Information on EC 2.3.1.50 - serine C-palmitoyltransferase

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The enzyme appears in viruses and cellular organisms

EC NUMBER
COMMENTARY
2.3.1.50
-
RECOMMENDED NAME
GeneOntology No.
serine C-palmitoyltransferase
REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
palmitoyl-CoA + L-serine = CoA + 3-dehydro-D-sphinganine + CO2
show the reaction diagram
mechanism
-
palmitoyl-CoA + L-serine = CoA + 3-dehydro-D-sphinganine + CO2
show the reaction diagram
ordered bi-bi mechanism
-
palmitoyl-CoA + L-serine = CoA + 3-dehydro-D-sphinganine + CO2
show the reaction diagram
mechanism
-
palmitoyl-CoA + L-serine = CoA + 3-dehydro-D-sphinganine + CO2
show the reaction diagram
formation of the external aldimine intermediate
-
palmitoyl-CoA + L-serine = CoA + 3-dehydro-D-sphinganine + CO2
show the reaction diagram
using 1HNMR the exchange of the alpha-proton of L-serine with the solvent in the presence and absence of S-(2- oxoheptadecyl)-CoA, the structural analogue of palmitoyl-CoA is investagated. Results demonstrate the presence of substrate synergism, in which the alpha-proton of L-serine is activated by the binding of the second substrate palmitoyl-CoA
-
palmitoyl-CoA + L-serine = CoA + 3-dehydro-D-sphinganine + CO2
show the reaction diagram
via reaction intermediate pyridoxal 5'-phosphate-L-serine aldimine, His138 changes its hydrogen bond partner from the carboxyl group of L-serine to the carbonyl group of palmitoyl-CoA upon the binding of palmitoyl-CoA, making the L-serine CaH bond perpendicular to the pyridoxal 5'-phosphate-Schiff base plane, reaction mechanism with substrate synergism in the SPT reaction, overview. Modelling of reaction intermediates
A7BFV6, -
palmitoyl-CoA + L-serine = CoA + 3-dehydro-D-sphinganine + CO2
show the reaction diagram
the enzyme forms a pyridoxal 5'-phosphate-L-serine-aldimine intermediate during the reaction, His159 plays multiple roles in the reaction mechanism by exploiting the stereochemistry of Dunathans conjecture. His159 promotes both the Claisen-type condensation as an acid catalyst and the protonation at Calpha of the second quinonoid to form the pyridoxal 5'-phosphate-KDS aldimine, spectral analysis, overview
-
palmitoyl-CoA + L-serine = CoA + 3-dehydro-D-sphinganine + CO2
show the reaction diagram
the enzyme forms an external aldimine intermediate, as well as dunathan and quinoid intermediates, followed by external beta-keto acid intermediate, and finally product quinoid and product external aldimine intermediates, reaction cycle, overview
-
palmitoyl-CoA + L-serine = CoA + 3-dehydro-D-sphinganine + CO2
show the reaction diagram
the enzyme forms an external aldimine intermediate, as well as dunathan and quinoid intermediates, and followed by external beta-keto acid intermediate, and finally product quinoid and product external aldimine intermediates, reaction cycle, overview
Q93UV0
palmitoyl-CoA + L-serine = CoA + 3-dehydro-D-sphinganine + CO2
show the reaction diagram
via reaction intermediate pyridoxal 5'-phosphate-L-serine aldimine, His138 changes its hydrogen bond partner from the carboxyl group of L-serine to the carbonyl group of palmitoyl-CoA upon the binding of palmitoyl-CoA, making the L-serine CaH bond perpendicular to the pyridoxal 5'-phosphate-Schiff base plane, reaction mechanism with substrate synergism in the SPT reaction, overview. Modelling of reaction intermediates
Sphingobacterium multivorum GTC97
-
-
palmitoyl-CoA + L-serine = CoA + 3-dehydro-D-sphinganine + CO2
show the reaction diagram
ordered bi-bi mechanism; the enzyme forms an external aldimine intermediate, as well as dunathan and quinoid intermediates, and followed by external beta-keto acid intermediate, and finally product quinoid and product external aldimine intermediates, reaction cycle, overview
Sphingomonas paucimobilis EY2395
-
-
palmitoyl-CoA + L-serine = CoA + 3-dehydro-D-sphinganine + CO2
show the reaction diagram
-
-
-
-
REACTION TYPE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
Acyl group transfer
-
-
-
-
Claisen condensation
-
-
condensation
-
-
condensation
-
-
condensation
Sphingomonas paucimobilis EY2395
-
-
-
decarboxylation
-
-
-
-
PATHWAY
KEGG Link
MetaCyc Link
ceramide de novo biosynthesis
-
Metabolic pathways
-
sphingolipid biosynthesis (plants)
-
sphingolipid biosynthesis (yeast)
-
Sphingolipid metabolism
-
SYSTEMATIC NAME
IUBMB Comments
palmitoyl-CoA:L-serine C-palmitoyltransferase (decarboxylating)
A pyridoxal-phosphate protein.
SYNONYMS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
3-oxosphinganine synthetase
-
-
-
-
acyl-CoA:serine C-2 acyltransferase decarboxylating
-
-
-
-
palmitoyltransferase, serine
-
-
-
-
serine palmitoyl transferase
-
-
serine palmitoyl transferase
-
-
serine palmitoyltransferase
-
-
-
-
serine palmitoyltransferase
-
-
serine palmitoyltransferase
Q6K8E7
-
serine palmitoyltransferase
Q9LSZ9
-
serine palmitoyltransferase
A7BFV8
-
serine palmitoyltransferase
B2XR73
-
serine palmitoyltransferase
-
-
serine palmitoyltransferase
-
-
serine palmitoyltransferase
O15269
-
serine palmitoyltransferase
O15270 AND Q9NUV7
-
serine palmitoyltransferase
-
-
serine palmitoyltransferase
B3Y000, B3Y9H2
-
serine palmitoyltransferase
-
-
serine palmitoyltransferase
-
-
serine palmitoyltransferase
A7BFV6
-
serine palmitoyltransferase
Sphingobacterium multivorum GTC97
A7BFV6
-
-
serine palmitoyltransferase
A7BFV7
-
serine palmitoyltransferase
-
-
serine palmitoyltransferase
Q93UV0
-
serine palmitoyltransferase
Sphingomonas paucimobilis EY2395
-, Q93UV0
-
-
serine palmitoyltransferase
-
-
serine palmitoyltransferase 1
-
-
serine-palmitoyl transferase
-
-
serine-palmitoyltransferase
-
-
-
-
serine-palmitoyltransferase
-
-
SPT
-
-
-
-
SPT
B3Y000, B3Y9H2
-
SPT
Sphingobacterium multivorum GTC97
A7BFV6
-
-
SPT
Sphingomonas paucimobilis EY2395
-, Q93UV0
-
-
additional information
-
the amount of enzyme activity in microsomes is inversely correlated with the amount of the major coat Gag protein of the L-A dsRNA virus particles
additional information
-
SPT belongs to the fold type I family of the pyridoxal 5'-phosphate-dependent enzymes, and the alpha-oxamine synthase subfamily enzymes
CAS REGISTRY NUMBER
COMMENTARY
62213-50-7
-
ORGANISM
COMMENTARY
LITERATURE
SEQUENCE CODE
SEQUENCE DB
SOURCE
Bacteroides melaninogenicus
-
-
-
Manually annotated by BRENDA team
LCB2; ssp. chinensis
UniProt
Manually annotated by BRENDA team
infects the globally important marine calcifying microalga Emiliania huxleyi, gene ehv050
-
-
Manually annotated by BRENDA team
genetically corrected revertant strain LY-B/cLCB1 of deficient mutant LY-B; mutant defective strain LY-B
-
-
Manually annotated by BRENDA team
mutant defective strain LY-B
-
-
Manually annotated by BRENDA team
two subunits of SPT, Sptlc1 and Sptlc2, i.e. LCB1 and LCB2 or SPT1 and SPT2
-
-
Manually annotated by BRENDA team
cv. early profilic straightneck
-
-
Manually annotated by BRENDA team
-
SwissProt
Manually annotated by BRENDA team
4 distinct SPT isozymes
-
-
Manually annotated by BRENDA team
; gene hLCB1 and hLCB2
-
-
Manually annotated by BRENDA team
gene hLCB1
SwissProt
Manually annotated by BRENDA team
gene hLCB2
SwissProt
Manually annotated by BRENDA team
human SPT1
SwissProt
Manually annotated by BRENDA team
human SPT2
SwissProt
Manually annotated by BRENDA team
isozymes SPT1 and SPT2
-
-
Manually annotated by BRENDA team
patiens with hereditary sensory neuropathy type I
-
-
Manually annotated by BRENDA team
SPT contains subunits SPTLC1-SPTLC3
-
-
Manually annotated by BRENDA team
subunit 2 and 3
O15270 AND Q9NUV7
UniProt
Manually annotated by BRENDA team
subunits SPT1 and SPT2
SwissProt
Manually annotated by BRENDA team
gene mLCB2
-
-
Manually annotated by BRENDA team
subunit LCB1 fragment; two genes encoding the LCB2 and LCB1 subunits of the enzyme
UniProt
Manually annotated by BRENDA team
subunit LCB2; two genes encoding the LCB2 and LCB1 subunits of the enzyme
UniProt
Manually annotated by BRENDA team
isozyme SPT2
-
-
Manually annotated by BRENDA team
Sprague-Dawley rats
-
-
Manually annotated by BRENDA team
gene LCB1/SCS1
-
-
Manually annotated by BRENDA team
genes LCB1/TSC2, LCB2/TSC1, TSC3
-
-
Manually annotated by BRENDA team
lcb1 and lcb2
-
-
Manually annotated by BRENDA team
Sphingobacterium multivorum GTC97
strain GTC97
UniProt
Manually annotated by BRENDA team
strain EY2395
-
-
Manually annotated by BRENDA team
strain EY2395
SwissProt
Manually annotated by BRENDA team
Sphingomonas paucimobilis EY2395
EY2395
-
-
Manually annotated by BRENDA team
Sphingomonas paucimobilis EY2395
strain EY2395
-
-
Manually annotated by BRENDA team
Sphingomonas paucimobilis EY2395
strain EY2395
SwissProt
Manually annotated by BRENDA team
GENERAL INFORMATION
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
malfunction
-
IRS1 serine phosphorylation and PKCtheta recruitment to the plasma membrane are increased in cells with reduced SPT expression and activity. Short-term inhibition of SPT ameliorates palmitate/ceramide-induced insulin resistance, sustained loss/reduction in SPT expression/activity promotes greater partitioning of palmitate towards diacylglycerol synthesis, which impacts negatively upon IRS1-directed insulin signalling
