Information on EC 2.1.1.41 - sterol 24-C-methyltransferase

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

EC NUMBER
COMMENTARY
2.1.1.41
-
RECOMMENDED NAME
GeneOntology No.
sterol 24-C-methyltransferase
REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
S-adenosyl-L-methionine + 5alpha-cholesta-8,24-dien-3beta-ol = S-adenosyl-L-homocysteine + 24-methylene-5alpha-cholest-8-en-3beta-ol
show the reaction diagram
kinetic and inhibition mechanism; mechanism; steric substrate preferences: 3beta-hydroxy group, planar nucleus, side chain orientated into right-handed structure; structure-function relationship
-
S-adenosyl-L-methionine + 5alpha-cholesta-8,24-dien-3beta-ol = S-adenosyl-L-homocysteine + 24-methylene-5alpha-cholest-8-en-3beta-ol
show the reaction diagram
mechanism
-
S-adenosyl-L-methionine + 5alpha-cholesta-8,24-dien-3beta-ol = S-adenosyl-L-homocysteine + 24-methylene-5alpha-cholest-8-en-3beta-ol
show the reaction diagram
mechanism
-
S-adenosyl-L-methionine + 5alpha-cholesta-8,24-dien-3beta-ol = S-adenosyl-L-homocysteine + 24-methylene-5alpha-cholest-8-en-3beta-ol
show the reaction diagram
active site model, termed steric-electric plug model, consists of a non-covalent mechanism involving the intermediacy of a 24beta-methyl (or ethyl) sterol bound to the ternary complex; mechanism; substrate binding, amino acid sequence
-
S-adenosyl-L-methionine + 5alpha-cholesta-8,24-dien-3beta-ol = S-adenosyl-L-homocysteine + 24-methylene-5alpha-cholest-8-en-3beta-ol
show the reaction diagram
mechanism; substrate binding, amino acid sequence
-
S-adenosyl-L-methionine + 5alpha-cholesta-8,24-dien-3beta-ol = S-adenosyl-L-homocysteine + 24-methylene-5alpha-cholest-8-en-3beta-ol
show the reaction diagram
substrate binding, amino acid sequence
-
S-adenosyl-L-methionine + 5alpha-cholesta-8,24-dien-3beta-ol = S-adenosyl-L-homocysteine + 24-methylene-5alpha-cholest-8-en-3beta-ol
show the reaction diagram
kinetic and inhibition mechanism; mechanism
-
S-adenosyl-L-methionine + 5alpha-cholesta-8,24-dien-3beta-ol = S-adenosyl-L-homocysteine + 24-methylene-5alpha-cholest-8-en-3beta-ol
show the reaction diagram
substrate analogue inhibitor binding site structure
-
S-adenosyl-L-methionine + 5alpha-cholesta-8,24-dien-3beta-ol = S-adenosyl-L-homocysteine + 24-methylene-5alpha-cholest-8-en-3beta-ol
show the reaction diagram
-
-
-
-
REACTION TYPE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
methyl group transfer
-
-
-
-
PATHWAY
KEGG Link
MetaCyc Link
7-dehydroporiferasterol biosynthesis
-
Biosynthesis of secondary metabolites
-
ergosterol biosynthesis I
-
Metabolic pathways
-
plant sterol biosynthesis
-
Steroid biosynthesis
-
SYSTEMATIC NAME
IUBMB Comments
S-adenosyl-L-methionine:zymosterol 24-C-methyltransferase
Requires glutathione. Acts on a range of sterols with a 24(25)-double bond in the sidechain. While zymosterol is the preferred substrate it also acts on desmosterol, 5alpha-cholesta-7,24-dien-3beta-ol, 5alpha-cholesta-5,7,24-trien-3beta-ol, 4alpha-methylzymosterol and others. S-Adenosyl-L-methionine attacks the Si-face of the 24(25) double bond and the C-24 hydrogen is transferred to C-25 on the Re face of the double bond.
SYNONYMS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
(S)-adenosyl-L-methionine:DELTA24(25)-sterol methyl transferase
-
-
24-C-sterol methyltransferase
-
-
24-SMT
Cryptococcus neoformans 76484
-
-
-
24-SMT
Paracoccidioides brasiliensis Pb0, ATCC MYA-826
-
-
-
24-SMT
Trypanosoma brucei subsp. brucei
Q45KX5
-
24-SMT
Trypanosoma brucei subsp. brucei 427
Q45KX5
-
-
24-SMT
Trypanosoma brucei subsp. rhodesiense
-
-
24-SMT
Trypanosoma brucei subsp. rhodesiense STIB900
-
-
-
24-sterol C-methyltransferase
-
-
-
-
C-24 sterol methyltransferase
-
-
C24-methyltransferase
-
-
C24-sterol methyltransferase type 1
-
-
DELTA(24,25)-SMT
-
-
DELTA24-methyltransferase
-
-
-
-
DELTA24-sterol methyltransferase
-
-
-
-
DELTA24-sterol methyltransferase
-
-
DELTA24-sterol methyltransferase
Trypanosoma brucei subsp. brucei
Q45KX5
-
DELTA24-sterol methyltransferase
Trypanosoma brucei subsp. brucei 427
Q45KX5
-
-
DELTA24-sterol methyltransferase
Trypanosoma brucei subsp. rhodesiense
-
-
DELTA24-sterol methyltransferase
Trypanosoma brucei subsp. rhodesiense STIB900
-
-
-
DELTA24-sterol methyltransferase
-
-
GhSMT2-1
-
-
GhSMT2-2
-
-
methyltransferase, DELTA24-sterol
-
-
-
-
phytosterol methyltransferase
-
-
-
-
S-adenosyl-4-methionine:sterol DELTA24-methyltransferase
-
-
-
-
S-adenosyl-L-methionine:DELTA24(23)-sterol methyltransferase
-
-
-
-
SMT protein
A4IDL2
-
SMT protein
P25087
-
SMT1
-
-
-
-
SMT1
Gibberella sp., Glycine max
-
-
SMT1
Q43445
-
SMT2-1
-
-
sterol 24-C-methyltransferase
-
-
sterol 24-C-methyltransferase
A4IDL2
-
sterol 24C-methyltransferases
Q43445
-
sterol C24-methyltransferase
-
-
sterol C24-methyltransferases
-
-
sterol C24-methyltransferases
-
-
sterol C24-methyltransferases
-
-
sterol C24-methyltransferases
-
-
sterol C24-methyltransferases
Paracoccidioides brasiliensis Pb0, ATCC MYA-826
-
-
-
sterol C24-methyltransferases
-
-
sterol methyltransferase
Candida albicans, Gibberella sp.
-
-
sterol methyltransferase
-
-
sterol methyltransferase
-
-
sterol methyltransferase
-
-
zymosterol 24-methyltransferase
-
-
zymosterol-24(25)-methyltransferase
Q43445
-
zymosterol-24-methyltransferase
-
-
-
-
CAS REGISTRY NUMBER
COMMENTARY
37257-07-1
-
ORGANISM
COMMENTARY
LITERATURE
SEQUENCE CODE
SEQUENCE DB
SOURCE
3 isozymes encoded on SMT1, SMT2, SMT3
-
-
Manually annotated by BRENDA team
3 isozymes encoded on SMT1, SMT2, SMT3
Uniprot
Manually annotated by BRENDA team
strain 76484
-
-
Manually annotated by BRENDA team
Cryptococcus neoformans 76484
strain 76484
-
-
Manually annotated by BRENDA team
Gibberella sp.
-
-
-
Manually annotated by BRENDA team
gene SMT1
-
-
Manually annotated by BRENDA team
sunflower
-
-
Manually annotated by BRENDA team
cloning of SMT protein of
SwissProt
Manually annotated by BRENDA team
mutant strain GL7
-
-
Manually annotated by BRENDA team
strain A184D erg+ and sterol mutant strain +erg2
-
-
Manually annotated by BRENDA team
Trypanosoma brucei subsp. brucei
strain 427
SwissProt
Manually annotated by BRENDA team
Trypanosoma brucei subsp. brucei 427
strain 427
SwissProt
Manually annotated by BRENDA team
Trypanosoma brucei subsp. rhodesiense
strain STIB900
-
-
Manually annotated by BRENDA team
Trypanosoma brucei subsp. rhodesiense STIB900
strain STIB900
-
-
Manually annotated by BRENDA team
corn
-
-
Manually annotated by BRENDA team
GENERAL INFORMATION
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
malfunction
-
the SMT2 genes of soybean (SMT2-1 and SMT2-2) are shown to complement the SMT deficient cvp1 mutant Arabidopsis plants
malfunction
-
transgenic Arabidopsis seeds expressing GmSMT1 or GmSMT2 show modifications in the ratio of 24-methyl to 24-ethyl sterol in the direction of sitosterol formation
malfunction
-
Deficiency of SMT2 in the cvp1 mutant results in moderate developmental defects, including aberrant cotyledon vein patterning, serrated floral organs, and reduced stature, but plants are viable, suggesting that SMT3 activity can substitute for the loss of SMT2. The overexpression of SMT3 complements the cotyledon venation pattern defects of cvp1 (SMT2) mutants; smt3 single mutants appear wild type, cvp1 smt3 double mutants show enhanced defects relative to cvp1 mutants, such as discontinuous cotyledon vein pattern, and produce novel phenotypes, including defective root growth, loss of apical dominance, sterility, and homeotic floral transformations. Antisense smt3 plants did not display a phenotype, suggesting that SMT3 and SMT2 are functionally redundant
metabolism
-
key enzyme in the biosynthesis of ergosterol
SUBSTRATE
PRODUCT                      
REACTION DIAGRAM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
(Substrate)
LITERATURE
(Substrate)
COMMENTARY
(Product)
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
(3beta)-3-fluorolanost-8,24-diene + S-adenosyl-L-methionine
(3beta)-3-fluoro-24-methylidenelanost-8-ene + S-adenosyl-L-homocysteine
show the reaction diagram
-
catalytic competence: 16%
-
-
?
(3beta)-3-methoxylanosta-8,24-diene + S-adenosyl-L-methionine
(3beta)-3-methoxy-24-methylidenelanost-8-ene + S-adenosyl-L-homocysteine
show the reaction diagram
-
catalytic competence: 18%
-
-
?
(3beta)-lanosta-8,24-dien-3-amine + S-adenosyl-L-methionine
(3beta)-24-methylidenelanost-8-en-3-amine + S-adenosyl-L-homocysteine
show the reaction diagram
-
catalytic competence: 22%
-
-
?
(3beta)-lanosta-8,24-dien-3-yl acetate + S-adenosyl-L-methionine
(3beta)-24-methylidenelanost-8-en-3-yl acetate + S-adenosyl-L-homocysteine
show the reaction diagram
-
catalytic competence: 29%
-
-
?
14alpha-methylergosta-8,24(28)-diene + S-adenosyl-L-methionine
?
show the reaction diagram
-
-
-
-
?
