tumor differentiation, overview
-
-
-
additional information
?
-
-
the enzyme prepares branched chain fatty acids to be metabolized for energy and is implicated in the activation of the COX-inhibiting form of ibuprofen
-
-
-
additional information
?
-
-
the risk of familial, but not sporadic, prostate cancer may be associated with germline variation in the AMACR gene, overview
-
-
-
INHIBITORS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
(24S,25R)-(3R,7R,12R)-trihydroxy-24-fluoro-5beta-cholestan-26-oyl-CoA
-
competitive inhibition
(25-R,S)-3,7,12-trihydroxycoprostanoic acid
O06543
competitive inhibition
(2R)-ibuprofenoyl-CoA
-
competitive inhibitor
(2R,3S)-3-fluoro-2-methylhexadecanoyl-CoA
-
competitive inhibition
(2S)-ibuprofenoyl-CoA
-
competitive inhibitor
(2S,3R)-3-fluoro-2-methylhexadecanoyl-CoA
-
competitive inhibition
(R)-2-methylmyristoyl CoA
O06543
binding mode
(R)-ibuprofenoyl-CoA
-
competitive inhibition
(R,S)-ibuprofenoyl-CoA
O06543
competitive inhibition
(S)-2-methylmyristoyl CoA
O06543
binding mode
(S)-ibuprofenoyl-CoA
-
competitive inhibition
(S)-ibuprofenoyl-CoA
O06543
competitive inhibition
1-ethyl-3-(3-dimethylaminopropyl)-carbodiimide
-
-
2-(4-Isobutylphenyl)propionic acid
-
i.e. ibuprofen, strongest of all competitive inhibitors tested
2-(4-Isobutylphenyl)propionic acid
-
-
2-difluoromethylpentadecanoyl-CoA
-
competitive inhibition
2-methylmyristoyl CoA
-
competitive inhibition
2-methylmyristoyl-CoA
-
inhibits reaction with 2-pristanoyl-CoA
2-methylmyristoyl-CoA
-
-
2-methyloctanoyl CoA
-
competitive inhibition
2-methyloctanoyl-CoA
-
inhibits reaction with 2-pristanoyl-CoA
2-methyloctanoyl-CoA
-
-
2-trifluoromethyltetradecanoic acid
-
competitive inhibition
2-trifluoromethyltetradecanoyl-CoA
-
competitive inhibition
5,5'-dithiobis(2-nitrobenzoate)
-
inhibition is reversed by incubation of the inactivated enzyme with 10 mM dithiothreitol
acetoacetyl-CoA
O06543
-
alpha-trifluoromethyltetradecanoic acid
-
inhibits growth of cancer cell lines PC3, CWR22 Rv1, and Du145 in a dose-dependent manner due to AMACR inhibition
beta-fluorinated branched chain alpha-methylacyl coenzyme A esters analogues
-
reversible competitive inhibitors, presence of beta-fluorine on the alpha-methyl group or the acyl chain results in a significant lowering of the Ki value compared with nonfluorinated analogs, and this is attributed to a lowering of the pKa of the alpha-proton, facilitating enolization and binding, competitive
-
Decanoyl-CoA
-
non-competitive substrate inhibition at higher substrate concentrations
Diethylpyrocarbonate
-
-
diisopropylphosphofluoridate
-
-
Fe2+
-
slight inhibition
-
octyl-beta-D-glucopyranoside
-
concentrations greater than 0.6% octyl-beta-D-glucopyranoside cause a reduction in enzyme activity
palmitoyl-CoA
-
stimulates at low concentrations, inhibits above 0.1 mM
palmitoyl-CoA
-
inhibition is caused by the formation of stable mixed micelles
palmitoyl-CoA
-
-
thimerosal
-
slight
Ibuprofen
-
chemopreventive effects of ibuprofen on prostate cancer risk, which may be enhanced by AMACR genetic variants
additional information
-
no inhibition by iodoacetamide
-
additional information
-
design of mechanism-based irreversible inhibitors, 2-methylmyrist-2-enoyl CoA is not an inhibitor, mechanism, overview
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
palmitoyl-CoA
-
stimulates at low concentrations, inhibits above 0.1 mM
KM VALUE [mM]
KM VALUE [mM] Maximum
SUBSTRATE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
0.048
-
(2R)-ibuprofenoyl-CoA
-
recombinant enzyme, 50 mM Tris-HCl, 0.2% octyl-beta-D-glucopyranoside, pH 8.0 at 37C
0.071
-
(2R)-ibuprofenoyl-CoA
-
recombinant six-His tagged enzyme, 50 mM Tris-HCl, 0.2% octyl-beta-D-glucopyranoside, pH 8.0 at 37C
0.086
-
(2S)-ibuprofenoyl-CoA
-
recombinant enzyme, 50 mM Tris-HCl, 0.2% octyl-beta-D-glucopyranoside, pH 8.0 at 37C
0.087