malfunction
-
mutations in human SPT cause hereditary sensory autonomic neuropathy type 1, HSAN1, a disease characterized by loss of feeling in extremities and severe pain
malfunction
O15269
mutations in the SPTLC1 subunit associated with hereditary sensory and autonomic neuropathy type I
metabolism
-
SPT is the key regulator enzyme in the ceramide de novo biosynthesis pathway
metabolism
A7BFV6, -
SPT is a key enzyme of sphingolipid biosynthesis and catalyses the pyridoxal 5'-phosphate-dependent decarboxylative condensation reaction of L-serine with palmitoyl-CoA to generate 3-ketodihydrosphingosine
metabolism
-
SPT catalyzes the first and rate-limiting step of the sphingolipid biosynthetic pathway
metabolism
-
SPT catalyzes the first and rate-limiting step of the sphingolipid biosynthetic pathway
metabolism
-
SPT catalyzes the rate-limiting step in the de novo synthesis of sphingolipids, subunit SPTLC3 generates C16-sphingoid bases, and sphingolipids with a C16 backbone constitute a significant proportion of human plasma sphingolipids
metabolism
-
SPT catalyzes the first and rate-limiting step in the de novo synthesis of sphingolipids
metabolism
-
SPT catalyzes the first committed step in sphingolipid biosynthesis
metabolism
Sphingobacterium multivorum GTC97
-
SPT is a key enzyme of sphingolipid biosynthesis and catalyses the pyridoxal 5'-phosphate-dependent decarboxylative condensation reaction of L-serine with palmitoyl-CoA to generate 3-ketodihydrosphingosine
-
physiological function
-
SPT plays a crucial role in lipid-induced insulin resistance in skeletal muscle cells by desensitizing muscle cells to insulin in response to incubation with palmitate, overview. The effect is antagonized by inhibition of protein kinase C
physiological function
-
the enzyme is required for ceramide synthesis as key regulatory enzyme of this pathway, major mechanism for ceramide generation in NR8383 macrophages is stimulation of their de novo synthesis
physiological function
O15269
in the endoplasmic reticulum subunit SPT1 is responsible for de novo sphingolipid biosynthesis, it is also present in other cellular compartments, including focal adhesions where it is associated with cell morphology
physiological function
B3Y000, B3Y9H2, -
the enzyme is required for resistance against pathogen Pseudomonas cichorii. The gene for the LCB2 subunit of SPT is a potent inducer of hypersensitive response-like cell death involving pyridoxal 5'-phosphate; the enzyme is required for resistance against pathogen Pseudomonas cichorii. The gene for the LCB2 subunit of SPT is a potent inducer of hypersensitive response-like cell death involving pyridoxal 5'-phosphate
physiological function
B2XR73
the LCB2 subunit of the sphingolipid biosynthesis enzyme SPT can function as an attenuator of the hypersensitive response and Bax-induced cell death, not involved in the dominant-negative effect that results from BcLCB2 overexpression, overview
SUBSTRATE
PRODUCT                      
REACTION DIAGRAM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
(Substrate)
LITERATURE
(Substrate)
COMMENTARY
(Product)
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
acyl-CoA + L-serine
CoA + ?
show the reaction diagram
-
-
-
-
?
arachidoyl-CoA + L-serine
CoA + 2-amino-1-hydroxydocosan-3-one + CO2
show the reaction diagram
-
37% activity compared to that with palmitoyl-CoA
-
-
?
elaidoyl-CoA + L-serine
CoA + 2-amino-1-hydroxy-trans-11-eicosen-3-one + CO2
show the reaction diagram
-
39% activity compared to that with palmitoyl-CoA
-
-
?
L-alanine + palmitoyl-CoA
CoA + (2S)-2-aminooctadecan-3-one + CO2
show the reaction diagram
-
-
-
-
?
L-alanine + stearoyl-CoA
CoA + (2S)-2-aminoicosan-3-one + CO2
show the reaction diagram
-
-
-
-
?
L-serine + palmitoyl-CoA
CoA + 3-dehydro-D-shinganine + CO2
show the reaction diagram
-
-
-
-
?
L-serine + palmitoyl-CoA
CoA + 3-dehydro-D-sphinganine + CO2
show the reaction diagram
-
-
-
-
?
L-serine + palmitoyl-CoA
CoA + 3-dehydro-D-sphinganine + CO2
show the reaction diagram
O15270 AND Q9NUV7
-
-
-
?
L-serine + stearoyl-CoA
CoA + (2S)-2-amino-1-hydroxyicosan-3-one + CO2
show the reaction diagram
-
-
-
-
?
myristoleoyl-CoA + L-serine
CoA + 2-amino-1-hydroxy-cis-11-hexadecen-3-one + CO2
show the reaction diagram
-
46% activity compared to that with palmitoyl-CoA
-
-
?
myristoyl-CoA + L-serine
CoA + 2-amino-1-hydroxyhexadecan-3-one + CO2
show the reaction diagram
Sphingomonas paucimobilis, Sphingomonas paucimobilis EY2395
-
75% activity compared to that with palmitoyl-CoA
-
-
?
myristoyl-CoA + L-serine
CoA + 2-amino-1-hydroxy-cis-11-hexadecen-3-one + CO2
show the reaction diagram
-
SPT is the first and rate-limiting enzyme of sphingolipid biosynthesis, the viral enzyme exhibits preference for myristoyl-CoA rather than palmitoyl-CoA
-
-
?
myristoyl-CoA + L-serine
CoA + ? + CO2
show the reaction diagram
-
-, recombinant SPTLC3 subunit in HEK-293 cells
-
-
?
n-heptadecanoyl-CoA + L-serine
CoA + 2-amino-1-hydroxynonadecan-3-one + CO2
show the reaction diagram
Sphingomonas paucimobilis, Sphingomonas paucimobilis EY2395
-
75% activity compared to that with palmitoyl-CoA
-
-
?
oleoyl-CoA + L-serine
CoA + 2-amino-1-hydroxy-11-cis-eicosen-3-one + CO2
show the reaction diagram
-
57% activity compared to that with palmitoyl-CoA
-
-
?
palmitoleoyl-CoA + L-serine
CoA + 2-amino-1-hydroxy-cis-11-octadecen-3-one + CO2
show the reaction diagram
Sphingomonas paucimobilis, Sphingomonas paucimobilis EY2395
-
80% activity compared to that with palmitoyl-CoA
-
-
?
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
show the reaction diagram
-
-
-
-
?
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
show the reaction diagram
-
-
-
?
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
show the reaction diagram
-
-
-
-
?
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
show the reaction diagram
-
-
-
?
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
show the reaction diagram
-
-
-
-
?
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
show the reaction diagram
O15269, O15270
-
-
-
-
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
show the reaction diagram
-
-
-
?
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
show the reaction diagram
-
-
-
?
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
show the reaction diagram
-
-
-
-
?
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
show the reaction diagram
O15269
-
-
-
?
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
show the reaction diagram
-
-
-
-
?
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
show the reaction diagram
-
-
-
-
?
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
show the reaction diagram
-
-
-
ir
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
show the reaction diagram
-
-
-
-
?
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
show the reaction diagram
-
-
-
?
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
show the reaction diagram
-
-
-
-
ir
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
show the reaction diagram
-
-
-
ir
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
show the reaction diagram
-
-
-
-
?
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
show the reaction diagram
-
-
-
ir
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
show the reaction diagram
-
-
-
-
-
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
show the reaction diagram
-
-
-
ir
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
show the reaction diagram
-
-
-
-
ir
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
show the reaction diagram
Bacteroides melaninogenicus
-
-
-
-
-
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
show the reaction diagram
Bacteroides melaninogenicus
-
-
-
-
ir
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
show the reaction diagram
O15269, O15270
-
-
-
ir
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
show the reaction diagram
Q93UV0, -
-
-
?
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
show the reaction diagram
-
-
-
-
?
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
show the reaction diagram
Q93UV0
-
-
-
?
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
show the reaction diagram
Q9LSZ9
-
-
-
?
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
show the reaction diagram
A7BFV6, -
-
-
-
?
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
show the reaction diagram
A7BFV6, -
-
-
-
?
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
show the reaction diagram
A7BFV7, -
-
-
-
?
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
show the reaction diagram
A7BFV8, -
-
-
-
?
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
show the reaction diagram
-
-
i.e. 2-amino-1-hydroxyoctadecane-3-one, i.e. 3-oxo-dihydroxysphingosine
ir
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
show the reaction diagram
-
palmitoyl-CoA is the preferred substrate
-
-
?