14alpha-methylzymosterol + S-adenosyl-L-methionine
14alpha-methyl-24-methylenezymosterol + S-adenosyl-L-homocysteine
show the reaction diagram
-
14alpha-methylzymosterol is 14alpha-methylcholesta-8,24-dien-3beta-ol
-
-
?
14alpha-methylzymosterol + S-adenosyl-L-methionine
14alpha-methyl-24-methylenezymosterol + S-adenosyl-L-homocysteine
show the reaction diagram
Cryptococcus neoformans, Cryptococcus neoformans 76484
-
37% activity compared to lanosterol
-
-
?
24(28)-methylene lophenol + S-adenosyl-L-methionine
?
show the reaction diagram
-
-
-
-
?
24,25-dehydropollinastanol + S-adenosyl-L-methionine
?
show the reaction diagram
-
24,25-dehydropollinastanol is 14alpha-methyl-9beta,19-cyclo-5alpha-cholest-24-en-3beta-ol
-
-
?
24-methylenecholesterol + S-adenosyl-L-methionine
24-ethylidenecholesterol + S-adenosyl-L-homocysteine
show the reaction diagram
-
5% the reaction rate of zymosterol
-
?
24-methylenelanosterol + S-adenosyl-L-methionine
pneumocysterol + S-adenosyl-L-homocysteine
show the reaction diagram
-
preferred substrate
-
?
26,27-dehydrozymosterol + S-adenosyl-L-methionine
26-homo-cholesta-8(9),23(24)E,26(26')-trienol + 26-homo-cholesta-8(9),26(26')-3beta,24beta-dienol + S-adenosyl-L-homocysteine
show the reaction diagram
-
mutants
-
?
26,27-dehydrozymosterol + S-adenosyl-L-methionine
? + S-adenosyl-L-homocysteine
show the reaction diagram
-
in contrast to the results with zymosterol, product analysis of the 26,27-dehydrozymosterol assays shows that multiple products are produced that occurred in different ratios determined by HPLC-radiocounting of the non-saponifiable lipid fractions. In these analyses two major product classes are identified, a neutral C26 sterol monol and a pair of C26-oxygenated diols
-
-
?
31-norcycloartenol + S-adenosyl-L-methionine
24-methylene-31-norcycloartenol + S-adenosyl-L-homocysteine
show the reaction diagram
-
31-norcycloartenol is 4,14alpha-dimethyl-9beta,19-cyclo-5alpha-cholest-24-en-3beta-ol
-
-
?
31-norlanosterol + S-adenosyl-L-methionine
?
show the reaction diagram
Cryptococcus neoformans, Cryptococcus neoformans 76484
-
78% activity compared to lanosterol
-
-
?
4alpha-methylzymosterol + S-adenosyl-L-methionine
?
show the reaction diagram
Cryptococcus neoformans, Cryptococcus neoformans 76484
-
43% activity compared to lanosterol
-
-
?
5-dehydroepisterol + S-adenosyl-L-methionine
?
show the reaction diagram
-
-
-
-
?
agnosterol + S-adenosyl-L-methionine
24-methyleneagnosterol + S-adenosyl-L-homocysteine
show the reaction diagram
-
agnosterol is 4,4,14alpha-trimethyl-5alpha-cholesta-7(8),9(11),24-trien-3beta-ol
-
-
?
cholesta-5,7,24-triene + S-adenosyl-L-methionine
?
show the reaction diagram
-
-
-
-
?
cholesta-5,7,24-trienol + S-adenosyl-L-methionine
?
show the reaction diagram
-
-
-
-
?
cholesta-7,24-diene + S-adenosyl-L-methionine
?
show the reaction diagram
-
-
-
-
?
cholesterol + S-adenosyl-L-methionine
?
show the reaction diagram
-
-
-
-
?
cycloartenol + S-adenosyl-L-methionine
24-methylenecycloartenol + S-adenosyl-L-homocysteine
show the reaction diagram
-
-
-
-
?
cycloartenol + S-adenosyl-L-methionine
24-methylenecycloartenol + S-adenosyl-L-homocysteine
show the reaction diagram
-
-
-
?
cycloartenol + S-adenosyl-L-methionine
24-methylenecycloartenol + S-adenosyl-L-homocysteine
show the reaction diagram
-, Q43445
-
-
?
cycloartenol + S-adenosyl-L-methionine
24-methylenecycloartenol + S-adenosyl-L-homocysteine
show the reaction diagram
-
-
-
-
?
cycloartenol + S-adenosyl-L-methionine
24-methylenecycloartenol + S-adenosyl-L-homocysteine
show the reaction diagram
-
-
-
?
cycloartenol + S-adenosyl-L-methionine
24-methylenecycloartenol + S-adenosyl-L-homocysteine
show the reaction diagram
-
-
-
-
?
cycloartenol + S-adenosyl-L-methionine
24-methylenecycloartenol + S-adenosyl-L-homocysteine
show the reaction diagram
-
-
-
?
cycloartenol + S-adenosyl-L-methionine
24-methylenecycloartenol + S-adenosyl-L-homocysteine
show the reaction diagram
-
no substrate
-
-
-
cycloartenol + S-adenosyl-L-methionine
24-methylenecycloartenol + S-adenosyl-L-homocysteine
show the reaction diagram
-
cycloartenol is 4,4,14alpha-trimethyl-9beta,19-cyclo-5alpha-cholest-24-en-3beta-ol
-
-
?
cycloartenol + S-adenosyl-L-methionine
24-methylenecycloartenol + S-adenosyl-L-homocysteine
show the reaction diagram
-
cycloartenol is 4,4,14alpha-trimethyl-9beta,19-cyclo-5alpha-cholest-24-en-3beta-ol
-
?
cycloartenol + S-adenosyl-L-methionine
24-methylenecycloartenol + S-adenosyl-L-homocysteine
show the reaction diagram
-, Q43445
rate-limiting initial step in the conversion of phytosterol
-
-
-
cycloartenol + S-adenosyl-L-methionine
24-methylenecycloartanol + S-adenosyl-L-homocysteine
show the reaction diagram
-
-
-
-
?
cycloartenol + S-adenosyl-L-methionine
24(28)-methylene cycloartanol + S-adenosyl-L-homocysteine
show the reaction diagram
-
optimal substrate for SMT1
-
-
?
cycloartenol 3-ketone + S-adenosyl-L-methionine
?
show the reaction diagram
-
cycloartenol 3-ketone is 4,4,14alpha-trimethyl-9beta,19-cyclo-5alpha-cholest-24-en-3-one
-
-
?
dehydroergosterol + S-adenosyl-L-methionine
?
show the reaction diagram
-
-
-
-
?
desmosterol + S-adenosyl-L-methionine
24-methylenedesmosterol + S-adenosyl-L-homocysteine
show the reaction diagram
-
-
-
-
-
desmosterol + S-adenosyl-L-methionine
24-methylenedesmosterol + S-adenosyl-L-homocysteine
show the reaction diagram
-
-
-
-
?
desmosterol + S-adenosyl-L-methionine
24-methylenedesmosterol + S-adenosyl-L-homocysteine
show the reaction diagram
Trypanosoma brucei subsp. brucei
Q45KX5
-
-
-
?
desmosterol + S-adenosyl-L-methionine
24-methylenedesmosterol + S-adenosyl-L-homocysteine
show the reaction diagram
Trypanosoma brucei subsp. rhodesiense
-
-
-
-
?
desmosterol + S-adenosyl-L-methionine
24-methylenedesmosterol + S-adenosyl-L-homocysteine
show the reaction diagram
-
desmosterol is 5alpha-cholesta-5,24-dien-3beta-ol
-
-
?
desmosterol + S-adenosyl-L-methionine
24-methylenedesmosterol + S-adenosyl-L-homocysteine
show the reaction diagram
-
desmosterol is 5alpha-cholesta-5,24-dien-3beta-ol
-
-
?
desmosterol + S-adenosyl-L-methionine
24-methylenedesmosterol + S-adenosyl-L-homocysteine
show the reaction diagram
-
desmosterol is 5alpha-cholesta-5,24-dien-3beta-ol
-
?
desmosterol + S-adenosyl-L-methionine
24-methylenedesmosterol + S-adenosyl-L-homocysteine
show the reaction diagram
Trypanosoma brucei subsp. rhodesiense STIB900
-
-
-
-
?
desmosterol + S-adenosyl-L-methionine
24-methylenedesmosterol + S-adenosyl-L-homocysteine
show the reaction diagram
Trypanosoma brucei subsp. brucei 427
Q45KX5
-
-
-
?
ergosta-5,8,22,24(28)-tetraene + S-adenosyl-L-methionine
?
show the reaction diagram
-
-
-
-
?
ergosterol + S-adenosyl-L-methionine
?
show the reaction diagram
-
-
-
-
?
lanost-24-enol + S-adenosyl-L-methionine
24-methylene-lanost-24-erol + S-adenosyl-L-homocysteine
show the reaction diagram
-
lanost-24-enol is 4,4,14alpha-trimethyl-5alpha-cholesta-9(11),24-dien-3beta-ol
-
-
?
lanosta-7,24-dienol + S-adenosyl-L-methionine
24-methylene-lanost-7,24-dienol + S-adenosyl-L-homocysteine
show the reaction diagram
-
lanosta-7,24-dienol is 4,4,14alpha-trimethyl-5alpha-cholesta-7(8),24-dien-3beta-ol
-
-
?
lanosta-8,24-dien-3-one + S-adenosyl-L-methionine
24-methylidenelanost-8-en-3-one + S-adenosyl-L-homocysteine
show the reaction diagram
-
catalytic competence: 48%
-
-
?
lanosterol + S-adenosyl-L-methionine
24-methylene-24,25-dihydrolanosterol + S-adenosyl-L-homocysteine
show the reaction diagram
-
-
-
?
lanosterol + S-adenosyl-L-methionine
24-methylene-24,25-dihydrolanosterol + S-adenosyl-L-homocysteine
show the reaction diagram
-
-
-
-
?
lanosterol + S-adenosyl-L-methionine
24-methylene-24,25-dihydrolanosterol + S-adenosyl-L-homocysteine
show the reaction diagram
-
-
-
?
lanosterol + S-adenosyl-L-methionine
24-methylene-24,25-dihydrolanosterol + S-adenosyl-L-homocysteine
show the reaction diagram
Gibberella sp.