-
(2S)-ibuprofenoyl-CoA
-
recombinant six-His tagged enzyme, 50 mM Tris-HCl, 0.2% octyl-beta-D-glucopyranoside, pH 8.0 at 37C
1.2
-
(R)-2-methyldecanoyl-CoA
-
recombinant enzyme, 50 mM NaH2PO4-NaOH, pH 7.2
0.041
-
(R)-Pristanoyl-CoA
-
wild type
0.614
-
(S)-2-methyldecanoyl-CoA
-
pH and temperature not specified in the publication
1.2
-
(S)-2-methyldecanoyl-CoA
-
recombinant enzyme, 50 mM NaH2PO4-NaOH, pH 7.2
0.052
-
(S)-ketoprofenoyl-CoA
-
pH and temperature not specified in the publication
-
0.277
-
(S)-methyldecanoyl-CoA
-
pH and temperature not specified in the publication
-
0.076
-
pristanoyl-CoA
-
-
0.172
-
pristanoyl-CoA
-
-
0.0316
-
trihydroxycoprostanoyl-CoA
-
-
0.06
-
trihydroxycoprostanoyl-CoA
-
-
0.068
-
(S)-naproxenoyl-CoA
-
pH and temperature not specified in the publication
-
additional information
-
additional information
-
similar Km values for mutants H126A, D156A and E241A as for the wild-type
-
TURNOVER NUMBER [1/s]
TURNOVER NUMBER MAXIMUM[1/s]
SUBSTRATE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
228
-
(2R)-ibuprofenoyl-CoA
-
recombinant six-His tagged enzyme, 50 mM Tris-HCl, 0.2% octyl-beta-D-glucopyranoside, pH 8.0 at 37C
291
-
(2R)-ibuprofenoyl-CoA
-
recombinant enzyme, 50 mM Tris-HCl, 0.2% octyl-beta-D-glucopyranoside, pH 8.0 at 37C
358
-
(2S)-ibuprofenoyl-CoA
-
recombinant six-His tagged enzyme, 50 mM Tris-HCl, 0.2% octyl-beta-D-glucopyranoside, pH 8.0 at 37C
450
-
(2S)-ibuprofenoyl-CoA
-
recombinant enzyme, 50 mM Tris-HCl, 0.2% octyl-beta-D-glucopyranoside, pH 8.0 at 37C
53.8
-
(R)-2-methyldecanoyl-CoA
-
recombinant enzyme, 50 mM NaH2PO4-NaOH, pH 7.2
0.07
-
(S)-2-methyldecanoyl-CoA
-
pH and temperature not specified in the publication
60.9
-
(S)-2-methyldecanoyl-CoA
-
recombinant enzyme, 50 mM NaH2PO4-NaOH, pH 7.2
0.015
-
(S)-ketoprofenoyl-CoA
-
pH and temperature not specified in the publication
-
0.031
-
(S)-methyldecanoyl-CoA
-
pH and temperature not specified in the publication
-
0.0095
-
(S)-naproxenoyl-CoA
-
pH and temperature not specified in the publication
-
kcat/KM VALUE [1/mMs-1]
kcat/KM VALUE [1/mMs-1] Maximum
SUBSTRATE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
0.0032
-
(2R)-ibuprofenoyl-CoA
-
recombinant six-His tagged enzyme, 50 mM Tris-HCl, 0.2% octyl-beta-D-glucopyranoside, pH 8.0 at 37C
292436
0.0061
-
(2R)-ibuprofenoyl-CoA
-
recombinant enzyme, 50 mM Tris-HCl, 0.2% octyl-beta-D-glucopyranoside, pH 8.0 at 37C
292436
0.0041
-
(2S)-ibuprofenoyl-CoA
-
recombinant six-His tagged enzyme, 50 mM Tris-HCl, 0.2% octyl-beta-D-glucopyranoside, pH 8.0 at 37C
292437
0.0052
-
(2S)-ibuprofenoyl-CoA
-
recombinant enzyme, 50 mM Tris-HCl, 0.2% octyl-beta-D-glucopyranoside, pH 8.0 at 37C
292437
44.8
-
(R)-2-methyldecanoyl-CoA
-
recombinant enzyme, 50 mM NaH2PO4-NaOH, pH 7.2
293339
0.114
-
(S)-2-methyldecanoyl-CoA
-
pH and temperature not specified in the publication
293338
50.75
-
(S)-2-methyldecanoyl-CoA
-
recombinant enzyme, 50 mM NaH2PO4-NaOH, pH 7.2
293338
0.29
-
(S)-ketoprofenoyl-CoA
-
pH and temperature not specified in the publication
0
0.112
-
(S)-methyldecanoyl-CoA
-
pH and temperature not specified in the publication
0
0.14
-
(S)-naproxenoyl-CoA
-
pH and temperature not specified in the publication
0
additional information
-
additional information
-
Mycobacterium tuberculosis enzyme expressed as a fusion protein bearing an N-terminal six-His tag has a catalytic efficiency that is reduced 22% and 47% in the 2S-2R and 2R-2S directions, respectively, relative to untagged enzyme
0
Ki VALUE [mM]
Ki VALUE [mM] Maximum
INHIBITOR
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
0.0038
-
(24S,25R)-(3R,7R,12R)-trihydroxy-24-fluoro-5beta-cholestan-26-oyl-CoA
-
pH 7.0, 37C
0.0013
-
(2R,3S)-3-fluoro-2-methylhexadecanoyl-CoA
-
pH 7.0, 37C
0.0023
-
(2S,3R)-3-fluoro-2-methylhexadecanoyl-CoA
-
pH 7.0, 37C
0.0054
-
(R)-ibuprofenoyl-CoA
-
pH 7.0, 37C
0.0192
-