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
show the reaction diagram
-
palmitoyl-CoA is the preferred substrate
-
-
ir
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
show the reaction diagram
-
palmitoyl-CoA is the preferred substrate
-
?
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
show the reaction diagram
-
palmitoyl-CoA is the preferred substrate, optimal palmitoyl-CoA concentration is 0.2 mM
-
ir
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
show the reaction diagram
-
activities are greatest with palmitoyl-CoA and palmitelaidoyl-CoA, followed by fully saturated homologs, activity considerably diminishes as the alkyl-chain length increases or decreases, or with the presence of a cis-double bond
-
-
?
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
show the reaction diagram
-
no other amino acids can substitute for serine
-
-
ir
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
show the reaction diagram
-
no other amino acids can substitute for serine
-
?
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
show the reaction diagram
-
palmitoyl-CoA is used in preference to other saturated or unsaturated acyl-CoA substrates
-
-
?
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
show the reaction diagram
-
palmitoyl-CoA is used in preference to other saturated or unsaturated acyl-CoA substrates
-
ir
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
show the reaction diagram
-
involved in cellular stress response
-
-
?
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
show the reaction diagram
-
first step of biosynthesis of sphingolipid bases
-
-
?
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
show the reaction diagram
-
first step of biosynthesis of sphingolipid bases
-
?
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
show the reaction diagram
-
first step of biosynthesis of sphingolipid bases
-
-
?
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
show the reaction diagram
O15269, O15270
first step of biosynthesis of sphingolipid bases
-
-
-
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
show the reaction diagram
-
first step of biosynthesis of sphingolipid bases
-
?
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
show the reaction diagram
-
first step of biosynthesis of sphingolipid bases
-
-
?
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
show the reaction diagram
-
first step of biosynthesis of sphingolipid bases
-
-
-
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
show the reaction diagram
-
first step of biosynthesis of sphingolipid bases
-
ir
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
show the reaction diagram
-
first step of biosynthesis of sphingolipid bases
-
-
?
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
show the reaction diagram
-
first step of biosynthesis of sphingolipid bases
-
ir
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
show the reaction diagram
O15269, O15270
rate-limiting enzyme in synthesis of sphingolipids
-
-
-
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
show the reaction diagram
-
rate-limiting enzyme in synthesis of sphingolipids
-
?
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
show the reaction diagram
-
rate-limiting enzyme in synthesis of sphingolipids
-
-
?
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
show the reaction diagram
Q93UV0, -
rate-limiting enzyme in synthesis of sphingolipids
-
?
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
show the reaction diagram
O15269, O15270
initial step of de novo ceramide biosynthesis
-
-
-
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
show the reaction diagram
-
initial step of de novo ceramide biosynthesis
-
-
?
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
show the reaction diagram
-
initial step of de novo ceramide biosynthesis
-
ir
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
show the reaction diagram
-
initial step of de novo ceramide biosynthesis
-
-
?
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
show the reaction diagram
Saccharomyces cerevisiae, Bacteroides melaninogenicus
-
initial step of de novo ceramide biosynthesis
-
ir
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
show the reaction diagram
-
key enzyme of sphingolipid metabolism
-
-
?
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
show the reaction diagram
-
the enzyme catalyzes the initial and rate-limiting step in de novo sphingolipid synthesis. Potential role for overexpression of SPT in processes of cell metastasis
-
-
?
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
show the reaction diagram
-
key enzyme in ceramide synthesis, overview
-
-
?
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
show the reaction diagram
-
SPT is the first and rate-limiting enzyme of sphingolipid biosynthesis
-
-
?
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
show the reaction diagram
Q9LSZ9
step in the sphingolipid biosynthetic pathway, overview
-
-
?
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
show the reaction diagram
-
the enzyme catalyses the first step in the ceramide biosynthesis pathway
-
-
?
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
show the reaction diagram
-
the enzyme catalyses the rate limiting step for the de novo synthesis of sphingolipids
-
-
?
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
show the reaction diagram
-
the enzyme catalyses the rate limiting step for the de novo synthesis of sphingolipids
-
-
?
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
show the reaction diagram
-
the enzyme catalyses the rate limiting step for the de novo synthesis of sphingolipids, the dynamic composition of the SPT complex could provide a cellular mechanism to adjust SPT activity to tissue specific requirements in sphingolipid synthesis
-
-
?
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
show the reaction diagram
-
the enzyme is involved in the ceramide metabolism, overview
-
-
?
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
show the reaction diagram
-
the viral enzyme exhibits preference for myristoyl-CoA rather than palmitoyl-CoA
-
-
?
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
show the reaction diagram
-
first and rate-limiting step in the de novo synthesis of sphingolipids
-
-
?
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
show the reaction diagram
-
His159 is the anchoring site for L-serine and regulates the alpha-deprotonation of L-serine by fixing the conformation of the pyridoxal 5'-phosphate-L-serine aldimine to prevent unwanted side reactions
-
-
?
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
show the reaction diagram
Sphingobacterium multivorum GTC97
A7BFV6
-
-
-
?
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
show the reaction diagram
Sphingomonas paucimobilis EY2395
-
palmitoyl-CoA is the preferred substrate, no other amino acids can substitute for serine
-
?
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
show the reaction diagram
Sphingomonas paucimobilis EY2395
Q93UV0
-
-
-
?
palmitoyl-CoA + L-serine
3-dehydrosphinganine + CoA + CO2
show the reaction diagram
-
-
-
-
?
S-(2-oxoheptadecyl)-CoA + L-serine
CoA + ?
show the reaction diagram
-
-
-
-
?
stearoyl-CoA + L-serine
CoA + 2-amino-1-hydroxyeicosan-3-one + CO2
show the reaction diagram
-
51% activity compared to that with palmitoyl-CoA
-
-
?
stearoyl-CoA + L-serine
(2S)-2-amino-1-hydroxyicosan-3-one + CoA + CO2
show the reaction diagram
-
-
-
-
?
lauroyl-CoA + L-serine
CoA + 2-amino-1-hydroxytetradecan-3-one + CO2
show the reaction diagram
-
18% activity compared to that with palmitoyl-CoA
-
-
?
additional information
?
-
-
specificity
-
-
-
additional information
?
-
-
increasing the acyl-CoA chain length above C16 by 1 or 2 carbons is less detrimental to activity than similar decrements in chain length
-
-
-
additional information
?
-
-
44% reduction of SPT activity in patiens with hereditary sensory neuropathy type I with mutation T399G in the SPTLC1 gene. However the decrease in SPT activity has no effect on de novo sphingolipid biosynthesis, cellular sphingolipid content, cell proliferation and death. Despite the inhibition of mutant allele, the activity of nonmutant allele of SPT may be sufficient for adequate sphingolipid biosynthesis and cell viability. The neurodegeneration in HSN1 is likely to be caused by subtler and rather long-term effects of these mutations such as loss of a cell-type selective facet of sphingolipid metabolism and/or function, or perhaps accumulation of toxic species, including abnormal proteins
-
-
-
additional information
?
-
-
elevation of ceramide in serum lipoproteins during acute phase response to inflammation is accompanied by activation of serine-palmitoyl transferase in liver
-
-
-
additional information
?
-
-
mutations in the enzyme subunit SPTLC1 cause hereditary sensory and autonomic neuropathy type I, HSAN1, an adult onset, autosomal dominant neuropathy, HSAN1 patients have reduced SPT activity, link between mutant SPT and neuronal dysfunction
-
-
-
additional information
?
-
-
stearoyl-CoA desaturase-1 deficiency, SCD1 deficiency, reduces ceramide synthesis by downregulating SPT and increasing beta-oxidation in skeletal muscle
-
-
-
additional information
?
-
-
the enzyme activity and expression in the heart is not affected by high-fat feeding
-
-
-
additional information
?
-
-
the expression of two SPT isoforms could be a cellular mechanism to adjust SPT activity to tissue-specific requirements of sphingolipid synthesis
-
-
-
additional information
?
-
-
the viral single-chain enzyme might form multiprotein complexes in vivo with functions different from the monomer, acyl-CoA substrate specificity, overview
-
-
-
additional information
?
-
B2XR73
the LCB2 subunit of the sphingolipid biosynthesis enzyme SPT can function as an attenuator of the hypersensitive response and Bax-induced cell death, overview
-
-
-
additional information
?
-
-
ability of the ssSPT subunits to modulate the chain lengths of LCBs in mammalian cells
-
-
-
additional information
?
-
-
assay optimization measuring radio-labeled L-serine incorporation into 3-oxodihydrosphingosine in microsomes or crude cell lysate, usage of an nonradioactive HPLC-based detection protocol, overview
-
-
-
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
myristoyl-CoA + L-serine
CoA + 2-amino-1-hydroxy-cis-11-hexadecen-3-one + CO2
show the reaction diagram
-
SPT is the first and rate-limiting enzyme of sphingolipid biosynthesis
-
-
?
myristoyl-CoA + L-serine
CoA + ? + CO2
show the reaction diagram
-
recombinant SPTLC3 subunit in HEK-293 cells
-
-
?
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
show the reaction diagram
-
-
-
-
?
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
show the reaction diagram
-
-
-
-
?
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
show the reaction diagram
O15269
-
-
-
?
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
show the reaction diagram
-
-
-
-
?
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
show the reaction diagram
-
-
-
-
?
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
show the reaction diagram
-
-
-
ir
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
show the reaction diagram
-
-
-
-
?
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
show the reaction diagram
-
-
-
ir
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
show the reaction diagram
-
-
-
-
?