-
-
-
-
?
lanosterol + S-adenosyl-L-methionine
24-methylene-24,25-dihydrolanosterol + S-adenosyl-L-homocysteine
show the reaction diagram
-
-
-
?
lanosterol + S-adenosyl-L-methionine
24-methylene-24,25-dihydrolanosterol + S-adenosyl-L-homocysteine
show the reaction diagram
-
-
-
-
?
lanosterol + S-adenosyl-L-methionine
24-methylene-24,25-dihydrolanosterol + S-adenosyl-L-homocysteine
show the reaction diagram
-
preferred substrate
-
?
lanosterol + S-adenosyl-L-methionine
24-methylene-24,25-dihydrolanosterol + S-adenosyl-L-homocysteine
show the reaction diagram
-
no reaction with
-
-
-
lanosterol + S-adenosyl-L-methionine
24-methylene-24,25-dihydrolanosterol + S-adenosyl-L-homocysteine
show the reaction diagram
-
lanosterol is 4,4,14alpha-trimethyl-5alpha-cholesta-8,24-dien-3-ol
-
?
lanosterol + S-adenosyl-L-methionine
24-methylene-24,25-dihydrolanosterol + S-adenosyl-L-homocysteine
show the reaction diagram
-
lanosterol is 4,4,14alpha-trimethyl-5alpha-cholesta-8,24-dien-3-ol
-
-
?
lanosterol + S-adenosyl-L-methionine
24-methylene-24,25-dihydrolanosterol + S-adenosyl-L-homocysteine
show the reaction diagram
-
regiospecific
-
-
?
lanosterol + S-adenosyl-L-methionine
24-methylene-24,25-dihydrolanosterol + S-adenosyl-L-homocysteine
show the reaction diagram
Cryptococcus neoformans, Cryptococcus neoformans 76484
-
100% activity, lanosterol is the optimal acceptor molecule
-
-
?
S-adenosyl-L-methionine + 26,27-dehydrolanosterol
?
show the reaction diagram
-
-
-
-
?
S-adenosyl-L-methionine + 31-norlanosterol
?
show the reaction diagram
-
-
-
-
?
S-adenosyl-L-methionine + 5alpha-cholesta-8,24-dien-3beta-ol
S-adenosyl-L-homocysteine + 24-methylene-5alpha-cholest-8-en-3beta-ol
show the reaction diagram
-
3-hydroxy-3-methylglutaryl CoA reductase and C24-sterol methyltransferase type 1 work in concert to control carbon flux into end-product sterols. Sterol composition can be controlled by the temporal activity of the promoters driving transgene expression
-
-
?
S-adenosyl-L-methionine + cycloartenol
S-adenosyl-L-homocysteine + 24-methylenecycloartenol
show the reaction diagram
-
-
-
-
?
S-adenosyl-L-methionine + lanosterol
S-adenosyl-L-homocysteine + 24-methylene-24,25-dihydrolanosterol
show the reaction diagram
-
-
-
-
?
S-adenosyl-L-methionine + zymosterol
S-adenosyl-L-homocysteine + fecosterol
show the reaction diagram
P25087
-
-
-
?
S-adenosyl-L-methionine + zymosterol
S-adenosyl-L-homocysteine + fecosterol
show the reaction diagram
-
-
-
-
?
S-adenosyl-L-methionine + zymosterol
S-adenosyl-L-homocysteine + fecosterol
show the reaction diagram
-
-
-
-
?
S-adenosyl-L-methionine + zymosterol
S-adenosyl-L-homocysteine + fecosterol
show the reaction diagram
-
-
-
-
?
S-adenosyl-L-methionine + zymosterol
S-adenosyl-L-homocysteine + fecosterol
show the reaction diagram
-
the active center is composed of a set of acidic amino acids, Asp125, Asp152, Glu195 and Asp276, which contribute to initial binding of sterol and S-adenosyl-L-methionine. His90 functions subsequently in the reaction process to promote product formation
-
-
?
S-adenosyl-L-methionine + zymosterol
?
show the reaction diagram
-
GC-MS analysis of the enzyme-generated products from a soluble TbSMT shows the presence of four biomethylated sterols identified as ergosta-8,25(27)-dienol, ergosta-8,24(28)-dienol, ergosta-8,24(25)-dienol and 24-dimethyl ergosta-8,25(27)-dienol in a ratio of substrate/product of 7:3. The products distributed in a ratio of approximately 5:1:2:2 respectively
-
-
?
zymosterol + S-adenosyl-L-methionine
fecosterol + S-adenosyl-L-homocysteine
show the reaction diagram
-
-
-
-
?
zymosterol + S-adenosyl-L-methionine
fecosterol + S-adenosyl-L-homocysteine
show the reaction diagram
-
-
-
-
?
zymosterol + S-adenosyl-L-methionine
fecosterol + S-adenosyl-L-homocysteine
show the reaction diagram
-
-
-
-
?
zymosterol + S-adenosyl-L-methionine
fecosterol + S-adenosyl-L-homocysteine
show the reaction diagram
Q43445
-
-
-
?
zymosterol + S-adenosyl-L-methionine
fecosterol + S-adenosyl-L-homocysteine
show the reaction diagram
-
-
-
-
?
zymosterol + S-adenosyl-L-methionine
fecosterol + S-adenosyl-L-homocysteine
show the reaction diagram
Q9LM02
-
-
-
?
zymosterol + S-adenosyl-L-methionine
fecosterol + S-adenosyl-L-homocysteine
show the reaction diagram
-
-
-
-
?
zymosterol + S-adenosyl-L-methionine
fecosterol + S-adenosyl-L-homocysteine
show the reaction diagram
-
-
-
-
?
zymosterol + S-adenosyl-L-methionine
fecosterol + S-adenosyl-L-homocysteine
show the reaction diagram
-
-
-
-
?
zymosterol + S-adenosyl-L-methionine
fecosterol + S-adenosyl-L-homocysteine
show the reaction diagram
-
-
-
-
?
zymosterol + S-adenosyl-L-methionine
fecosterol + S-adenosyl-L-homocysteine
show the reaction diagram
-
-
-
-
?
zymosterol + S-adenosyl-L-methionine
fecosterol + S-adenosyl-L-homocysteine
show the reaction diagram
-
-
-
-
?
zymosterol + S-adenosyl-L-methionine
fecosterol + S-adenosyl-L-homocysteine
show the reaction diagram
-
-
-
-
?
zymosterol + S-adenosyl-L-methionine
fecosterol + S-adenosyl-L-homocysteine
show the reaction diagram
-
-
-
-
?
zymosterol + S-adenosyl-L-methionine
fecosterol + S-adenosyl-L-homocysteine
show the reaction diagram
-
-
fecosterol is 24-exomethylene-5alpha-cholesta-8,24-dien-3beta-ol
?
zymosterol + S-adenosyl-L-methionine
fecosterol + S-adenosyl-L-homocysteine
show the reaction diagram
-
wild-type and mutants
-
-
?
zymosterol + S-adenosyl-L-methionine
fecosterol + S-adenosyl-L-homocysteine
show the reaction diagram
-
regio- and stereospecific for substrates
-
-
?
zymosterol + S-adenosyl-L-methionine
fecosterol + S-adenosyl-L-homocysteine
show the reaction diagram
-
regio- and stereospecific for substrates
-
?
zymosterol + S-adenosyl-L-methionine
fecosterol + S-adenosyl-L-homocysteine
show the reaction diagram
-
zymosterol is 5alpha-cholesta-8,24-dien-3beta-ol
-
-
?
zymosterol + S-adenosyl-L-methionine
fecosterol + S-adenosyl-L-homocysteine
show the reaction diagram
-
zymosterol is 5alpha-cholesta-8,24-dien-3beta-ol
-
-
?
zymosterol + S-adenosyl-L-methionine
fecosterol + S-adenosyl-L-homocysteine
show the reaction diagram
-
zymosterol is 5alpha-cholesta-8,24-dien-3beta-ol
-
-
?
zymosterol + S-adenosyl-L-methionine
fecosterol + S-adenosyl-L-homocysteine
show the reaction diagram
-
zymosterol is 5alpha-cholesta-8,24-dien-3beta-ol
-
-
?
zymosterol + S-adenosyl-L-methionine
fecosterol + S-adenosyl-L-homocysteine
show the reaction diagram
-
zymosterol is 5alpha-cholesta-8,24-dien-3beta-ol
fecosterol is 24-exomethylene-5alpha-cholesta-8,24-dien-3beta-ol
?
zymosterol + S-adenosyl-L-methionine
fecosterol + S-adenosyl-L-homocysteine
show the reaction diagram
-
role in biosynthesis of plant and fungi sterols
-
-
?
zymosterol + S-adenosyl-L-methionine
fecosterol + S-adenosyl-L-homocysteine
show the reaction diagram
-
the enzyme catalyzes an enzymatic step following C-4 demethylation of 4,4-dimethylzymosterol. Erg28p anchors the C-4 demethylation enzyme complex to the endoplasmic reticulum and acts as a protein bridge to the Erg6p enzyme required for the next ergisterol biosynthetic step
-
-
?
zymosterol + S-adenosyl-L-methionine
fecosterol + S-adenosyl-L-homocysteine
show the reaction diagram
-
a bisubstrate reaction that proceeds by a sequential and noncovalent reaction whereby beta-face methyl addition to the DELTA24-bond and deprotonation of C-28 proceed to give rise to a nucleophilic rearrangement in which H-24 migrates to C-25 on the reface of the substrate double bond in concert with the initial ionization to afford the bound fecosterol
-
-
?
zymosterol + S-adenosyl-L-methionine
fecosterol + S-adenosyl-L-homocysteine
show the reaction diagram
-
C4-demethyl sterols with double bonds in the nucleus at positions 8, 7, or 5 are acceptable substrates
-
-
?
zymosterol + S-adenosyl-L-methionine
24-methylzymosta-8,25(27)-dienol + S-adenosyl-L-homocysteine
show the reaction diagram
-
mutants D79L and E82L
-
?
zymosterol + S-adenosyl-L-methionine
?
show the reaction diagram
-
-
-
-
?
zymosterol + S-adenosyl-L-methionine
?
show the reaction diagram
-
61% activity compared to lanosterol
-
-
?
lanosterol-3beta-OH + S-adenosyl-L-methionine
24-methylene-24,25-dihydrolanosterol + S-adenosyl-L-homocysteine
show the reaction diagram
-
catalytic competence: 100%
-
-
?
additional information
?
-
-
overview about a large number of sterol substrates of various origin, substrate specificity analysis, structures: overview
-
-
-
additional information
?
-
-
minimum requirements for productive binding and formation of catalytically active enzyme-substrate complex must be a substrate that possesses a 3beta-hydroxy group, a planar nucleus, an intact side chain that retains the length of the native substrate zymosterol, a 20-R configuration and a delta24-double bond
-
-
-
additional information
?
-
-
neither lanosterol nor other C4-methyl-containing sterols bind productively to the enzyme
-
-
-
additional information
?
-
A4IDL2, -
enzyme involved in biosynthesis of ergosterol, which is a target molecule of leishmanicidal and fungicidal amphotericin B, used for vaccine development
-
-
-
additional information
?
-
P25087
formation of the ergostane (C1-transfer activity) and stigmastane (C2-transfer activity) sterol side chains, stepwise mutagenesis of amino acids of Erg6p, identification of five residues within the putative active site that contribute directly to C-methylation pathways operated by fungal and plant SMT proteins
-
-
-
additional information
?