(S)-ibuprofenoyl-CoA
-
pH 7.0, 37C
0.02
-
2-difluoromethylpentadecanoyl-CoA
-
pH 7.0, 37C
0.137
-
2-methylmyristoyl CoA
-
pH 7.0, 37C
0.045
-
2-methyloctanoyl CoA
-
pH 7.0, 37C
0.0009
-
2-trifluoromethyltetradecanoyl-CoA
-
pH 7.0, 37C
additional information
-
additional information
-
inhibition kinetics
-
SPECIFIC ACTIVITY [µmol/min/mg]
SPECIFIC ACTIVITY MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
0.21
-
-
mutant P1
68.4
-
-
substrate is (R)-2-methyldecanoyl-CoA, recombinant enzyme, 50 mM NaH2PO4-NaOH, pH 7.2
77.5
-
-
substrate is (S)-2-methyldecanoyl-CoA, recombinant enzyme, 50 mM NaH2PO4-NaOH, pH 7.2
additional information
-
-
development of a very sensitive and convenient radiometric assay
additional information
-
-
development of a coupled assay based on the use of pristanoyl-CoA oxidase/peroxidase
additional information
-
-
elevated enzyme activity in cancer tissues
additional information
-
-
Vmax 214 units/mg wild-type, less than 0.1 unit/mg mutants H126A, D156A and E241A
pH OPTIMUM
pH MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
6
-
-
pristanoyl-CoA
7
-
-
trihydroxycoprostanoyl-CoA
7
-
-
assay at
8
-
-
-
8
-
O06543
assay at
pH RANGE
pH RANGE MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
6.5
9
-
more than 80% of maximal activity between pH 6.5 and pH 9.0, inactive below pH 5
TEMPERATURE OPTIMUM
TEMPERATURE OPTIMUM MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
37
-
-
assay at
37
-
O06543
assay at
pI VALUE
pI VALUE MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
6.07
-
B3KMU8, Q6VRU3, Q6VRU4, Q9UHK6
isoenzyme IA, calculated
7.01
-
Q3KT79
calculated
9.44
-
B3KMU8, Q6VRU3, Q6VRU4, Q9UHK6
isoenzyme IIB, calculated
9.62
-
B3KMU8, Q6VRU3, Q6VRU4, Q9UHK6
isoenzyme IIA, calculated
9.65
-
B3KMU8, Q6VRU3, Q6VRU4, Q9UHK6
isoenzyme IIAs, calculated
10.31
-
B3KMU8, Q6VRU3, Q6VRU4, Q9UHK6
isoenzyme IB, calculated
SOURCE TISSUE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
SOURCE
-
immunohistochemic detection
Manually annotated by BRENDA team
-
epithelium that is negative for dysplasia and columnar epithelial cell changes indefinite for dysplasia does not demonstrate immunoreactivity for alpha-methylacyl-Coa racemase. Barrett's epithelium with columnar epithelial cell changes indefinite for dysplasia demonstrates alpha-methylacyl-Coa racemase immunoreactivity in 30% of cases
Manually annotated by BRENDA team
-
dysplastic Barretts epithelium, immunohistochemic detection
Manually annotated by BRENDA team
-
upper urinary tract urothelial carcinomas
Manually annotated by BRENDA team
-
immunohistochemic detection
Manually annotated by BRENDA team
-
patients with chronic inflammatory disease prostate carcinoma
Manually annotated by BRENDA team
-
histologic and expression analysis in different samples, primary and metastatic colorectal carcinoma, overview
Manually annotated by BRENDA team
-
differential enzyme expression, overexpression and correlation with tumor pathologic features, immunohistochemic analysis, overview
Manually annotated by BRENDA team
-
prostate cancer cell line
Manually annotated by BRENDA team
-
dysplastic Barretts epithelium, immunohistochemic detection
Manually annotated by BRENDA team
-
staining for alpha-methylacyl-CoA racemase is uniformly negative in samples negative for dysplasia and indefinite for dysplasia. In the groups of high-grade dysplasia and invasive intestinal-type adenocarcinoma, 76% and 34% of samples are positive for alpha-methylacyl-CoA racemase, respectively. Expression of alpha-methylacyl-CoA racemase is not correlated with location, Helicobacter pylori infection, or intestinal metaplasia
Manually annotated by BRENDA team
-
immunohistochemic detection and expression analysis, pattern and distribution, overview
Manually annotated by BRENDA team
-
in proximal convoluted renal tubules, no expression in minimal distal tubules, glomeruli, medullary tubules, and stromal cells