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
show the reaction diagram
-
-
-
ir
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
show the reaction diagram
-
-
-
ir
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
show the reaction diagram
O15269, O15270
-
-
-
ir
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
show the reaction diagram
Q93UV0
-
-
-
?
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
show the reaction diagram
A7BFV6, -
-
-
-
?
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
show the reaction diagram
-
involved in cellular stress response
-
-
?
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
show the reaction diagram
-
first step of biosynthesis of sphingolipid bases
-
-
?
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
show the reaction diagram
-
first step of biosynthesis of sphingolipid bases
-
?
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
show the reaction diagram
-
first step of biosynthesis of sphingolipid bases
-
-
?
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
show the reaction diagram
O15269, O15270
first step of biosynthesis of sphingolipid bases
-
-
-
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
show the reaction diagram
-
first step of biosynthesis of sphingolipid bases
-
?
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
show the reaction diagram
-
first step of biosynthesis of sphingolipid bases
-
-
?
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
show the reaction diagram
-
first step of biosynthesis of sphingolipid bases
-
-
-
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
show the reaction diagram
-
first step of biosynthesis of sphingolipid bases
-
ir
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
show the reaction diagram
-
first step of biosynthesis of sphingolipid bases
-
-
?
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
show the reaction diagram
-
first step of biosynthesis of sphingolipid bases
-
ir
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
show the reaction diagram
O15269, O15270
rate-limiting enzyme in synthesis of sphingolipids
-
-
-
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
show the reaction diagram
-
rate-limiting enzyme in synthesis of sphingolipids
-
?
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
show the reaction diagram
-
rate-limiting enzyme in synthesis of sphingolipids
-
-
?
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
show the reaction diagram
Q93UV0, -
rate-limiting enzyme in synthesis of sphingolipids
-
?
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
show the reaction diagram
O15269, O15270
initial step of de novo ceramide biosynthesis
-
-
-
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
show the reaction diagram
-
initial step of de novo ceramide biosynthesis
-
-
?
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
show the reaction diagram
-
initial step of de novo ceramide biosynthesis
-
ir
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
show the reaction diagram
-
initial step of de novo ceramide biosynthesis
-
-
?
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
show the reaction diagram
Saccharomyces cerevisiae, Bacteroides melaninogenicus
-
initial step of de novo ceramide biosynthesis
-
ir
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
show the reaction diagram
-
key enzyme of sphingolipid metabolism
-
-
?
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
show the reaction diagram
-
the enzyme catalyzes the initial and rate-limiting step in de novo sphingolipid synthesis. Potential role for overexpression of SPT in processes of cell metastasis
-
-
?
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
show the reaction diagram
-
key enzyme in ceramide synthesis, overview
-
-
?
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
show the reaction diagram
-
SPT is the first and rate-limiting enzyme of sphingolipid biosynthesis
-
-
?
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
show the reaction diagram
Q9LSZ9
step in the sphingolipid biosynthetic pathway, overview
-
-
?
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
show the reaction diagram
-
the enzyme catalyses the first step in the ceramide biosynthesis pathway
-
-
?
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
show the reaction diagram
-
the enzyme catalyses the rate limiting step for the de novo synthesis of sphingolipids
-
-
?
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
show the reaction diagram
-
the enzyme catalyses the rate limiting step for the de novo synthesis of sphingolipids
-
-
?
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
show the reaction diagram
-
the enzyme catalyses the rate limiting step for the de novo synthesis of sphingolipids, the dynamic composition of the SPT complex could provide a cellular mechanism to adjust SPT activity to tissue specific requirements in sphingolipid synthesis
-
-
?
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
show the reaction diagram
-
the enzyme is involved in the ceramide metabolism, overview
-
-
?
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
show the reaction diagram
-
first and rate-limiting step in the de novo synthesis of sphingolipids
-
-
?
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
show the reaction diagram
Sphingobacterium multivorum GTC97
A7BFV6
-
-
-
?
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
show the reaction diagram
Sphingomonas paucimobilis EY2395
Q93UV0
-
-
-
?
additional information
?
-
-
44% reduction of SPT activity in patiens with hereditary sensory neuropathy type I with mutation T399G in the SPTLC1 gene. However the decrease in SPT activity has no effect on de novo sphingolipid biosynthesis, cellular sphingolipid content, cell proliferation and death. Despite the inhibition of mutant allele, the activity of nonmutant allele of SPT may be sufficient for adequate sphingolipid biosynthesis and cell viability. The neurodegeneration in HSN1 is likely to be caused by subtler and rather long-term effects of these mutations such as loss of a cell-type selective facet of sphingolipid metabolism and/or function, or perhaps accumulation of toxic species, including abnormal proteins
-
-
-
additional information
?
-
-
elevation of ceramide in serum lipoproteins during acute phase response to inflammation is accompanied by activation of serine-palmitoyl transferase in liver
-
-
-
additional information
?
-
-
mutations in the enzyme subunit SPTLC1 cause hereditary sensory and autonomic neuropathy type I, HSAN1, an adult onset, autosomal dominant neuropathy, HSAN1 patients have reduced SPT activity, link between mutant SPT and neuronal dysfunction
-
-
-
additional information
?
-
-
stearoyl-CoA desaturase-1 deficiency, SCD1 deficiency, reduces ceramide synthesis by downregulating SPT and increasing beta-oxidation in skeletal muscle
-
-
-
additional information
?
-
-
the enzyme activity and expression in the heart is not affected by high-fat feeding
-
-
-
additional information
?
-
-
the expression of two SPT isoforms could be a cellular mechanism to adjust SPT activity to tissue-specific requirements of sphingolipid synthesis
-
-
-
additional information
?
-
-
the viral single-chain enzyme might form multiprotein complexes in vivo with functions different from the monomer
-
-
-
additional information
?
-
B2XR73
the LCB2 subunit of the sphingolipid biosynthesis enzyme SPT can function as an attenuator of the hypersensitive response and Bax-induced cell death, overview
-
-
-
COFACTOR
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
pyridoxal 5'-phosphate
-
pyridoxal 5'-phosphate can be resolved from the enzyme by dialysis
pyridoxal 5'-phosphate
-
a pyridoxal phosphate protein
pyridoxal 5'-phosphate
-
stimulates
pyridoxal 5'-phosphate
-
stimulates
pyridoxal 5'-phosphate
-
bound to epsilon-amino group of a lysine residue in the active site
pyridoxal 5'-phosphate
-
required for activity
pyridoxal 5'-phosphate
-
-
pyridoxal 5'-phosphate
-
required for activity
pyridoxal 5'-phosphate
-
-
pyridoxal 5'-phosphate
A7BFV8, -
-
pyridoxal 5'-phosphate
A7BFV7, -
-
pyridoxal 5'-phosphate
-
-
pyridoxal 5'-phosphate
-
dependent on, the re face of SPT of the pyridoxal 5'-phosphate-Lys aldimine is occupied by a His159 residue instead of an aromatic amino acid residue as in the other type I enzymes
pyridoxal 5'-phosphate
-
dependent on
pyridoxal 5'-phosphate
Q93UV0
dependent on, bound at the active site at the dimer interface
pyridoxal 5'-phosphate
-
all subunits contain a pyridoxal 5'-phosphate consensus motif sequence
pyridoxal 5'-phosphate
B3Y000, B3Y9H2, -
the pyridoxal 5'-phosphate binding site is required for the LCB2 gene cell death inducing function; the pyridoxal 5'-phosphate binding site is required for the LCB2 gene cell death inducing function
pyridoxal 5'-phosphate
B2XR73
subunit LCB2 possesses a binding site
pyridoxal 5'-phosphate
-
-
METALS and IONS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
Mg2+
-
-
Mn2+
-
-
additional information
-
NaCl, LiCl, MgCl2, MnCl2 have no effect on activity
INHIBITORS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
(2S,3R)-2-amino-12-hydroxy-2-hydroxymethyl-3-sulfooxy-octadecanoic acid
-
IC50: 5.4 nM
(2S,3R)-2-amino-12-[(Z)-hydroxyimino]-2-hydroxymethyl-3-sulfooxy-octadecanoic acid
-
IC50: 30 nM
(2S,3R)-2-amino-3,12-dihydroxy-2-hydroxymethyl-octadecanoic acid
-
IC50: 3.2 nM
(2S,3R)-2-amino-3-hydroxy-2-hydroxymethyl-12-oxo-octadecanoic acid
-
IC50: 3.5 nM
(2S,3R)-2-amino-3-hydroxy-2-hydroxymethyl-12-oxo-octadecanoic acid methyl ester
-
IC50: 17 nM
3-hydroxypropionate
-
competitive to L-serine
4-amino-3-isoxazolidone
-
D-cycloserine and L-cycloserine are inhibitors, L-cycloserine is 14-fold more effective than D-cycloserine
-
alpha-methyl-DL-serine
-
competitive to L-serine