-
Cryptococcus neoformans, Cryptococcus neoformans 76484
-
eburicol and obtusifoliol are no substrates
-
-
-
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
cycloartenol + S-adenosyl-L-methionine
24-methylenecycloartenol + S-adenosyl-L-homocysteine
show the reaction diagram
-, Q43445
-
-
?
cycloartenol + S-adenosyl-L-methionine
24-methylenecycloartenol + S-adenosyl-L-homocysteine
show the reaction diagram
-, Q43445
rate-limiting initial step in the conversion of phytosterol
-
-
-
S-adenosyl-L-methionine + 5alpha-cholesta-8,24-dien-3beta-ol
S-adenosyl-L-homocysteine + 24-methylene-5alpha-cholest-8-en-3beta-ol
show the reaction diagram
-
3-hydroxy-3-methylglutaryl CoA reductase and C24-sterol methyltransferase type 1 work in concert to control carbon flux into end-product sterols. Sterol composition can be controlled by the temporal activity of the promoters driving transgene expression
-
-
?
zymosterol + S-adenosyl-L-methionine
fecosterol + S-adenosyl-L-homocysteine
show the reaction diagram
-
-
-
-
?
zymosterol + S-adenosyl-L-methionine
fecosterol + S-adenosyl-L-homocysteine
show the reaction diagram
-
-
-
-
?
zymosterol + S-adenosyl-L-methionine
fecosterol + S-adenosyl-L-homocysteine
show the reaction diagram
-, Q43445
-
-
-
?
zymosterol + S-adenosyl-L-methionine
fecosterol + S-adenosyl-L-homocysteine
show the reaction diagram
-
-
-
-
?
zymosterol + S-adenosyl-L-methionine
fecosterol + S-adenosyl-L-homocysteine
show the reaction diagram
Q9LM02
-
-
-
?
zymosterol + S-adenosyl-L-methionine
fecosterol + S-adenosyl-L-homocysteine
show the reaction diagram
-
-
-
-
?
zymosterol + S-adenosyl-L-methionine
fecosterol + S-adenosyl-L-homocysteine
show the reaction diagram
-
-
-
-
?
zymosterol + S-adenosyl-L-methionine
fecosterol + S-adenosyl-L-homocysteine
show the reaction diagram
-
-
-
-
?
zymosterol + S-adenosyl-L-methionine
fecosterol + S-adenosyl-L-homocysteine
show the reaction diagram
-
-
-
-
?
zymosterol + S-adenosyl-L-methionine
fecosterol + S-adenosyl-L-homocysteine
show the reaction diagram
-
-
-
-
?
zymosterol + S-adenosyl-L-methionine
fecosterol + S-adenosyl-L-homocysteine
show the reaction diagram
-
-
-
-
?
zymosterol + S-adenosyl-L-methionine
fecosterol + S-adenosyl-L-homocysteine
show the reaction diagram
-
role in biosynthesis of plant and fungi sterols
-
-
?
zymosterol + S-adenosyl-L-methionine
fecosterol + S-adenosyl-L-homocysteine
show the reaction diagram
-
the enzyme catalyzes an enzymatic step following C-4 demethylation of 4,4-dimethylzymosterol. Erg28p anchors the C-4 demethylation enzyme complex to the endoplasmic reticulum and acts as a protein bridge to the Erg6p enzyme required for the next ergisterol biosynthetic step
-
-
?
COFACTOR
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
S-adenosyl-L-methionine
-
-
S-adenosyl-L-methionine
-
-
S-adenosyl-L-methionine
-
-
S-adenosyl-L-methionine
-
-
S-adenosyl-L-methionine
-
-
METALS and IONS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
Mg2+
-
5 mM, required
additional information
-
no metal ion required
INHIBITORS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
(24,S),25-epiminozymosterol
-
-
(24R)-24-methyl-25,26,27-trisnor-24-dimethylamino-N-oxide cycloartenol
-
-
(24R)-24-methyl-25-azacycloartenol
-
-
(24R)-methyl-25-thiacholesteryl iodide
-
-
(24R,S),25-epiminolanosterol
-
-
(24R,S),25-epiminolanosterol
-
-
(24R,S),25-epiminozymosterol
-
-
(24R,S)-24-Ethyl-25-azacycloartenol
-
-
(24R,S)-24-Methyl-25,26,27-trisnor-24-dimethylamino-N-oxide cycloartenol
-
-
(24R,S)-24-Methyl-25,26,27-trisnor-24-dimethylsulfonium cycloartenol iodide
-
-
(24R,S)-24-Methyl-25,26,27-trisnor-24-trimethylarsonium cycloartenol iodide
-
-
(24R,S)-24-Methyl-25-azacycloartenol
-
-
(24S)-24-methyl-25,26,27-trisnor-24-dimethylamino-N-oxide cycloartenol
-
-
(24S)-24-methyl-25-azacycloartenol
-
-
(24S)-methyl-25-thiacholesteryl iodide
-
-
(3beta,24,R,S)-24-methyl-24-thioniacholest-5-enol
-
-
(3S,20R)-20-(propylamino-ethyl)-pregn-7-en-3-ol
-
-
(3S,20S)-20-(butylamino-methyl)-pregn-7-en-3-ol
-
-
(3S,20S)-20-(ethylamino-methyl)-pregn-7-en-3-ol
-
-
(3S,20S)-20-(methylamino-methyl)-pregn-7-en-3-ol
-
-
(3S,20S)-20-(pentylamino-methyl)-pregn-7-en-3-ol
-
-
(3S,20S)-20-(propylamino-methyl)-pregn-7-en-3-ol
-
-
(3S,20S)-20-[(1R,S)-(1,2-dimethyl-propylamino)-methyl]-pregn-7-en-3-ol
-
-
(3S,20S)-20-[(2-dimethylamino-ethylamino)-methyl]-pregn-7-en-3-ol
-
-
(3S,20S)-20-[(2-methylpropyl)amino-methyl]-pregn-7-en-3-ol
-
-
(3S,20S)-20-[(2-pyrrolidin-1-yl-ethylamino)-methyl]-pregn-7-en-3-ol
-
-
(3S,20S)-20-[(3-dimethylamino-propylamino)-methyl]-pregn-7-en-3-ol
-
-
(R,S)-24,25-epiminolanosterol
-
-
(R,S)-S-butyl-S-[(3S,20S)-(3-hydroxypregn-7-en-20-yl)-methyl]-S-methyl-sulfonium iodide
-
-
2-(3S,20R)-[(E)-2-(3-hydroxypregn-7-en-20-yl)-ethenyl]-1-methylpyridinium iodide
-
-
22,25-Diazacholesterol
-
20R and 20S isomer
22,26-azasterol
Trypanosoma brucei subsp. brucei
Q45KX5
-
22,26-azasterol
Trypanosoma brucei subsp. rhodesiense
-
-
22,26-azasterol
-
-
22-piperidin-3-yl-pregnan-22(S),3beta-diol
-
-
23-Azacholesterol
-
-
23-Azacholesterol
-
-
23-Azacholesterol
-
-
24(28)-methylene cycloartanol
-
-
24(28)-methylenecycloartanol
-
noncompetitive with respect to S-adenosyl-L-methionine
24(28)-methylenecycloartenol
-
-
24(R,S),25-epiminolanosterol
-
-
24(R,S),25-epiminolanosterol
-
-
24(R,S),25-epiminozymosterol
-
reversible inhibitor, disrupts ergosterol homoeostasis by interrupting methyl addition to C-24 thereby impairing growth
24(R,S)-25-epiminolanosterol
-
-
24(S)-24-methyl-25-thiacholest-5-enol iodide
-
-
24-Azacholesterol
-
-
24-Azacholesterol
-
-
24-Azacycloartanyl acetate
-
-
24-Methyl-25,26,27-trisnor-24-trimethylammonium cycloartenol iodide
-
24R and 24S isomer
24-Methyl-25-azacycloartenol
-
24R and 24S isomer
24-Oxo-25-azacycloartenol
-
-
24-thialanosterol
-
-
-
24beta-aminolanosterol
-
-
25,26,27-Trisnor-24-trimethylammonium cycloartenol iodide
-
-
25-aminolanosterol
-
-
25-aza-24,25-dihydrolanosterol
-
-
25-Aza-24,25-dihydrozymosterol
-
-
25-Azacholestanol
-
-
25-Azacholesterol
-
-
25-Azacholesterol hydrochloride
-
-
25-Azacycloartenol
-
-
25-Azacycloartenol
-
noncompetitive versus cycloartenol and uncompetitive versus S-adenosyl-L-methionine
25-azacyloartenol
-
-
25-azalanosterol
-
-
-
25-azalanosterol
-
-
-
25-azalanosterol
-
-
-
25-azalanosterol
-
-
-
25-thiacholesterol iodide
-
-
25-thialanosterol iodide
-
-
26,27-dehydrolanosterol
-
-
-
26,27-dehydrozymosterol
-
mechanism-based irreversible inhibition
26,27-dehydrozymosterol
-
irreversible inhibitor that binds covalently to the SMT, affinitylabels the active site to convert to a product characterized as delta23(24)-sterol
26,27-dehydrozymosterol
-
-
26,27-dehydrozymosterol
-
-
26,27-dehydrozymosterol
-
-
26-nor-25-thialanosterol
-
-
3-aminolanosterol
-
-
30-amino-24,25-dihydrolanosterol
-
-
4-(3S,20R)-[(E)-2-(3-hydroxypregn-7-en-20-yl)-ethenyl]-1-methylpyridinium iodide
-
-
5'-deoxy-5'-(methylthio)adenosine
-
AdoMet analog, competitive inhibitor
7-amino-24,25-dihydrolanosterol
-
-
amphotericine B
-
inhibits the wild-type at concentrations above 60 nM, inhibition can be hindered by zymosterol
azasterol
Trypanosoma brucei subsp. brucei
Q45KX5
-
cholesta-8,24(28)-dienol
-
-
-
cyclolaudenol
-
dead-end inhibitor, competitive versus cycloartenol and uncompetitive versus S-adenosyl-L-methionine
desmosterol
-
competitive versus sterol and S-adenosyl-L-methionine
ergosta-5,7,22-trienol
-
-
-
ergosterol
-
reversible inhibitor
Filipin
-
slightly inhibiting at low concentration
Ketoconazole
-
-
methyl ([2-[(3S,8S,9S,10R,13S,14S,17R)-3-(acetyloxy)-10,13-dimethyl-2,3,4,7,8,9,10,11,12,13,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-17-yl]propyl]amino)acetate
Trypanosoma brucei subsp. rhodesiense
-
-
methyl 3-([2-[(3S,8S,9S,10R,13S,14S,17R)-3-(acetyloxy)-10,13-dimethyl-2,3,4,7,8,9,10,11,12,13,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-17-yl]propyl]amino)propanoate
Trypanosoma brucei subsp. rhodesiense
-
-
methyl 4-([2-[(3S,8S,9S,10R,13S,14S,17R)-3-(acetyloxy)-10,13-dimethyl-2,3,4,7,8,9,10,11,12,13,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-17-yl]propyl]amino)butanoate
Trypanosoma brucei subsp. rhodesiense
-
-
methyl 5-([2-[(3S,8S,9S,10R,13S,14S,17R)-3-(acetyloxy)-10,13-dimethyl-2,3,4,7,8,9,10,11,12,13,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-17-yl]propyl]amino)pentanoate
Trypanosoma brucei subsp. rhodesiense
-
-
methyl 6-([2-[(3S,8S,9S,10R,13S,14S,17R)-3-(acetyloxy)-10,13-dimethyl-2,3,4,7,8,9,10,11,12,13,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-17-yl]propyl]amino)hexanoate
Trypanosoma brucei subsp. rhodesiense
-
-
methyl 7-([2-[(3S,8S,9S,10R,13S,14S,17R)-3-(acetyloxy)-10,13-dimethyl-2,3,4,7,8,9,10,11,12,13,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-17-yl]propyl]amino)heptanoate
Trypanosoma brucei subsp. rhodesiense
-
-
Nystatin
-
slightly inhibiting at low concentration
S-adenosyl-L-homocysteine
-
-
S-adenosyl-L-homocysteine
-
uncompetitive with respect to S-adenosyl-L-methionine
S-isobutyladenosine
-
AdoMet analog, competitive inhibitor
Sinefungin
-
AdoMet analog, competitive inhibitor
sitosterol
-
-
Substrate analogues
-
dead-end inhibitors
-
Zymosterol