Manually annotated by BRENDA team
-
nonysplastic liver tissue, immunohistochemic detection and expression analysis, pattern and distribution, overview
Manually annotated by BRENDA team
-
prostate cancer cell line
Manually annotated by BRENDA team
-
prostate cancer cell line
Manually annotated by BRENDA team
-
higher expression in Prostatic intraepithelial neoplasia, lower in atypia and carcinoma, possibility of detecting small focal prostatic cancer, prostatic adenocarcinoma, by AMACR immunohistochemistry on needle biopsy specimens with high sensitivity, overview
Manually annotated by BRENDA team
-
enzyme overexpression in prostate cancer and its precursor lesions, differences in AMACR allele frequencies, overview
Manually annotated by BRENDA team
-
acinal cells, analysis of downregulating effects of hormone therapy on enzyme expression, immunohistochemic analysis, no expression in tumor cells in 29%, overview
Manually annotated by BRENDA team
-
overexpression of the enzyme compared to healthy prostate gland
Manually annotated by BRENDA team
-
high grade prostatic intraepithelial neoplasia
Manually annotated by BRENDA team
-
from healthy persons, and after cystoprostatectomy and radical prostatectomy, overview, enzyme activity in prostate is increased from normal looking epithelial cells and atrophy, to prostatic intraepithelial neoplasia, away from and adjacent to prostate carcinoma, the expression in prostate carcinoma is slightly lower in cystoprostatectomy compared to radical prostatectomy specimen, immunohistochemic detection, overview
Manually annotated by BRENDA team
-
low expression level
Manually annotated by BRENDA team
-
from patients with prostate carcinoma, atypia and benign hyperplasia
Manually annotated by BRENDA team
-
type 1 and type 2 papillary, conventional, and chromophobe renal cell carcinoma, oncocytomas, mucinous tubular and spindle tumors, urothelial carcinomas, angiomyolipomas, and Bellini carcinomas, immunohistochemical analysis of enzyme expression, overview
Manually annotated by BRENDA team
-
samples of normal adult glands as well as cases of sebaceous hyperplasia, sebaceous adenoma, and basal cell carcinoma with sebaceous differentiation and extraocular sebaceous carcinoma
Manually annotated by BRENDA team
-
patients with AMACR-positive SCLC show a better survival rate
Manually annotated by BRENDA team
-
adenocarcinoma, dysplasia and non-neoplastic epithelium of the stomach, expression analysis, overview
Manually annotated by BRENDA team
-
from a renal neoplasm
Manually annotated by BRENDA team
additional information
-
enzyme expression is increased in extramammary Paget disease, EMPD, in women and men, immunohistochemic detection, overview
Manually annotated by BRENDA team
additional information
-
high-grade tumor tissue expression analysis and clinical characteristics, but different levels of expression have no correlation with survival for any tumor type, overview
Manually annotated by BRENDA team
additional information
-
no expression in healthy colon epithelium, the enzyme immunoreactivity is highly specific in distinguishing high-grade dysplasia from reactive atypia, but only moderately specific for identification of high-grade dysplasia in Barrett's esophagus, overview
Manually annotated by BRENDA team
additional information
-
enzyme expression is increased in renal tumors compared to healthy kidney tissue
Manually annotated by BRENDA team
additional information
-
no expression in benign prostate gland and acinar cells
Manually annotated by BRENDA team
additional information
-
immunohistochemic analysis, the enzyme is overexpressed in cancer tissue, such as breast, colorectal and ovarian cancers, no expression in epithelial type Wilms tumor
Manually annotated by BRENDA team
additional information
-
borderline tumors do not show any AMACR expression