beta-chloro-L-alanine
-
in vivo, time dependent
beta-chloro-L-alanine
-
rapid, irreversible and time dependent inhibition at the active site; stereospecific, no inhibition by beta-chloro-D-alanine; suicide substrate
beta-chloro-L-alanine
-
mechanism-based inhibition
beta-chloro-L-alanine
-
cytotoxic, irreversible
beta-chloro-L-alanine
-
-
beta-chloro-L-alanine
-
-
beta-chloro-L-alanine
-
-
beta-chloro-L-alanine
-
irreversible
beta-Haloalanines
-
-
-
ceramide 1-phosphate
-
from bovine brain, inhibits the enzyme and blocks apoptosis in alveolar macrophages, overview
cis-4-methylsphingosine
-
time- and concentration-dependent, causes drastic morphological changes of the cells in vivo
cis-5-methylsphingosine
-
weak inhibition
cis-sphingosine
-
weak inhibition
cysteine
-
competitive to L-serine
L-alanine
-
inhibition of serine utilization
L-Cycloserine
-
mechanism-based inhibition
L-Cycloserine
-
cytotoxic, irreversible
L-Cycloserine
-
-
L-Cycloserine
-
irreversible
myriocin
-
i.e. sphingofungin B; strong inhibition, reversible by sphingosine
myriocin
-
in vivo intraperitoneal application to apolipoprotein E knockout mice leads to inhibition of atherosclerosis while feeding a high fat diet to the mice, and is associated with reduced plasma glycosphingolipid concentration and reduction of lesions in aorta regions, overview
myriocin
-
; the inhibition of SPT in hyperlipidemic apolipoprotein E knockout mice lowers plasma sphingolipids and atherogenic plasma lipids leading to the regression of pre-existing atherosclerotic lesions and to the formation of a stable plaque phenotype
myriocin
-
an SPT inhibitor
myriocin
B3Y000, B3Y9H2, -
inhibits the enzyme and inhibits defense response against a nonhost pathogen; inhibits the enzyme and inhibits defense response against a nonhost pathogen
myriocin
B2XR73
a potent inhibitor of SPT, that has no effect on Bax-induced programmed cell death
O-phosphoserine
-
competitive to L-serine
palmitoyl CoA
A7BFV8, -
enzyme shows remarkable substrate inhibition at palmitoyl-CoA concentrations higher than 0.1 nM
palmitoyl-CoA
-
0.5-1.0 mM, substrate inhibition
palmitoyl-CoA
-
no inhibition at concentrations up to 10 mM
palmitoyl-CoA
-
causes substrate inhibition at higher concentrations
serine methylester
-
competitive to L-serine
sulfamisterin
-
antibiotic derived from Pycnidiella sp., IC50: 3 nM
thermozymocidin
-
i.e. ISP-1; strong inhibition, reversible by sphingosine
threonine
-
competitive to L-serine
trans-4-methylsphingosine
-
-
trans-5-methylsphingosine
-
weak inhibition
additional information
-
not inhibited by halide ions
-
additional information
O15269, O15270
time-dependent degradation of enzyme mRNA by etoposide, activation of enzyme activity on protein level, time-dependent; time-dependent degradation of enzyme mRNA by etoposide, activation of enzyme activity on protein level, time-dependent
-
additional information
-
recombinant expression of C133W mutant SPTLC1 in cell cultures dominantly inhibits the endogenous SPT activity
-
additional information
-
the enzyme activity and expression in the heart is not affected by high-fat feeding
-
additional information
-
short-term inhibition of SPT ameliorates palmitate/ceramide-induced insulin resistance, sustained loss/reduction in SPT expression/activity promotes greater partitioning of palmitate towards diacylglycerol synthesis, which impacts negatively upon IRS1-directed insulin signalling
-
additional information
-
no inhibition by sucrose monolaurate
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
dithiothreitol
-
required for enzyme activity
dithiothreitol
-
required for enzyme activity
EDTA
-
required for enzyme activity
etoposide
O15269, O15270
; activates enzyme activity, but decreases mRNA level, time-dependent; activates enzyme activity, but decreases mRNA level, time-dependent
etoposide
-
enhanced activity due to chemotherapy with epotoside as therapeutic agent in Molt-4 leukemic cells
pioglitazone
-
increases the enzyme activity in vitro and in vivo independent of standard or high-fat diet
retinoic acid
-
up-regulates enzyme activity in embryonic carcinoma cell ine PCC7-Mz1
S-(2-oxoheptadecyl)-CoA
A7BFV6, -
binds to the smSPT-external aldimine complex and enhances the exchange rate of the alpha-proton of L-serine by smSPT
fenretinide
-
up-regulates enzyme activity in neuroblastoma cells
additional information
-
enzyme activity is enhanced under stress and in apoptosis, e.g. in pancreatic cells in a model for diabetes, in case of angiotensin II type receptor occupancy
-
additional information
-
increased SPT enzyme activity in reactive astrocytes of the hippocampus at 2 weeks post-kainate injection
-
additional information
-
the enzyme activity and expression in the heart is not affected by high-fat feeding
-
KM VALUE [mM]
KM VALUE [mM] Maximum
SUBSTRATE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
9.6
-
L-alanine
-
C133W mutant protein, pH not specified in the publication, temperature not specified in the publication
0.1
1
L-serine
-
-
0.4
-
L-serine
-
-
0.67
-
L-serine
-
-
0.75
-
L-serine
-
wild type protein, pH not specified in the publication, temperature not specified in the publication
0.78
-
L-serine
-
pH not specified in the publication, temperature not specified in the publication
1.2
-
L-serine
-
pH 8.0, 37C, microsomes
1.4
-
L-serine
Q93UV0
pH 7.5, 37C, recombinant wild-type enzyme
1.4
-
L-serine
-
C133W mutant protein, pH not specified in the publication, temperature not specified in the publication
1.6
-
L-serine
Q93UV0
pH 7.5, 37C, recombinant mutant N100W
1.8
-
L-serine
-
-
2.4
-
L-serine
Q93UV0
pH 7.5, 37C, recombinant mutant R378N
2.5
-
L-serine
Q93UV0
pH 7.5, 37C, recombinant mutant N100Y
3.5
-
L-serine
-
mutant DELTA2-9SPT
3.7
-
L-serine
A7BFV8, -
-
3.8
-
L-serine
Q93UV0
pH 7.5, 37C, recombinant mutant R378A
4.2
-
L-serine
-
native enzyme
4.8
-
L-serine
A7BFV6, -
-
6.2
-
L-serine
-
wild-type
7
-
L-serine
Q93UV0
pH 7.5, 37C, recombinant mutant N100C
0.03
-
myristoyl-CoA
-
pH 8.0, 37C, recombinant SPTLC3
0.019
-
palmitoyl-CoA
Q93UV0
pH 7.5, 37C, recombinant mutant N100W
0.0234
-
palmitoyl-CoA
-
pH not specified in the publication, temperature not specified in the publication
0.031
-
palmitoyl-CoA
Q93UV0
pH 7.5, 37C, recombinant mutant N100Y; pH 7.5, 37C, recombinant mutant R378N
0.035
-
palmitoyl-CoA
Q93UV0
pH 7.5, 37C, recombinant wild-type enzyme
0.039
-
palmitoyl-CoA
Q93UV0
pH 7.5, 37C, recombinant mutant R378A
0.04
-
palmitoyl-CoA
-
pH 8.0, 37C, recombinant SPTLC3
0.06
-
palmitoyl-CoA
Q93UV0
pH 7.5, 37C, recombinant mutant N100C
0.1
-
palmitoyl-CoA
A7BFV6, -
-
0.39
-
palmitoyl-CoA
A7BFV7, -
-
0.87
-
palmitoyl-CoA
-
native and recombinant enzyme
1
-
palmitoyl-CoA
-
wild-type
1.2
-
palmitoyl-CoA
-
mutant DELTA2-9SPT
0.0129
-
stearoyl-CoA
-
pH not specified in the publication, temperature not specified in the publication
additional information
-
L-alanine
-
wild-type enzyme does not utilize alanine efficiently
10.6
-
L-serine
-
recombinant enzyme
additional information
-
additional information
-
kinetics analysis, detailed overview
-
additional information
-
additional information
-
kinetics of the recombinant SPTLC3 subunit in HEK-293 cells, overview
-
additional information
-
additional information
-
Michaelis-Menten kinetics
-
TURNOVER NUMBER [1/s]
TURNOVER NUMBER MAXIMUM[1/s]
SUBSTRATE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
0.005
-
L-serine
Q93UV0
recombinant mutant N100Y
0.009
-
L-serine
Q93UV0
recombinant mutant N100W
0.033
-
L-serine
Q93UV0
recombinant mutant R378N
0.078
-
L-serine
Q93UV0
recombinant mutant R378A
0.25
-
L-serine
Q93UV0
recombinant mutant N100C
1.15
-
L-serine
Q93UV0
recombinant wild-type enzyme
0.005
-
palmitoyl-CoA
Q93UV0
recombinant mutant N100Y
0.009
-
palmitoyl-CoA
Q93UV0
recombinant mutant N100W
0.03
-
palmitoyl-CoA
A7BFV8, -
-
0.033
-
palmitoyl-CoA
Q93UV0
recombinant mutant R378N
0.0388
-
palmitoyl-CoA
-
-
0.0503
-
palmitoyl-CoA
-
recombinant enzyme
0.0687
-
palmitoyl-CoA
-
pH not specified in the publication, temperature not specified in the publication
0.078
-
palmitoyl-CoA
Q93UV0
recombinant mutant R378A
0.12
-
palmitoyl-CoA
A7BFV6, -
-
0.15
-
palmitoyl-CoA
A7BFV7, -
-
0.25
-
palmitoyl-CoA
Q93UV0
recombinant mutant N100C
1.15
-
palmitoyl-CoA
Q93UV0
recombinant wild-type enzyme
0.083
-
stearoyl-CoA
-
pH not specified in the publication, 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
0.002
-
L-serine
Q93UV0
pH 7.5, 37C, recombinant mutant N100Y
12405
0.006
-
L-serine
Q93UV0
pH 7.5, 37C, recombinant mutant N100W
12405
0.014
-
L-serine
Q93UV0
pH 7.5, 37C, recombinant mutant R378N
12405
0.021
-
L-serine
Q93UV0
pH 7.5, 37C, recombinant mutant R378A
12405
0.036
-
L-serine
Q93UV0
pH 7.5, 37C, recombinant mutant N100C
12405
0.0881
-
L-serine
-
pH not specified in the publication, temperature not specified in the publication
12405
0.821
-
L-serine
Q93UV0
pH 7.5, 37C, recombinant wild-type enzyme
12405
2.936
-
palmitoyl-CoA
-
pH not specified in the publication, temperature not specified in the publication
15192
6.416
-
stearoyl-CoA
-
pH not specified in the publication, temperature not specified in the publication
16707
Ki VALUE [mM]
Ki VALUE [mM] Maximum
INHIBITOR
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
2
-
L-alanine
-
wild type protein, substrate serine, pH and temperature not specified in the publication
5
-
L-alanine
-
C133W mutant protein, substrate serine, pH and temperature not specified in the publication
IC50 VALUE [mM]
IC50 VALUE [mM] Maximum
INHIBITOR
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
0.0000054
-
(2S,3R)-2-amino-12-hydroxy-2-hydroxymethyl-3-sulfooxy-octadecanoic acid
-
IC50: 5.4 nM
0.00003
-
(2S,3R)-2-amino-12-[(Z)-hydroxyimino]-2-hydroxymethyl-3-sulfooxy-octadecanoic acid
-
IC50: 30 nM
0.0000032
-
(2S,3R)-2-amino-3,12-dihydroxy-2-hydroxymethyl-octadecanoic acid