-
competitive versus sterol and S-adenosyl-L-methionine
methyl 8-([2-[(3S,8S,9S,10R,13S,14S,17R)-3-(acetyloxy)-10,13-dimethyl-2,3,4,7,8,9,10,11,12,13,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-17-yl]propyl]amino)octanoate
Trypanosoma brucei subsp. rhodesiense
-
-
additional information
-
overview, diverse substrate and transition state analogues
-
additional information
-
overview, diverse substrate and transition state analogues
-
additional information
Trypanosoma brucei subsp. brucei
Q45KX5
newly synthesized azasterols methyl ([2-[(3S,8S,9S,10R,13S,14S,17R)-3-(acetyloxy)-10,13-dimethyl-2,3,4,7,8,9,10,11,12,13,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-17-yl]propyl]amino)acetate, methyl 3-([2-[(3S,8S,9S,10R,13S,14S,17R)-3-(acetyloxy)-10,13-dimethyl-2,3,4,7,8,9,10,11,12,13,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-17-yl]propyl]amino)propanoate, methyl 4-([2-[(3S,8S,9S,10R,13S,14S,17R)-3-(acetyloxy)-10,13-dimethyl-2,3,4,7,8,9,10,11,12,13,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-17-yl]propyl]amino)butanoate, methyl 5-([2-[(3S,8S,9S,10R,13S,14S,17R)-3-(acetyloxy)-10,13-dimethyl-2,3,4,7,8,9,10,11,12,13,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-17-yl]propyl]amino)pentanoate, methyl 6-([2-[(3S,8S,9S,10R,13S,14S,17R)-3-(acetyloxy)-10,13-dimethyl-2,3,4,7,8,9,10,11,12,13,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-17-yl]propyl]amino)hexanoate, methyl 7-([2-[(3S,8S,9S,10R,13S,14S,17R)-3-(acetyloxy)-10,13-dimethyl-2,3,4,7,8,9,10,11,12,13,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-17-yl]propyl]amino)heptanoate, and methyl 8-([2-[(3S,8S,9S,10R,13S,14S,17R)-3-(acetyloxy)-10,13-dimethyl-2,3,4,7,8,9,10,11,12,13,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-17-yl]propyl]amino)octanoate, none show any significant inhibition against the recombinant enzyme
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
amphotericine B
-
activates at concentrations below 5.4 nM, optimal at 2.1 nM, wild-type and mutant
candicidin
-
stimulates, best at low concentration
Filipin
-
slightly activating at high concentration
Nystatin
-
slightly activating at high concentration
pimaricin
-
strong activation, activation level decreases with increasing concentration of pimaricin
glutathione
-
required
additional information
-
no cofactor requirement
-
KM VALUE [mM]
KM VALUE [mM] Maximum
SUBSTRATE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
0.033
-
14alpha-Methylzymosterol
-
-
0.03
-
24(28)-methylene lophenol
-
-
0.05
-
24(28)-methylene lophenol
-
mutant Y83F; wild-type
0.043
-
24,25-Dehydropollinastanol
-
-
0.019
-
24-methylenelanosterol
-
recombinant enzyme
-
0.019
-
26,27-dehydrolanosterol
-
pH 7.5, 37C, Vmax: 6 pmol/min
-
0.013
-
26,27-dehydrozymosterol
-
mutant E64L
0.015
0.017
26,27-dehydrozymosterol
-
wild-type
0.015
-
26,27-dehydrozymosterol
-
mutant D65L
0.017
-
26,27-dehydrozymosterol
-
mutant D79L
0.022
-
26,27-dehydrozymosterol
-
mutant E82L
0.022
-
26,27-dehydrozymosterol
-
wild-type
0.023
-
26,27-dehydrozymosterol
-
mutant Y81A; mutant Y81W
0.024
-
26,27-dehydrozymosterol
-
mutant Y81L; mutant Y81V
0.026
-
26,27-dehydrozymosterol
-
mutant Y81F
0.027
-
26,27-dehydrozymosterol
-
mutant Y81I
0.074
-
26,27-dehydrozymosterol
-
mutant E98L
0.036
-
31-Norcycloartenol
-
-
-
0.035
-
31-norlanosterol
-
pH 7.5, 37C, Vmax 45 pmol/min
0.016
-
AdoMet
-
mutant Tyr153Phe
0.017
-
AdoMet
-
mutant Tyr153Leu; wild-type
0.03
-
AdoMet
-
mutant Cys128Ser
0.13
-
Agnosterol
-
-
0.125
-
Cholesta-5,7,24-trienol
-
-
0.028
-
Cycloartenol
-
-
0.03
-
Cycloartenol
-
-
0.032
-
Cycloartenol
-
-
0.045
-
Cycloartenol
-
wild-type and mutants Y83F and Y83L
0.067
-
desmosterol
-
lanosta-7,24-dienol
0.236
-
desmosterol
-
-
0.281
-
desmosterol
-
-
0.0106
-
lanosterol
-
recombinant enzyme
0.028
-
lanosterol
-
-
0.0334
-
S-adenosyl-L-methionine
-
-
0.006
-
Zymosterol
-
mutant Y66F, pH not specified in the publication, 35C
0.01
-
Zymosterol
-
mutant Y177F, pH not specified in the publication, 35C
0.011
-
Zymosterol
-
pH 7.5, 32C, mutant enzyme H107L
0.017
-
Zymosterol
-
pH 7.5, 32C, mutant enzyme D189L; pH 7.5, 32C, mutant enzyme E224L; pH 7.5, 32C, wild-type enzyme
0.017
-
Zymosterol
-
mutant Y81F; mutant Y81W; wild-type
0.018
-
Zymosterol
-
mutant Y81A; mutant Y81L
0.02
-
Zymosterol
-
pH 7.5, 32C, mutant enzyme H238L
0.021
-
Zymosterol
-
mutant Y81I
0.024
-
Zymosterol
-
pH 7.5, 32C, mutant enzyme H199L
0.026
-
Zymosterol
-
mutant Y81V
0.03
-
Zymosterol
-
pH 7.5, 37C, Vmax 2 pmol/min
0.034
-
Zymosterol
-
pH 7.5, 32C, mutant enzyme E108L; pH 7.5, 32C, mutant enzyme E209L
0.036
-
Zymosterol
-
mutant Y208F, pH not specified in the publication, 35C
0.042
-
Zymosterol
-
pH 7.5, 32C, mutant enzyme E246L
0.047
-
Zymosterol
-
-
0.05
-
Zymosterol
-
pH 7.5, 30C
0.052
-
Zymosterol
-
-
0.055
0.075
Zymosterol
-
value depends on concentration of detergent
0.055
-
Zymosterol
-
wild-type, pH not specified in the publication, 35C
0.063
-
Zymosterol
-
-
0.063
-
Zymosterol
-
-
0.071
-
Zymosterol
-
-
0.038
-
lanosterol
-
pH 7.5, 37C, Vmax: 50 pmol/min
additional information
-
additional information
-
overview
-
additional information
-
additional information
-
-
-
additional information
-
additional information
-
overview
-
TURNOVER NUMBER [1/s]
TURNOVER NUMBER MAXIMUM[1/s]
SUBSTRATE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
0.001
-
24(28)-methylene lophenol
-
wild-type
0.005
-
24(28)-methylene lophenol
-
mutant Y83F
0.0001167
-
26,27-dehydrozymosterol
-
mutant Y81A; mutant Y81V
0.00025
-
26,27-dehydrozymosterol
-
mutant Y81I
0.0003333
-
26,27-dehydrozymosterol
-
mutant Y81L
0.0006667
-
26,27-dehydrozymosterol
-
wild-type
0.0008
-
26,27-dehydrozymosterol
-
-
0.0025
-
26,27-dehydrozymosterol
-
mutant Y81F
0.003333
-
26,27-dehydrozymosterol
-
mutant Y81W
0.003
-
AdoMet
-
mutant Tyr153Phe
0.005
-
AdoMet
-
mutant Cys128Ser
0.01
-
AdoMet
-
mutant Tyr153Leu; wild-type
0.01
-
Cycloartenol
-
wild-type and mutants Y83F and Y83L
0.01
-
Cycloartenol
-
-
0.0023
-
lanosterol
-
pH 7.5, 37C
0.0001
-
Zymosterol
-
pH 7.5, 32C, mutant enzyme H199L
0.0008333
-
Zymosterol
-
mutant Y81A
0.001
-
Zymosterol
-
mutant E98L
0.001167
-
Zymosterol
-
mutant Y81V
0.002
-
Zymosterol
-
pH 7.5, 32C, mutant enzyme E108L; pH 7.5, 32C, mutant enzyme E246L
0.003
-
Zymosterol
-
pH 7.5, 32C, mutant enzyme H107L
0.004167
-
Zymosterol
-
mutant Y81L
0.004333
-
Zymosterol
-
mutant Y81I
0.005
-
Zymosterol
-
mutants E82L and E64L
0.007
-
Zymosterol
-
mutant D65L
0.008
-
Zymosterol
-
pH 7.5, 32C, mutant enzyme D189L; pH 7.5, 32C, mutant enzyme E224L; pH 7.5, 32C, mutant enzyme H238L
0.009
-
Zymosterol
-
pH 7.5, 32C, mutant enzyme E209L
0.01
-
Zymosterol
-
-
0.01
-
Zymosterol
-
wild-type and mutant D79L
0.01
-
Zymosterol
-
mutant Y81F
0.01
-
Zymosterol
-
pH 7.5, 30C
0.01083
-
Zymosterol
-
wild-type
0.011
-
Zymosterol
-
pH 7.5, 32C, wild-type enzyme
0.013
-
Zymosterol
-
-
0.01333
-
Zymosterol
-
mutant Y81W
Ki VALUE [mM]
Ki VALUE [mM] Maximum
INHIBITOR
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
0.00001
-
(24,S),25-epiminozymosterol
-
-
0.000015
-
(24R)-24-methyl-25,26,27-trisnor-24-dimethylamino-N-oxide cycloartenol
-
-
0.00002
-
(24R)-24-methyl-25-azacycloartenol
-
-
0.0000017
-
(24R)-methyl-25-thiacholesteryl iodide
-
versus S-adenosyl-L-methionine
0.000003
-
(24R)-methyl-25-thiacholesteryl iodide
-
versus zymosterol
0.00001
-
(24R,S),25-epiminolanosterol
-
-
0.000085
-
(24R,S)-24-Ethyl-25-azacycloartenol
-
-
0.00005
-
(24R,S)-24-Methyl-25,26,27-trisnor-24-dimethylsulfonium cycloartenol iodide
-
-
0.000025
-
(24R,S)-24-Methyl-25,26,27-trisnor-24-trimethylarsonium cycloartenol iodide
-
-
0.00002
-
(24R,S)-24-Methyl-25-azacycloartenol
-
-
0.000045
-
(24S)-24-methyl-25,26,27-trisnor-24-dimethylamino-N-oxide cycloartenol
-
-
0.00003
-
(24S)-24-methyl-25-azacycloartenol
-
-
0.0000023
-
(24S)-methyl-25-thiacholesteryl iodide
-
versus S-adenosyl-L-methionine
0.0000046
-
(24S)-methyl-25-thiacholesteryl iodide
-
versus zymosterol
0.000016
-
(3beta,24,R,S)-24-methyl-24-thioniacholest-5-enol
-
-
0.00009
-
23-Azacholesterol
-
-
0.00009
-
24(28)-methylene cycloartanol
-
-
0.085
-
24(28)-methylenecycloartenol
-
-
0.000003
-
24(R,S),25-epiminolanosterol
-
-
0.000011
-
24(R,S),25-epiminolanosterol
-
pH 7.5, 30C
0.000049
-
24(R,S),25-epiminolanosterol
-
-
0.000025
-
24(R,S)-25-epiminolanosterol
-
wild-type
0.00013
-
24(R,S)-25-epiminolanosterol
-
mutant Y81A
0.000145
-
24(R,S)-25-epiminolanosterol
-
mutant Y81V
0.000165
-
24(R,S)-25-epiminolanosterol
-
mutant Y81I
0.00018
-
24(R,S)-25-epiminolanosterol
-
mutant Y81L
0.00031
-
24(R,S)-25-epiminolanosterol
-
mutant Y81F
0.00036
-
24(R,S)-25-epiminolanosterol
-
mutant Y81W
0.00018
-
24-Azacholesterol
-
-
0.00003
-
24-Azacycloartanyl acetate
-
-
0.000035
-
24-Methyl-25,26,27-trisnor-24-trimethylammonium cycloartenol iodide
-
-
0.00017
-
24-Oxo-25-azacycloartenol
-
-
0.000035
-
25,26,27-Trisnor-24-trimethylammonium cycloartenol iodide
-
-
0.00000125
-
25-Aza-24,25-dihydrozymosterol
-
-
0.000003
-
25-Aza-24,25-dihydrozymosterol
-
-
0.000048
-
25-azacholestane
-
-
0.000045
-
25-Azacholesterol
-
-
0.000015
-
25-Azacholesterol hydrochloride
-
-
0.000002
-
25-Azacycloartenol
-
-
0.000003
-