Manually annotated by BRENDA team
LOCALIZATION
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
-
diffuse cytoplasmic distribution dependent on the liver tissue type, overview
Manually annotated by BRENDA team
-
coarsely granular distribution dependent on the liver tissue type, overview
Manually annotated by BRENDA team
-
only 10-30% of the activity is found in mitochondria
Manually annotated by BRENDA team
-
co-distributed exclusively with mitochondrial marker enzymes
Manually annotated by BRENDA team
MOLECULAR WEIGHT
MOLECULAR WEIGHT MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
22200
-
B3KMU8, Q6VRU3, Q6VRU4, Q9UHK6
isoenzyme IB, calculated
28470
-
B3KMU8, Q6VRU3, Q6VRU4, Q9UHK6
isoenzyme IIAs, calculated
30790
-
B3KMU8, Q6VRU3, Q6VRU4, Q9UHK6
isoenzyme IIB, calculated
31650
-
B3KMU8, Q6VRU3, Q6VRU4, Q9UHK6
isoenzyme IIA, calculated
38970
-
-
calculated for recombinant enzyme without six-His tag
39000
-
-
SDS-PAGE
40850
-
-
calculated for recombinant enzyme with six-His tag
42390
-
B3KMU8, Q6VRU3, Q6VRU4, Q9UHK6
isoenzyme IA, calculated
43830
-
Q3KT79
calculated from amino acid sequence
44700
-
-
gel filtration
45000
-
-
determined by SDS-PAGE
47150
-
-
calculated fpor His-tagged protein
47700
-
-
gel filtration
75000
-
-
dynamic light-scattering measurement
89000
-
-
gel filtration
SUBUNITS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
dimer
-
2 * 39000, SDS-PAGE
monomer
-
1 * 44900, SDS-PAGE
monomer
-
1 * 47100, SDS-PAGE
monomer
-
-
additional information
O06543
structure of the enzyme in complex with acetyl-CoA, acetoacetyl-CoA, (R,S)-ibuprofenoyl-CoA, (2S)-methylmyristoyl-CoA, or (2R)-methylmyristoyl-CoA, overview
Crystallization/COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
crystal structure at 1.8 A resolution
-
hanging-drop vapour-diffusion method, the best crystals grow in 1.26 M ammonium phosphate, pH 7.0 using a protein concentration of 24 mg/ml
-
purified recombinant wild-type enzyme in complex with acetyl-CoA, acetoacetyl-CoA, (R,S)-ibuprofenoyl-CoA, (2S)-methylmyristoyl-CoA, or (2R)-methylmyristoyl-CoA, 22C, hanging-drop vapor-diffusion method, with reservoir solution containing 1.52 M ammonium phosphate, 10 mM BaCl2 at pH 7.0 in 0.0066 ml drops containing a 1:1 v/v mixture of reservoir and protein solution, the latter containing 6 mg/ml in 10 mM potassium phosphate buffer, pH 8.8, X-ray diffraction structure determination and analysis at 1.6-2.3 A resolution
O06543
TEMPERATURE STABILITY
TEMPERATURE STABILITY MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
35
40
-
slow loss of activity
50
-
-
half-life: 15 min
Purification/COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
purification by affinity chromatography
-
by using metal ion affinity chromatography
-
Cloned/COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
AMACR 1A, the major splice variant, is expressed as a His-tag protein in Escherichia coli cells
-
expression in COS-7 cells
Q3KT79
expression in Escherichia coli; expression in Escherichia coli; expression in Escherichia coli; expression in Escherichia coli
B3KMU8, Q6VRU3, Q6VRU4, Q9UHK6
genotyping, determination of five non-synonymous and two intronic AMACR polymorphisms, no associations between the genetic variants and prostate cancer, overview
-
genotyping, determination of five single nucleotide polymorphisms tagging common haplotype variation within the coding and regulatory regions of AMACR, the risk of familial, but not sporadic, prostate cancer may be associated with germline variation in the AMACR gene, overview
-
-
O09174
expression in Escherichia coli
-
expression in Escherichia coli
-
overexpression in Escherichia coli
O06543
the open reading frame encoding alpha-methylacyl-coenzyme A racemase from Mycobacterium tuberculosis is subcloned into a pET15b vector, and the enzyme is overexpressed in Escherichia coli cells