-
IC50: 3.2 nM
0.0000035
-
(2S,3R)-2-amino-3-hydroxy-2-hydroxymethyl-12-oxo-octadecanoic acid
-
IC50: 3.5 nM
0.000017
-
(2S,3R)-2-amino-3-hydroxy-2-hydroxymethyl-12-oxo-octadecanoic acid methyl ester
-
IC50: 17 nM
0.000003
-
sulfamisterin
-
antibiotic derived from Pycnidiella sp., IC50: 3 nM
SPECIFIC ACTIVITY [µmol/min/mg]
SPECIFIC ACTIVITY MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
0.000018
-
-
HEK cell extract
0.000044
-
-
HEK cells transfected with mLCB2, crude extract
0.0000465
-
-
activity in microsomes
0.000063
-
-
-
0.00011
-
-
substrate alanine, C133W mutant protein, pH not specified in the publication, temperature not specified in the publication
0.00027
-
-
-
0.000275
-
-
substrate serine, C133W mutant protein, pH not specified in the publication, temperature not specified in the publication
0.00135
-
-
substrate serine, wild type protein, pH not specified in the publication, temperature not specified in the publication
0.057
0.084
-
-
0.7
-
-
purified enzyme
additional information
-
-
assay method
additional information
-
-
-
additional information
-
-
-
additional information
-
-
activity in wild-type and tsc3 mutants
additional information
-
-
intramuscular fatty acid composition and ceramide content of wild-type and SCD1-deficiency mice, overview
additional information
-
-
increased enzymatic activity of SPT in reactive astrocytes of the hippocampus after kainate injections is shown; quantitation of ceramide or sphingomyelin
additional information
-
-
enzyme activty and ceramide synthesis in macrophages, overview
pH OPTIMUM
pH MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
7.4
-
-
assay at
7.4
-
-
assay at
7.5
-
Q93UV0
assay at
8.1
-
-
assay at
8.2
-
-
-
8.3
-
-
assay at
8.3
-
-
assay at
8.3
-
O15269, O15270
assay at; assay at
8.3
-
-
assay at
8.3
-
-
about, assay at
8.3
-
-
assay at
pH RANGE
pH RANGE MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
6.7
8.6
-
about 50% of activity maximum at pH 6.7 and pH 8.6
7
8
A7BFV8, -
-
TEMPERATURE OPTIMUM
TEMPERATURE OPTIMUM MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
25
-
-
assay at
30
-
-
assay at
37
-
-
assay at
37
-
O15269, O15270
assay at; assay at
37
-
-
assay at
37
-
-
assay at
37
-
Q93UV0
assay at
37
-
-
assay at
SOURCE TISSUE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
SOURCE
-
increased SPT enzyme activity in reactive astrocytes of the hippocampus at 2 weeks post-kainate injection
Manually annotated by BRENDA team
-
embryonic cell line PCC7-Mz1
Manually annotated by BRENDA team
O15269, O15270
leukemia Molt-4 cells; leukemia Molt-4 cells; leukemia Molt-4 cells
Manually annotated by BRENDA team
-
leukemia Molt-4 cells; neuroblastoma cell line
Manually annotated by BRENDA team
-
granule cells, neuronal cells
Manually annotated by BRENDA team
O15269, O15270
Purkinje cells; Purkinje cells
Manually annotated by BRENDA team
-
the cell shows very low enzyme activity due to deficiency of subunit LCB1
Manually annotated by BRENDA team
-
strong overexpression of both SPT subunits
Manually annotated by BRENDA team
O15269, O15270
vascular; vascular
Manually annotated by BRENDA team
-
protein expression of SPT in both psoriatic epidermis and non-lesional epidermis is investigated. Expression of SPT in psoriatic epidermis is significantly less than that of the non-lesional epidermis, which is inversely correlated with PASI score
Manually annotated by BRENDA team
O15269, O15270
except for ovarian epithelium; except for ovarian epithelium
Manually annotated by BRENDA team
-
proliferating, neonatal, dermal
Manually annotated by BRENDA team
Q6K8E7, Q9LSZ9
expression of LCB1; expression of LCB2
Manually annotated by BRENDA team
B2XR73
expression of LCB2
Manually annotated by BRENDA team
-
age-dependent amount of enzyme activity
Manually annotated by BRENDA team
-
isozyme SPT2
Manually annotated by BRENDA team
-
very low SPTLC3 content
Manually annotated by BRENDA team
-
increased expression of SPT in reactive astrocytes of the hippocampus after kainate injections is shown; increased SPT enzyme activity in reactive astrocytes of the hippocampus at 2 weeks post-kainate injection
Manually annotated by BRENDA team
-
human embryonic kidney cell line HEK 293
Manually annotated by BRENDA team
Q6K8E7, Q9LSZ9
young, expression of LCB1; young, expression of LCB2
Manually annotated by BRENDA team
B2XR73
young, expression of LCB2
Manually annotated by BRENDA team
-
strong overexpression of both SPT subunits
Manually annotated by BRENDA team
-
elevation of ceramide in serum lipoproteins during acute phase response to inflammation is accompanied by activation of serine-palmitoyl transferase in liver
Manually annotated by BRENDA team
-
from patients with hereditary sensory neuropathy type I
Manually annotated by BRENDA team
O15269, O15270
mucosal from colon, lung, prostate, stomach, thyroid, uterus, vascular tissue; mucosal from colon, lung, prostate, stomach, thyroid, uterus, vascular tissue
Manually annotated by BRENDA team
O15269, O15270
pyramidal, cytoplasm; pyramidal, cytoplasm
Manually annotated by BRENDA team
-
strong overexpression of both SPT subunits
Manually annotated by BRENDA team
-
strong overexpression of both SPT subunits
Manually annotated by BRENDA team
-
high SPTLC3 content
Manually annotated by BRENDA team
Q6K8E7, Q9LSZ9
expression of LCB1; expression of LCB2
Manually annotated by BRENDA team
B2XR73
expression of LCB2
Manually annotated by BRENDA team
-
strong overexpression of both SPT subunits
Manually annotated by BRENDA team
Q6K8E7, Q9LSZ9
expression of LCB1; expression of LCB2
Manually annotated by BRENDA team
B2XR73
expression of LCB2
Manually annotated by BRENDA team
-
strong overexpression of both SPT subunits
Manually annotated by BRENDA team
-
high SPTLC3 content
Manually annotated by BRENDA team
additional information
O15269, O15270
not in neuronal cells like astrocytes, microglia, and oligodendritic cells, not in skin and heart; not in neuronal cells like astrocytes, microglia, and oligodendritic cells, not in skin and heart
Manually annotated by BRENDA team
additional information
Q9LSZ9
ubiquitous expression of subunits LCB1 and LCB2 in the plant
Manually annotated by BRENDA team
additional information
Q6K8E7, Q9LSZ9
AtLCB1 is expressed ubiquitously in all organs of Arabidopsis thaliana examined, but the transcript level is higher in flowers and stems than in leaves and roots; AtLCB2 is expressed ubiquitously in all organs of Arabidopsis thaliana examined, but the transcript level is higher in flowers and stems than in leaves and roots
Manually annotated by BRENDA team
additional information
B2XR73
BcLCB2 expression is detected by RT-PCR in all nonheading Chinese cabbage organs
Manually annotated by BRENDA team
LOCALIZATION
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
O15269, O15270
neuronal cytoplasm; neuronal cytoplasm
Manually annotated by BRENDA team
-
the Lcb1p and Lcb2p subunits of the SPT heterodimer may interact in the cytosol, as well as within the membrane and/or the lumen of the endoplasmic reticulum
Manually annotated by BRENDA team
-
in quiescent cells
Manually annotated by BRENDA team
Sphingomonas paucimobilis EY2395
-
-
-
Manually annotated by BRENDA team
-
the N-terminal is orientated to the lumenal side, the C-terminal is orienated to the cytosolic side
Manually annotated by BRENDA team
-
lumen, the Lcb1p and Lcb2p subunits of the SPT heterodimer may interact in the cytosol, as well as within the membrane and/or the lumen of the endoplasmic reticulum
Manually annotated by BRENDA team
O15269
SPT subunit 1 is present in the endoplasmic reticulum
Manually annotated by BRENDA team
-
the enzyme is a transmembrane protein
Manually annotated by BRENDA team
-
the Lcb1p and Lcb2p subunits of the SPT heterodimer may interact in the cytosol, as well as within the membrane and/or the lumen of the endoplasmic reticulum
Manually annotated by BRENDA team
Sphingomonas paucimobilis EY2395
-
bound
-
Manually annotated by BRENDA team
-
microsome isolation from mutant strains
-
Manually annotated by BRENDA team
-
membrane associated
-
Manually annotated by BRENDA team
O15269, O15270
recombinant from HEK 293 cells; recombinant from HEK 293 cells
-
Manually annotated by BRENDA team
-
nuclear association in proliferating cells
Manually annotated by BRENDA team
O15269
SPT subunit 1
Manually annotated by BRENDA team
A7BFV8, -
by immunoelectron microscopy it is shown that the protein is bound to the inner membrane of cells as peripheral membrane protein
-
Manually annotated by BRENDA team
A7BFV6, -
by immunoelectron microscopy it is shown that the protein is bound to the inner membrane of cells as peripheral membrane protein
-
Manually annotated by BRENDA team
A7BFV7, -
by immunoelectron microscopy it is shown that the protein is bound to the inner membrane of cells as peripheral membrane protein
-
Manually annotated by BRENDA team
additional information
O15269
in addition to its localization in the endoplasmic reticulum for de novo sphingolipid biosynthesis, subunit SPT1 is present in other cellular compartments, including focal adhesions where it is associated with cell morphology, immunofluorescent subcellular localization study, overview; SPT subunit 1, it binds to the focal adhesion protein vinculin
-
Manually annotated by BRENDA team
MOLECULAR WEIGHT
MOLECULAR WEIGHT MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
45000
-
A7BFV6, -
SDS-PAGE
45000
-
A7BFV7, -
SDS-PAGE
50000
-
A7BFV8, -
SDS-PAGE
90000
-
-
gel filtration
90000
-
A7BFV8, -
gel filtration
90000
-
A7BFV6, -
gel filtration
90000
-
A7BFV7, -
gel filtration
480000
-
-
holoenzyme, gel filtration; molecular mass of SPT complex determined by gel filtration
additional information
-
-
amino acid sequence determination
SUBUNITS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
?