25-Azacycloartenol
-
-
0.000015
-
25-Azacycloartenol
-
-
0.00003
-
25-Azacycloartenol
-
-
0.000045
-
25-Azacycloartenol
-
-
0.00004
-
25-azacyloartenol
-
-
0.000014
-
25-azalanosterol
-
pH 7.5, 37C
-
0.00003
-
25-azalanosterol
-
wild-type
-
0.000039
-
25-azalanosterol
-
-
-
0.000045
-
25-azalanosterol
-
-
-
0.000054
-
25-azalanosterol
-
pH 7.5, 30C
-
0.00019
-
25-azalanosterol
-
mutant Y81A
-
0.000195
-
25-azalanosterol
-
mutant Y81V
-
0.000205
-
25-azalanosterol
-
mutant Y81I
-
0.00021
-
25-azalanosterol
-
mutant Y81L
-
0.00036
-
25-azalanosterol
-
mutant Y81F
-
0.00039
-
25-azalanosterol
-
mutant Y81W
-
0.0000011
-
25-thiacholesterol iodide
-
versus S-adenosyl-L-methionine
0.0000024
-
25-thiacholesterol iodide
-
versus zymosterol
0.000054
-
26,27-dehydrolanosterol
-
pH 7.5, 37C
-
0.000009
-
26,27-dehydrozymosterol
-
pH 7.5, 30C
0.0011
-
26,27-dehydrozymosterol
-
-
0.004
-
26,27-dehydrozymosterol
-
wild-type
0.007
-
26,27-dehydrozymosterol
-
mutant Y81V
0.009
-
26,27-dehydrozymosterol
-
mutant Y81I
0.01
-
26,27-dehydrozymosterol
-
mutant Y81F; mutant Y81W
0.011
-
26,27-dehydrozymosterol
-
mutant Y81A; mutant Y81L
0.029
-
26,27-dehydrozymosterol
-
-
0.022
-
5'-deoxy-5'-(methylthio)adenosine
-
-
0.072
-
cholesta-8,24(28)-dienol
-
pH 7.5, 30C
-
0.023
-
cyclolaudanol
-
-
0.009
-
desmosterol
-
versus S-adenosyl-L-methionine
0.0193
-
desmosterol
-
versus S-adenosyl-L-methionine
0.449
-
desmosterol
-
versus sterol
0.489
-
desmosterol
-
versus sterol
0.02
-
ergosta-5,7,22-trienol
-
pH 7.5, 30C
-
0.00071
-
ergosterol
-
mutant Y81A
0.000745
-
ergosterol
-
mutant Y81V
0.00077
-
ergosterol
-
mutant Y81I
0.00078
-
ergosterol
-
mutant Y81L
0.00082
-
ergosterol
-
mutant Y81F
0.00085
-
ergosterol
-
wild-type
0.00088
-
ergosterol
-
mutant Y81W
0.027
-
ergosterol
-
-
0.058
-
S-isobutyladenosine
-
-
0.013
-
Sinefungin
-
-
0.0001
-
sitosterol
-
-
0.00000000075
-
solasodine
-
-
0.0045
-
Zymosterol
-
versus S-adenosyl-L-methionine
0.022
-
Zymosterol
-
versus sterol
0.08
-
ergosterol
-
-
additional information
-
additional information
-
overview, diverse substrate and transition state analogues
-
additional information
-
additional information
-
overview, diverse substrate and transition state analogues
-
IC50 VALUE [mM]
IC50 VALUE [mM] Maximum
INHIBITOR
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
0.0035
-
22,26-azasterol
-
-
0.005
-
24(R,S),25-epiminolanosterol
-
pH 7.5, 30C
0.02
-
24-thialanosterol
-
pH 7.5, 30C
-
0.000014
-
25-azalanosterol
-
pH 7.5, 37C
-
0.003
-
25-azalanosterol
-
pH 7.5, 30C
-
0.00176
-
azasterol
Trypanosoma brucei subsp. brucei
Q45KX5
recombinant enzyme
0.00243
-
azasterol
Trypanosoma brucei subsp. brucei
Q45KX5
native enzyme
0.00383
-
Ketoconazole
-
-
SPECIFIC ACTIVITY [µmol/min/mg]
SPECIFIC ACTIVITY MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
0.00000082
-
Trypanosoma brucei subsp. brucei
Q45KX5
bloodstream forms
0.00000217
-
Trypanosoma brucei subsp. brucei
Q45KX5
procyclic forms
0.0008
-
-
purified enzyme
0.00124
-
-
purified enzyme
0.53
-
-
purified enzyme
additional information
-
-
activity at various concentrations of glutathione
additional information
-
-
-
additional information
-
-
comparison recombinant and wild-type
additional information
-
-
relative activity using 26,27-dehydrozymosterol as a substrate: wild-type 100%, mutant Y81F 300%, mutant Y81W 450%, mutant Y81I 25%, mutant Y81L 40%, mutant Y81V 15%, mutant Y81A 15%; relative activity using zymosterol as a substrate: wild-type 100%, mutant Y81F 92%, mutant Y81W 124%, mutant Y81I 32%, mutant Y81L 37%, mutant Y81V 8%, mutant Y81A 8%
additional information
-
P25087
prediction of secondary structure, eight residues at positions 79, 81, 82, 192, 217, 218, 219 and 223 critical for catalysis, scanning mutagenesis experiments involving a leucine replacement of 52 amino acids, substitution of key residues with functionally or structurally similar amino acids, 5 new residues at positions Y192, G217, G218, T219 and Y223 can switch the course of C1-transfer activity to include plant-like C2-transfer activity, model supported in which several conserved and non-conserved amino acids located in distinct regions regulate course of the C-methylation reaction toward product differences
additional information
-
A4IDL2, -
cloning of SMT gene, sequence homologies and Western Blot comparable between Leishmania donovani, Leishmania infantum and Leishmania major, serological evaluation revealed that SMT is recognized by visceral leishmaniasis (VL) patients, immunized mice shown to have lower parasite burdens in both spleens and livers compared with non-immunized mice or mice injected with adjuvant alone
pH OPTIMUM
pH MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
7.5
8
-
assay at
7.5
-
-
assay at
7.5
-
-
recombinant enzyme
7.5
-
P25087
assay at
7.5
-
-
assay at
7.5
-
-
-
7.5
-
-
assay at
7.6
-
-
assay at
pH RANGE
pH RANGE MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
5.5
10
-
slightly active at pH 5.5, no activity at pH 10
5.5
9
-
recombinant enzyme
6.5
-
-
half maximum velocities at 6.5 and 9.0
6.8
7.7
-
less than half-maximal activity above and below
9
-
-
half maximum velocities at 6.5 and 9.0
TEMPERATURE OPTIMUM
TEMPERATURE OPTIMUM MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
30
-
-
assay at
30
-
-
assay at
35
-
-
assay at
35
-
-
assay at
35
-
P25087
assay at
35
-
-
assay at
37
-
-
recombinant enzyme
TEMPERATURE RANGE
TEMPERATURE MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
15
30
-
less than half-maximal activity above and below
22
45
-
recombinant enzyme
SOURCE TISSUE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
SOURCE
-
weak expression, determined by RT-PCR
Manually annotated by BRENDA team
-
highest expression, determined by RT-PCR
Manually annotated by BRENDA team
-
weak expression, determined by RT-PCR
Manually annotated by BRENDA team
additional information
Trypanosoma brucei subsp. brucei
Q45KX5
approximately 3fold higher levels are present in procyclic forms than in bloodstream forms, existence of active enzyme in both forms of the parasite
Manually annotated by BRENDA team
additional information
-
expression of GhSMT2-1 is 10times higher than expression of GhSMT2-2
Manually annotated by BRENDA team
additional information
Trypanosoma brucei subsp. brucei 427
-
approximately 3fold higher levels are present in procyclic forms than in bloodstream forms, existence of active enzyme in both forms of the parasite
-
Manually annotated by BRENDA team
LOCALIZATION
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
-
by immunofluorescence and electron microscopy studies it is shown that sterol methenyltransferase is primarily associated to the endoplasmic reticulum. In addition to this localisation, the protein is incorporated into translucent vesicles presumably of the endocytic pathway
Manually annotated by BRENDA team
MOLECULAR WEIGHT
MOLECULAR WEIGHT MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
39800
-
A4IDL2, -
predicted from sequence, SDS-PAGE
40000
-
-
predicted from cDNA
42500
-
-
calculated from cDNA
43000
-
-
SDS-PAGE
150000
-
-
gel filtration
160000
-
-
wild-type and mutants Y83F and Y83L, gel filtration
160000
-
-
gel filtration
172000
-
-
gel filtration
178000
-
-
gel filtration
SUBUNITS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
tetramer
-
4 * 40000, SDS-PAGE
tetramer
-
4 * 43000, SDS-PAGE
additional information
-
cooperativity among the subunits
GENERAL STABILITY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
no stabilization by MgCl2, CaCl2, DTT, reduced glutathione, phosphatidylcholine
-
STORAGE STABILITY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
-70C, 1 month, less than 10% loss of activity
-
4C, 0.1 M Tris-HCl buffer, 1 mM Mg2+, 90% loss of activity overnight
-
Purification/COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
partial, recombinant from E. coli
-
using anion exchange chromatography, gel filtration and fast performance liquid chromatography using a Mono Q column
-
isoform SMT2-2 is purified to homogeneity by column chromatography, gel filtration
-
partial, recombinant from E. coli
-
recombinant protein, SDS-PAGE; using Ni-NTA-chromatography
A4IDL2, -
using Ni-NTA chromatography
-
gel filtration
P25087
recombinant mutant from E. coli; recombinant wild-type from E. coli
-
recombinant wild-type from E. coli
-
recombinant wild-type SMT is expressed and partially purified by anionic-exchange chromatography to generate ca. 85% pure Erg6p as determined by SDS-PAGE quantification of the target protein
-
wild-type and mutant enzymes
-
to homogeneity
-
Cloned/COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
expression in Escherichia coli
-
expression in Saccharomyces cerevisiae mutant line erg6, which is deleted in the SMT1 gene, complementation of the yeast
Q9LM02
expression as FLAG-fusion protein in Escherichia coli, amino acid sequence analysis
-
expression in Escherichia coli
-
overexpression of the pET vector in Escherichia coli BL21(DE3)
-
expressed as a His-tagged fusion protein in Escherichia coli; pET-28a vector, expressed in Escherichia coli Rosetta, recombinant protein
A4IDL2, -