-
expression in Escherichia coli
P70473
EXPRESSION
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
AMACR is negative in postatrophic hyperplasia, mucinous metaplasia, and urothelial metaplasia
-
partial atrophy shows negative and weak expression of alpha-methylacyl coenzyme A racemase in 75.3% and 24.7% acini, the secretory compartment in all variants of complete atrophy shows alpha-methylacyl coenzyme A racemase negative expression
-
patients with benign prostate hyperplasia have negative expression of AMACR
-
decreasing alpha-methylacyl-CoA racemase expression in tumors with less sebaceous differentiation, these findings provide insight into the potential pathogenesis of sebaceous neoplasms while assisting in the microscopic distinction of sebaceous adenoma from sebaceous carcinoma
-
coexpression of alpha-methylacyl coenzyme A racemase and nuclear p53 in neoplastic lesions
-
AMACR is overexpressed in prostate cancer
-
in addition to the over-expression in prostate carcinoma, enzyme is also over-expressed in a number of adenocarcinomas, notably colorectal carcinoma as well as in hepatocellular and renal cell carcinoma
-
positive AMACR immunehistochemistry staining is strongly associated with neoplastic transformation of the colon epithelium, AMACR positively is observed in the majority of invasive cancers and histologically recognized dysplasias
-
the expression of alpha-methylacyl-CoA racemase is increased in benign sebaceous glands and sebaceous hyperplasia
-
enzyme is strongly expressed in prostate cancer cell lines and tissues as compared with benign or normal prostate tissues, furthermore, enzyme is expressed abundantly in colorectal cancer, lung cancer tissues, renal and hepatic cancer, whereas it is barely detected in benign tissues and normal prostate epithelial cells
-
enzyme is over-expressed in prostate and other cancers
-
transcript levels of most AMACR splice variants are significantly upregulated in prostate cancer compared with its adjacent normal counterparts (in the order: IA>> IAd = IIA>> IIAs> IAs), while splice variant IB is the most abundant form of B variant and expression of splice variant IIB is negligible
-
ENGINEERING
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
C297A
-
mutant with 6.2% relative enzyme activity
D127A
-
mutant with 21.6% relative enzyme activity
D156A
-
mutant with 17.6% relative enzyme activity
D185A
-
mutant with 68.5% relative enzyme activity
D190A
-
mutant with 3.3% relative enzyme activity
D231A
-
mutant with 25.0% relative enzyme activity
D28A
-
mutant with 24.2% relative enzyme activity
D60A
-
mutant with 22.7% relative enzyme activity
D78A
-
mutant with 44.0% relative enzyme activity
E241A
-
mutant with 2.1% relative enzyme activity
E306A
-
mutant with 23.1% relative enzyme activity
E82A
-
mutant with 12.5% relative enzyme activity
E90A
-
mutant with 67.0% relative enzyme activity
E97A
-
mutant with 95.4% relative enzyme activity
H126A
-
mutant with 4.5% relative enzyme activity
H312A
-
mutant with 10.1% relative enzyme activity
I56P
-
mutant with 28.8% relative enzyme activity
K62A
-
mutant with 117.6% relative enzyme activity
M111P
-
mutant with 5.2% relative enzyme activity
R175A
-
mutant with 63.6% relative enzyme activity
R38A
-
mutant with 20.9% relative enzyme activity
R52A
-
mutant with 15.7% relative enzyme activity
R54A
-
mutant with 37.4% relative enzyme activity
R85A
-
mutant with 20.3% relative enzyme activity
R91A
-
mutant with 19.9% relative enzyme activity, 9fold increase of Km compared with the wild type
Y130A
-
mutant with 24.7% relative enzyme activity
Y224A
-
mutant with 22.6% relative enzyme activity
Y227A
-
mutant with 20.1% relative enzyme activity
APPLICATION
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
diagnostics
-