-
x * 90000, SDS-PAGE
?
-
x * 65000, SDS-PAGE
dimer
-
2 * 44916, electrospray mass spectrometry; 2 * 50000, SDS-PAGE
dimer
-
2 * 45041, DNA sequence determination; 2 * 50000, SDS-PAGE
dimer
-
1 * Lcb1p + 1 * Lcb2p
dimer
Q9LSZ9
SPT is a heterodimer that consists of LCB1 and LCB2 subunits, which together form the active site of this enzyme
dimer
-
two SPT subunits, SPT1 and SPT2
dimer
Q6K8E7, Q9LSZ9
the enzyme is formed by two subunits, LCB1 and LCB2, i.e. long-chain base 1 and 2; the enzyme is formed by two subunits, LCB1 and LCB2, i.e. long-chain base 1 and 2
dimer
B2XR73
the enzyme is formed by two subunits, LCB1 and LCB2, i.e. long-chain base 1 and 2
dimer
-
2 * 42000, SDS-PAGE, gel filtration
dimer
Sphingomonas paucimobilis EY2395
-
2 * 44916, electrospray mass spectrometry; 2 * 50000, SDS-PAGE
-
heterodimer
-
subunits LCB1 and LCB2
heterodimer
-
structure comparison with the SPT from Sphingomonas paucimobilis, overview
heterotrimer
-
SPT is a heterodimer of 2 highly-related subunits, LCB1 and LCB2, existing in two isozyme forms LCB2a and LCB2b, associated with a third small activating subunit, either protein ssSPTa and protein ssSPTb, the proteins have a conserved hydrophobic central domain, reside in the membrane and interact with both hLCB1 and hLCB2 subunits, overview,protein ssSPTa and protein ssSPTb are required for maximal enzyme activity. SPT subunit interaction analysis, overview
homodimer
A7BFV8, -
gel filtration
homodimer
A7BFV6, -
gel filtration
homodimer
A7BFV7, -
gel filtration
homodimer
-
crystal structure
homodimer
Q93UV0
structure comparison with the human SPT, overview
homodimer
Sphingomonas paucimobilis EY2395
-
structure comparison with the human SPT, overview
-
octamer
-
results show that functional SPT is not a dimer, but a higher organized complex, composed of three distinct subunits (SPTLC1, SPTLC2 and SPTLC3) with a molecular mass of 480 kDa (gel filtration). The stoichiometry of SPTLC2 and SPTLC3 in this complex is not to be fixed and is changed dynamically in dependence of the tissue specific SPTLC2 and SPTLC3 expression levels. A model of an octameric SPT structure is proposed. By Blue-native-PAGE experiments it is shown that all three SPT subunits (SPTLC1-3) are co-localized within a single SPT complex
oligomer
-
the enzyme is composed of three different types of subunits, the stoichiometry of SPTLC2 and SPTLC3 in this complex seems not to be fixed and is probably changed dynamically in dependence of the tissue specific SPTLC2 and SPTLC3 expression levels, overview
oligomer
-
the enzyme is composed of three different types of subunits SPTLC1, SPTLC2, and SPTLC3
monomer
-
single-chain enzyme, domain structure, overview
additional information
-
Lcbp1 and Lcp2 are 2 subunits of the enzyme, tightly associated and not stable independently, tsc3 protein is loosely associated to them
additional information
-
lcb1 and lcb2 are 2 subunits, both necessary for enzyme activity, complexed in ratio 1:1
additional information
-
reconstitution of the holoenzyme from subunits SPTLC1 and SPLC2, isolated from placenta extract, and recombinant subunit SPTLC3 forming a single multisubunit SPT complex, overview
additional information
-
homology modelling of the R246G mutant SPT1
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
no glycoprotein
-
-
additional information
-
carrier lipid during extraction required for activity
Crystallization/COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
purified recombinant enzyme complexed with L-serine, sitting drop vapor diffusion method, 0.002 ml of protein solution containing 20 mg/ml SPT, 20 mM potasium phosphate, pH 7.7, and 10 mM pyridoxal 5'-phosphate, is mixed with 0.004 ml of reservoir solution containing 100 mM Tris-HCl; pH 8.5, 200 mM sodium acetate, 21.6% w/v PEG 4000, equilibration against 0.5 ml reservoir solution at 20C, 2 weeks, Schiff base formation between L-serine and pyridoxal 5'-phosphate in the crystal, X-ray diffraction structure determination and analysis at 2.3 A resolution, structural modelling
A7BFV6, -
after incubation with L-cycloserine
-
crystal structure of the holo-form of SPT is determined to 1.3 A resolution. Enzyme is a symmetrical homodimer with two active sites and a monomeric tertiary structure consisting of three domains. PLP cofactor is bound covalently to Lys265 as an internal aldimine/Schiff base and the active site is composed of residues from both subunits, located at the bottom of a deep cleft
-
purified His-tagged recombinant wild-type and mutant enzymes in complex with cofactor and substrates, wild-type enzyme from 10 mM Tris, pH 7.5, 150 mM NaCl, and 0.025 mM or 0.250 mM pyridoxal 5'-phosphate, different conditions for the mutants, overview. Mass spectroscopic structure analysis, overview
Q93UV0
pH 7.5, 30% PEG monomethylether 2000
-
pH STABILITY
pH STABILITY MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
6.8
8.5
A7BFV8, -
90% activity
6.8
8.5
A7BFV7, -
90% activity
additional information
-
A7BFV6, -
protein denatures below pH 7.2
TEMPERATURE STABILITY
TEMPERATURE STABILITY MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
37
-
-
30 min, stable
50
-
-
above, precipitation of enzyme
STORAGE STABILITY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
4C, Tris-HCl 20 mM, in sterile capped vials, 2 months without loss of activity
-
Purification/COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
purified as a water-soluble active homodimer
A7BFV8, -
-
Bacteroides melaninogenicus
-
of affinity-peptide tagged SPT complex
-
purified as water-soluble active homodimers
A7BFV6, -
recombinant SPT from Escherichia coli strain BL21(DE3)
A7BFV6, -
purified as a water-soluble active homodimer
A7BFV7, -
immobilized metal ion affinity chromatography (Ni2+), gel filtration
-
native and recombinant from E. coli, LCB1 and LCB2 co-immunoprecipitate
-
recombinant His-tagged wild-type and mutant enzymes from Escherichia coli strain BL21(DE3) by nickel affinity chromatography and gel filtration
Q93UV0
immobilized metal ion affinity chromatography
-
Cloned/COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
subunits LCB1 and LCB2 expression analysis; subunits LCB1 and LCB2 expression analysis
Q6K8E7, Q9LSZ9
subunits LCB1 and LCB2, phylogenetic tree, expression of Arabidopsis thaliana subunit LCB1 rescues the sphingolipid long-chain base auxotrophy of Saccharomyces cerevisiae SPT mutants when coexpressed with Arabidopsis thaliana LCB2
Q9LSZ9
expressed in Escherichia coli
A7BFV8, -
LCB2 cloning by ESTs, DNA and amino acid sequence determination and analysis, LCB2 expression analysis and phylogenetic analysis, overexpression of subunit LCB2 in Saccharomyces cerevisiae strain W303, transient overexpression in Nicotiana tabacum leaves via Agrobacterium tumefaciens strain GV2260-mediated transfection. BcLCB2 encodes a bona fide LCB2 subunit and the SPT activity in yeast results from co-expression of the BcLCB1 and BcLCB2 subunits
B2XR73
gene ehv050, DNA and amino acid sequence determination and analysis, functional expression of HA-tagged enzyme in Saccharmoyces cerevisiae endoplasmic reticulum, when the two subunits of the yeast SPT are thus expressed, the single-chain chimera is functional and displays a novel substrate preference, independently expressed domains of the viral SPT reassemble into an active protein, overview
-
expression of FLAG-tagged LCB1 in the deficient mutant LY-B, overproduction of LCB2 requires co-overproduction of LCB1
-
expression of HA-tagged C133W mutant SPTLC1 in CHO-K1 cells and in transgenic mice, the expression dominantly inhibits SPT activity
-
stable expression of LCB1 and R246G mutant SPT in enzyme-deficient hamster LY-B ovary cells restores SPT activity, DNA and amino acid sequence determination and analysis of the recombinantly expressed R246G mutant enzyme
-
; hLCB1 and hLCB2
-
expressed as a His-tagged fusion protein in Escherichia coli; individual overexpression of subunits SPTLC1, SPTLC2, and SPTLC3, fused to a C-terminal V5-his tag, in HEK-293 cells