coexpression of the catalytic domain of Hevea brasiliensis 3-hydroxy-3-methylglutaryl CoA reductase and Nicotiana tabacum C24-sterol methyltransferase type 1 in tobacco, under control of both constitutive and seed-specific promoters, resulting in increased accumulation of total sterol in seed tissue by 2.5fold and 2.1fold, respectively
-
expressed as a recombinant fusion protein in Escherichia coli BL21
-
expression in Escherichia coli, His-tagged protein
-
expressed in Escherichia coli; expressed in Escherichia coli, recombinant protein, site-directed mutagenesis
P25087
expression in Escherichia coli, wild-type and mutant enzymes
-
expression of exchange mutants in Escherichia coli; overexpression in Escherichia coli
-
overexpression in Escherichia coli
-
expressed in Escherichia coli
-
overexpressed in Escherichia coli HMS-174 cells
-
into pET28a(+) and expressed with a His tag at the amino terminus in Escherichia coli BL21(DE3)
Trypanosoma brucei subsp. brucei
Q45KX5
expression in Saccharomyces cerevisiae mutant line erg6, which is deleted in the C-24-sterol methyltransferase, via Escherichia coli, complementation of the yeast, amino acid sequence comparison
-
EXPRESSION
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
transcriptional regulation of soybean SMT2 genes is influenced by environmental conditions to some extent: analysis of transcript abundance by qRT-PCR reveals that both the genes SMT2-1 and SMT2-2 are down-regulated after dehydration and markedly induced under cold conditions. ABA treatment elicits an increase in transcript levels for both the genes. A reduction in expression is associated with the salinity treatment for both the genes
-
ENGINEERING
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
F82I
-
continues to catalyze strongly both the first and second C1-transfer activities and generates product sets similar to the control
F82L
-
first C1-transfer activity is relatively unaffected, loss of the second C1-transfer activity
F85L
-
first C1-transfer activity is relatively unaffected, loss of the second C1-transfer activity
F91L
-
first C1-transfer activity reduced from the control activity, loss of the second C1-transfer activity
F93L
-
first C1-transfer activity reduced from the control activity, loss of the second C1-transfer activity
W87L
-
first and second C1-transfer activities are greatly reduced from the control activities
Y83F
-
first C1-transfer activity is relatively unaffected whereas the second C1-transfer activity generates different amounts of product compared to the control
A193L
P25087
no activity; no enzyme activity
A193S
P25087
95% relative enzyme activity; relative activity: 95%
A196L
P25087
73% relative enzyme activity; relative activity: 73%
A200L
P25087
4% relative enzyme activity; relative activity: 4%
A221L
P25087
25% relative enzyme activity; relative activity: 25%
A350L
P25087
100% relative enzyme activity; relative activity: 100%
C128L
P25087
no activity; no enzyme activity
C128L
-
no activity with AdoMet as substrate, Kd (mM) (zymosterol): 0.005, Kd (mM) (AdoMet): 0.028, photolabelled: value below 1%
C128S
-
Km (mM) (substrate: AdoMet): 30, kcat (1/sec) (substrate: AdoMet): 0.005, Kd (mM) (zymosterol): 0.005, Kd (mM) (AdoMet): 0.008
C198L
P25087
95% relative enzyme activity; relative activity: 95%
C198V
P25087
16% relative enzyme activity; relative activity: 16%
D125L
-
inactive mutant
D125L
P25087
no activity
D125L
-
no activity with AdoMet as substrate, Kd (mM) (zymosterol): 0.006, Kd (mM) (AdoMet): 0.012, photolabelled: 30%
D152L
-
inactive mutant
D152L
P25087
no activity
D152L
-
no activity with AdoMet as substrate, Kd (mM) (zymosterol): 0.005, Kd (mM) (AdoMet): 0.014, photolabelled: 35%
D189L
-
the ratio of turnover-number to KM-value for zymosterol is 1.4fold lower than the wild-type ratio
D189L
P25087
relative activity: 91%
D229L
P25087
relative activity: 100%
D276L
-
inactive mutant
D276L
P25087
no activity
D65L
-
potentially responsible for substrate binding to leucine by site directed mutagenesis, unchanged activity
D65L
P25087
relative activity: 100%
D79L
-
potentially responsible for substrate binding to leucine by site directed mutagenesis, not decreased activity, 1 new activity to form 24-methylzymosterol from zymosterol
D79L
P25087
relative activity: 81%
E108L
-
the ratio of turnover-number to KM-value for zymosterol is 11fold lower than the wild-type ratio
E108L
P25087
relative activity: 34%
E195L
-
inactive mutant
E195L
P25087
no activity
E209L
-
the ratio of turnover-number to KM-value for zymosterol is 2.4fold lower than the wild-type ratio
E209L
P25087
relative activity: 79%
E224L
P25087
relative activity: 74%
E246L
-
the ratio of turnover-number to KM-value for zymosterol is 13.5fold lower than the wild-type ratio
E246L
P25087
relative activity: 6%
E64L
-
potentially responsible for substrate binding to leucine by site directed mutagenesis, unchanged activity
E64L
P25087
relative activity: 100%
E68L
-
potentially responsible for substrate binding to leucine by site directed mutagenesis, no activity
E68L
P25087
no activity
E82D
P25087
55% relative enzyme activity; relative activity: 55%
E82L
-
potentially responsible for substrate binding to leucine by site directed mutagenesis, not decreased activity, 1 new activity to form 24-methylzymosterol from zymosterol
E82L
-
produces plant-like substrate-product profiles
E82L
P25087
relative activity: 99%
E82Q
P25087
90% relative enzyme activity; relative activity: 90%
E98L
-
potentially responsible for substrate binding to leucine by site directed mutagenesis, unchanged activity
E98L
P25087
relative activity: 100%
F178L
P25087
34% relative enzyme activity; relative activity: 34%
F183L
P25087
100% relative enzyme activity
F188L
P25087
2% relative enzyme activity; relative activity: 2%
F220L
P25087
29% relative enzyme activity; relative activity: 29%
F269L
P25087
no activity; no enzyme activity
F357L
P25087
100% relative enzyme activity; relative activity: 100%
F89L
P25087
100% relative enzyme activity; relative activity: 100%
F91L
P25087
15% relative enzyme activity; relative activity: 15%
G127L
P25087
1% relative enzyme activity; relative activity: 1%
G129L
P25087
no activity; no enzyme activity
G131L
P25087
5% relative enzyme activity; relative activity: 5%
G132L
P25087
50% relative enzyme activity; relative activity: 50%
G217L
P25087
100% relative enzyme activity, mutant can perform C2-transfer activity to give 24-ethyl(idene)-sterols; relative activity: 100%
G218L
P25087
100% relative enzyme activity, mutant can perform C2-transfer activity to give 24-ethyl(idene)-sterols; relative activity: 100%
G347L
P25087
5% relative enzyme activity; relative activity: 5%
G351L
P25087
90% relative enzyme activity; relative activity: 90%
G352L
P25087
3% relative enzyme activity; relative activity: 3%
G84L
P25087
14% relative enzyme activity; relative activity: 14%
G86L
P25087
16% relative enzyme activity; relative activity: 16%
H107L
-
the ratio of turnover-number to KM-value for zymosterol is 2.4fold lower than the wild-type ratio
H107L
P25087
relative activity: 23%
H199L
-
the ratio of turnover-number to KM-value for zymosterol is 162fold lower than the wild-type ratio
H199L
P25087
relative activity: 2%
H199Q
P25087
45% relative enzyme activity; relative activity: 45%
H199R
P25087
20% relative enzyme activity; relative activity: 20%
H224L
-
the ratio of turnover-number to KM-value for zymosterol is 1.4fold lower than the wild-type ratio
H238L
-
the ratio of turnover-number to KM-value for zymosterol is 1.6fold lower than the wild-type ratio
H238L
P25087
relative activity: 85%
H90L
-
inactive mutant
H90L
P25087
no activity
H90Q
P25087
no activity; no enzyme activity
H90R
P25087
no activity; no enzyme activity
I194L
P25087
67% relative enzyme activity; relative activity: 67%
K215L
P25087
100% relative enzyme activity; relative activity: 100%
P133L
P25087
no activity; no enzyme activity
P133L
-
no activity with AdoMet as substrate, Kd (mM) (zymosterol): 0.015, Kd (mM) (AdoMet): no binding, photolabelled: value below 1%
P201L
P25087
58% relative enzyme activity; relative activity: 58%
P216L
P25087
65% relative enzyme activity; relative activity: 65%
S354L
P25087
100% relative enzyme activity; relative activity: 100%
S87E
P25087
100% relative enzyme activity
S87L
P25087
100% relative enzyme activity; relative activity: 100%
S87Q
P25087
100% relative enzyme activity
S88L
P25087
61% relative enzyme activity; relative activity: 61%
S88N
P25087
17% relative enzyme activity; relative activity: 17%
S97E
P25087
relative activity: 100%
S97Q
P25087
relative activity: 100%
T197L
P25087
93% relative enzyme activity; relative activity: 93%
T219L
P25087
32% relative enzyme activity, mutant can perform C2-transfer activity to give 24-ethyl(idene)-sterols
V126L
P25087
1% relative enzyme activity; relative activity: 1%
V130L
P25087
100% relative enzyme activity; relative activity: 100%
V222L
P25087
27% relative enzyme activity
V349L
P25087
47% relative enzyme activity; relative activity: 47%
W225F
P25087
100% relative enzyme activity; relative activity: 60%
W225L
P25087
100% relative enzyme activity; relative activity: 100%
W286F