the enzyme is a tool in the diagnosis of morphologically difficult prostatic carcinoma and is used in combination with the basal cell markers p63 and 34betaE12, the enzyme might also be useful in diagnostics of extramammary Paget disease, EMPD
diagnostics
-
the enzyme is useful for detection of malignancies including hepatocellular carcinoma
diagnostics
-
the enzyme is a marker for prostate and renal cancer
diagnostics
-
the enzyme is a biomarker overexpressed in prostate carcinomas and is associated with prostate cancer progression
diagnostics
-
the enzyme can be used as a marker in the differential diagnosis of metanephric adenoma and as a molecular marker for prostate carcinoma
diagnostics
-
the enzyme is a sensitive and specific biomarker for the diagnosis of prostate cancer
diagnostics
-
cytokeratin 5/6 and AMACR applied as double sequential immunostains for diagnostic assessment of problematic prostate specimens
diagnostics
-
the elevated expression of the P504S gene and its enzyme product can serve as a molecular marker for prostate cancer
diagnostics
-
combined AMACR/p53 analysis to identify dysplasia in inflammatory bowel disease like ulcerative colitis and Crohns disease
diagnostics
-
AMACR is established as a valuable diagnostic marker for prostate cancer and has shown to be useful in the diagnosis of colorectal carcinoma
diagnostics
-
biomarker for cancer in prostate, breast, colon, renal and other cancer cells
drug development
-
AMACR can be an attractive target for cytotoxic T-lymphocyte-based immunotherapy for cancer
medicine
-
the activity of EC 5.1.99.4 may prove to be a valuable parameter for the prenatal diagnosis of general defects of peroxisome biogenesis such as Zellweger syndrome
medicine
-
the enzyme potentially can be used as an intermediate endpoint in chemoprevention trials or as a risk stratification tool among patients with negative prostatic biopsies. increased enzyme expression might be a characteristic of high-risk normal tissue
medicine
-
prognostic indicator in upper urinary tract urothelial cancer
medicine
-
in patients with gastric intestinal-type adenocarcinoma and its precursors, staining for alpha-methylacyl-CoA racemase is uniformly negative in samples negative for dysplasia and indefinite for dysplasia. In the groups of high-grade dysplasia and invasive intestinal-type adenocarcinoma, 76% and 34% of samples are positive for alpha-methylacyl-CoA racemase, respectively. Expression of alpha-methylacyl-CoA racemase is not correlated with location, Helicobacter pylori infection, or intestinal metaplasia
medicine
-
in patients with early Barrett's adenocarcinoma treated with surgery, 91% of cases with low-grade dysplasia show immunoreactivity for alpha-methylacyl-CoA racemase, and 96% of case with high-grade dysplasia and early Barrett's adenocarcinoma are positive for alpha-methylacyl-CoA racemase
medicine
-
in patients with noninvasive bladder cancer, there is a significant positive correlation between alpha-methylacyl-CoA racemase expression and higher tumor grades according to both the the 1973 World Health Organization and the 1998 WHO/International Society of Urological Pathology system
medicine
-
reduction of AMACR activity is proposed as a treatment for prostate and other cancers
medicine
-
AMACR is used as a diagnostic biomarker for prostate cancer and is a standard biomarker for needle biopsy specimens with ambiguous lesions
medicine
-
AMACR is a prognostic factor in prostate and colorectal cancer, AMACR expression is significantly associated with poor overall survival
medicine
-
alpha-methylacyl-coenzyme A racemase is a biomarker for prostate cancer and a putative target for the development of therapeutic agents directed against the disease, inhibition of enzyme activity may also act synergistically with androgen ablation therapy
pharmacology
-
the enzyme is partially validated as a potential therapeutic target by siRNA knockdown of the AMACR gene, overview