P25087
100% relative enzyme activity; relative activity: 51%
W286L
P25087
2% relative enzyme activity; relative activity: 2%
W85F
P25087
100% relative enzyme activity; relative activity: 55%
W85L
P25087
40% relative enzyme activity; relative activity: 40%
Y153F
P25087
100% relative enzyme activity; relative activity: 41%
Y153F
-
Km (mM) (substrate: AdoMet): 0.016, kcat (1/sec) (substrate: AdoMet): 0.003, Kd (mM) (zymosterol): 0.007, Kd (mM) (AdoMet): 0.013, photolabelled: 55%
Y153L
P25087
no enzyme activity; relative activity: 100%
Y153L
-
Km (mM) (substrate: AdoMet): 0.017, kcat (1/sec) (substrate: AdoMet): 0.01, Kd (mM) (zymosterol): 0.004, Kd (mM) (AdoMet): 0.004
Y192F
P25087
100% relative enzyme activity, mutant can perform C2-transfer activity to give 24-ethyl(idene)-sterols
Y192L
P25087
95% relative enzyme activity
Y207F
P25087
100% relative enzyme activity; relative activity: 100%
Y207L
P25087
3% relative enzyme activity; relative activity: 3%
Y223F
P25087
100% relative enzyme activity, mutant can perform C2-transfer activity to give 24-ethyl(idene)-sterols; relative activity: 100%
Y223L
P25087
100% relative enzyme activity; relative activity: 100%
Y287L
P25087
20% relative enzyme activity; relative activity: 20%
Y74F
P25087
100% relative enzyme activity; relative activity: 100%
Y74L
P25087
100% relative enzyme activity; relative activity: 100%
Y81A
-
Km (mM): 0.018 (zymosterol), 0.023 (26,27-dehydrozymosterol), kcat (1/sec): 0.00083 (zymosterol), 0.000116 (26,27-dehydrozymosterol), Ki (mM): 0.011 (26,27-dehydrozymosterol), 0.00019 (25-azalanosterol), 0.00013 (24(R,S),25-epiminolanosterol), 0.071 (ergosterol)
Y81F
-
produces plant-like substrate-product profiles
Y81F
-
Km (mM): 0.017 (zymosterol), 0.026 (26,27-dehydrozymosterol), kcat (1/sec): 0.0108 (zymosterol), 0.0025 (26,27-dehydrozymosterol), Ki (mM): 0.010 (26,27-dehydrozymosterol), 0.00036 (25-azalanosterol), 0.00031 (24(R,S),25-epiminolanosterol), 0.082 (ergosterol)
Y81F
P25087
relative activity: 100%
Y81I
-
Km (mM): 0.021 (zymosterol), 0.027 (26,27-dehydrozymosterol), kcat (1/sec): 0.00433 (zymosterol), 0.00025 (26,27-dehydrozymosterol), Ki (mM): 0.009 (26,27-dehydrozymosterol), 0.00020 (25-azalanosterol), 0.00016 (24(R,S),25-epiminolanosterol), 0.077 (ergosterol)
Y81L
-
Km (mM): 0.018 (zymosterol), 0.024 (26,27-dehydrozymosterol), kcat (1/sec): 0.00416 (zymosterol), 0.00033 (26,27-dehydrozymosterol), Ki (mM): 0.011 (26,27-dehydrozymosterol), 0.00021 (25-azalanosterol), 0.00018 (24(R,S),25-epiminolanosterol), 0.078 (ergosterol)
Y81L
P25087
90% relative enzyme activity; relative activity: 90%
Y81V
-
Km (mM): 0.026 (zymosterol), 0.024 (26,27-dehydrozymosterol), kcat (1/sec): 0.00116 (zymosterol), 0.00011 (26,27-dehydrozymosterol), Ki (mM): 0.007 (26,27-dehydrozymosterol), 0.000195 (25-azalanosterol), 0.000145 (24(R,S),25-epiminolanosterol), 0.074 (ergosterol)
Y81W
-
Km (mM): 0.017 (zymosterol), 0.023 (26,27-dehydrozymosterol), kcat (1/sec): 0.0133 (zymosterol), 0.0033 (26,27-dehydrozymosterol), Ki (mM): 0.010 (26,27-dehydrozymosterol), 0.00039 (25-azalanosterol), 0.00036 (24(R,S),25-epiminolanosterol), 0.088 (ergosterol)
Y83F
P25087
95% relative enzyme activity; relative activity: 95%
Y83L
P25087
90% relative enzyme activity; relative activity: 90%
Y83W
P25087
100% relative enzyme activity; relative activity: 100%
Y177F
-
mutant proteins catalyses zymosterol much less efficiently than the wild-type enzyme, with a Vmax/Km ratio 23-40% that of wild-type
Y208F
-
mutant proteins catalyses zymosterol much less efficiently than the wild-type enzyme, with a Vmax/Km ratio 23-40% that of wild-type
Y66F
-
mutant proteins catalyses zymosterol much less efficiently than the wild-type enzyme, with a Vmax/Km ratio 23-40% that of wild-type. Sterol composition of the Y66F catalysis is different. The sterol mixture possesses a significant decrease in ergosta-8,24(25)-dienol compensated by an increase in ergosta-8,25(27)-dienol and ergosta-8,24(28)-dienol
additional information
-
overexpression of SMT2 gene in a mutant strain leads to an accumulation of sitosterol and to an altered phenotype, some of the changes can be restored by brassinosteroid treatment, some cannot, sterol profile of wild-type and mutant plants
additional information
Q9LM02
construction of SMT1-deficient mutants with altered phenotype, reduced fertility and root growth defects, transgenic plant seedlings are sensitive against brassinosteroids and transfection with a genomic clone or a SMT1 cDNA can complement the mutants
Y83L
-
first C1-transfer activity greatly reduced from the control activity, loss of the second C1-transfer activity
additional information
-
GhSMT2-1 and GhSMT2-2 have high homology with the SMT2 from Arabidopsis thaliana and Nicotiana tabacum. The typical conserved structures characterized by the sterol C-24 methyltransferase, such as region I (LDVGCGVGGPMRAI), region II (IEATCHAP), and region III (YEWGWGQSFHF), are present in both deduced proteins
additional information
-
natural amphotericine B-resistant mutant strain
additional information
A4IDL2, -
C57BL/6 mice immunized with a vaccine candidate consisting of 24-c-methyltransferase as an antigene formulated monophosphoryl lipid A (MPL-SE) show Ag-specific Th1 immune responses characterized by robust production of IFN-gamma upon specific Ag re-exposure in vitro. Upon challenge with Leishmania infantum, mice immunized with SMT plus MPL-SE show significant lower parasite burdens in both spleens and livers compared with non-immunized mice or mice injected with adjuvant alone
additional information
-
Leishmania major promastigotes cells overproducing the enzyme do not have increased resistance to the sterol methenyltransferase inhibitor 22,26-azasterol
K353L
P25087
56% relative enzyme activity
additional information
P25087
scanning mutagenesis experiments involving a leucine replacement of 52 amino acids in Erg6p followed by substitution of key residues with functionally or structurally similar amino acids indicate that 5 new residues at positions Y192, G217, G218, T219 and Y223 can switch the course of C1-transfer activity to include plant-like C2-transfer activity. The data support a model in which several conserved and non-conserved amino acids located in distinct regions of the Saccharomyces cerevisiae Erg6p regulate the course of the C-methylation reaction toward product differences
additional information
-
by photoaffinity labeling and mutational analysis the AdoMet binding site is defined. Results indicate that one or both of Cys128 and Pro133 are covalently bound to AdoMet
APPLICATION
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
agriculture
-
construction of transgenic plants with modified sterol profile via recombinant sterol 24-C-methyltransferase shall protect crops against damage by insect infestation
degradation
-
the amino acids of Region 1 provide a tight substrate orientation imposed by hydrophobic interactions between the sterol side chain and the SMT active site contacts and control the production and processing of the transmethylation pathways governed by the first and second C1-transfer activities
agriculture
-
construction of transgenic plants with modified sterol profile via recombinant sterol 24-C-methyltransferase shall protect crops against damage by insect infestation
medicine
A4IDL2, -
the results indicate that SMT/MPL-SE can be an effective vaccine candidate for use against visceral leishmaniasis; vaccine development, visceral leishmaniasis
medicine
-
SMT is a vaccine antigen for multiple forms of leishmaniasis
medicine
-
target for drug development against pneumonitis caused by this pathogen based on its unique substrate preference for lanosterol and 24-methylenelanosterol
agriculture
-
construction of transgenic plants with modified sterol profile via recombinant sterol 24-C-methyltransferase shall protect crops against damage by insect infestation
synthesis
-
rational drug target design based on structure-function-relation
agriculture
-
construction of transgenic plants with modified sterol profile via recombinant sterol 24-C-methyltransferase shall protect crops against damage by insect infestation
degradation
-
active site of the yeast SMT has the necessary amino acids to generate products common to SMT catalysis of plants and protozoa, minor perturbations in the active site topography brought about by mutagenesis are sufficient to recognize new substrates
drug development
-
inhibition studies as a powerful approach to rational design of new anti-sleeping sickness chemotherapeutic drugs
drug development
Trypanosoma brucei subsp. brucei
Q45KX5
newly synthesized azasterol derivates act at sites other than 24-SMT in Trypanosoma brucei
drug development
Trypanosoma brucei subsp. brucei 427
-
newly synthesized azasterol derivates act at sites other than 24-SMT in Trypanosoma brucei
-
drug development
Trypanosoma brucei subsp. rhodesiense
-
newly synthesized azasterol derivates act at sites other than 24-SMT in Trypanosoma brucei
drug development
Trypanosoma brucei subsp. rhodesiense STIB900
-
newly synthesized azasterol derivates act at sites other than 24-SMT in Trypanosoma brucei
-