-
expressed in HEK293T cells
O15269
expressed in yeast and mammalian cells, a triple fusion protein of the three subunits expressed in yeast and mammalian cells
-
expression in HEK 293 cells; expression in HEK 293 cells
O15269, O15270
overexpression of SPTLC3 in HEK-293 cells leads to the formation of two new sphingoid base metabolites, namely C16-sphinganine and C16-sphingosine. SPTLC3-expressing cells have higher in vitro SPT activities with lauryl- and myristoyl-CoA than SPTLC2-expressing cells, and SPTLC3 mRNA expression levels correlate closely with the C16-sphinganine synthesis rates in various human and murine cell lines. Quantitative reverse transcription--PCR analysis
-
overexpression of subunit SPTLC3 in HEK-293 cells, leading to an 2-3fold increased SPT activity, expression of subunit SPTLC3 in Hep-G2 cells and human trophoblast cells, quantitative expression analysis of SPTLC3
-
RT-PCR from mRNA of Molt-4 cells; RT-PCR from mRNA of Molt-4 cells
O15269, O15270
SPT1 and SPT2 real-time PCR expression analysis
-
ssSPTa and ssSPTb, DNA and amino acid sequence determination and analysis. Transient functional overexpression of ssSPTb-containing isozymes in CHO LyB cells increasing C20-long-chain bases. Expression of the human enzyme subunits in the lcb1DELTAlcb2DELTA double mutant Saccharomyces cerevisiae cells in various combinations constituting enzyme activity, overview. Expression in CHO LyB cells lacking endogenous SPT activity
-
subunit 2 expressed in HEK293 cells
O15270 AND Q9NUV7
expression of mLCB1 and LCB2 as glutathione-S-transferase fusion protein in Escherichia coli DH5alpha; in vitro transcription and translation of mLCB2; overexpression of mLCB1 and mLCB2 in human embryonic kidney cells, independently and in coexpression with mLCB1
-
subunit LCB1, DNA and amino acid sequence determination and analysis; subunit LCB2
B3Y000, B3Y9H2, -
genes LCB1 and LCB2, overexpression
-
expressed in Escherichia coli
A7BFV6, -
SPT expression in Escherichia coli strain BL21(DE3)
A7BFV6, -
expressed in Escherichia coli
A7BFV7, -
expressed in Escherichia coli
-
expression in Escherichia coli
-
His-tagged protein expressed in Escherichia coli BL21(DE3)
-
overexpression in Escherichia coli BL21 (DE3) pLysS, DNA sequence determination
-
recombinant expression of His-tagged wild-type and mutant enzymes in Escherichia coli strain BL21(DE3)
Q93UV0
His-tagged protein expressed in Escherichia coli BL21(DE3)
-
EXPRESSION
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
LCB2 is upregulated during hypersensitive cell death nduced by the Phytophthora boehmeriae elicitor PB90
B2XR73
lithospermic acid and two derivative esters, 9''-methyl lithospermate and 9'-methyl lithospermate,isolated from roots of Lithospermum erythrorhizon, significantly increase SPT expression in the relative quantity of SPT1 mRNA as well as SPT2 mRNA, by 21-59%, overview
-
Pseudomonas cichorii infection induces expression of subunit LCB2; Pseudomonas cichorii infection induces expression of subunit LCB2
B3Y000, B3Y9H2, -
short-term Mg deficiency results in an upregulation of major subunit 1 and 2 in cardiovascular tissues
-
ENGINEERING
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
R246G
-
naturally occuring mutation, comparison of de novo sphingolipid biosynthesis in wild-type LY-B cells and in LY-B cells expressing long-chain base subunit 1, LCB1, LC-ESI-MS/MS mass spectrometric analysis, overview
A352V
O15269
subunit 1, naturally occuring mutation, reduced activity in cells expressing mutant protein
C133V
-
reduced activity
C133W
O15269
subunit 1, naturally occuring mutation, reduced activity in cells expressing mutant protein
C133W
-
subunit 1, naturally occuring mutation, causing sensory neurophaty type 1, forms stable inactive heterodimers with subunit 2, forms heterotrimers with subunit 2 and subunit 3 with 10-20% of wild-type activity, heterotrimers expressed in yeast synthesize also C18-1-deoxyshinganine and expressed in mammalian cells synthesize also C18-1-deoxyshinganine and C20-1-deoxyshinganine, mutant heterotrimeric enzymes are active in yeast and mammalian cells and have an enhanced ability to condense alanine with acyl-CoA
C133Y
-
reduced activity
G382V
O15270 AND Q9NUV7
subunit 2, activity affected, naturally occuring mutation, hereditary sensory and autonomic neuropathy type I, expression in HEK293 cells increases concentration of neurotoxic 1-deoxysphinganine
S331F
O15269
subunit 1, naturally occuring mutation, reduced activity in cells expressing mutant protein, accumulation of 1-deoxysphingoid bases in HEK293T cells expressing mutant protein
V144D
-
reduced activity
DELTA2-9SPT
-
mutant bearing deleted residues from Ala2 to Pro9: Km values are not significantly changed compared to wild-type
H159A
-
site-directed mutagenesis, the mutant shows reduced activity and still forms the pyridoxal 5'-phosphate-L-serine-aldimine reaction intermediate
H159F
-
mutant enzyme shows no activity
H159F
-
site-directed mutagenesis, inactive mutant
H159W
-
site-directed mutagenesis, inactive mutant
H159Y
-
site-directed mutagenesis, inactive mutant
N100C
Q93UV0
site-directed mutagenesis, the mutation mimics the wild-type human enzyme and is fully active, crystal structure analysis
N100W
Q93UV0
site-directed mutagenesis, the mutation mimics the mutation in the human enzyme causing hereditary sensory autonomic neuropathy type 1, the mutant shows reduced activity compared to the wild-type enzyme. The mutation affects the chemistry of the pyridoxal 5'-phosphate, crystal structure analysis
N100Y
Q93UV0
site-directed mutagenesis, N100Y is less able to stabilize a quinonoid intermediate, the mutation mimics the mutation in the human enzyme causing hereditary sensory autonomic neuropathy type 1, the mutant shows reduced activity compared to the wild-type enzyme. The mutation affects the chemistry of the pyridoxal 5'-phosphate. The L-Ser external aldimine structure N100Y reveals significant differences that hinder the movement of a catalytically important Arg378 residue into the active site, crystal structure analysis
R378A
Q93UV0
site-directed mutagenesis, crystal structure analysis, the mutant is less able to stabilize a quinonoid intermediate
R378N
Q93UV0
site-directed mutagenesis, crystal structure analysis
R378N
-
residue highly mobile, activty 40fold reduced
N100C
Sphingomonas paucimobilis EY2395
-
site-directed mutagenesis, the mutation mimics the wild-type human enzyme and is fully active, crystal structure analysis
-
N100W
Sphingomonas paucimobilis EY2395
-
site-directed mutagenesis, the mutation mimics the mutation in the human enzyme causing hereditary sensory autonomic neuropathy type 1, the mutant shows reduced activity compared to the wild-type enzyme. The mutation affects the chemistry of the pyridoxal 5'-phosphate, crystal structure analysis
-
N100Y
Sphingomonas paucimobilis EY2395
-
site-directed mutagenesis, N100Y is less able to stabilize a quinonoid intermediate, the mutation mimics the mutation in the human enzyme causing hereditary sensory autonomic neuropathy type 1, the mutant shows reduced activity compared to the wild-type enzyme. The mutation affects the chemistry of the pyridoxal 5'-phosphate. The L-Ser external aldimine structure N100Y reveals significant differences that hinder the movement of a catalytically important Arg378 residue into the active site, crystal structure analysis
-
R378A
Sphingomonas paucimobilis EY2395
-
site-directed mutagenesis, crystal structure analysis, the mutant is less able to stabilize a quinonoid intermediate
-
R378N
Sphingomonas paucimobilis EY2395
-
site-directed mutagenesis, crystal structure analysis
-
R370A
-
strictly conserved in all prokaryotic enzymes and the Icb2 subunit of eukaryotic enzymes, no catalytic activity
R370K
-
strictly conserved in all prokaryotic enzymes and the Icb2 subunit of eukaryotic enzymes, 3% catalytic activity of wild type enzyme
additional information
Q9LSZ9
homozygous T-DNA insertion mutants for At LCB1 are not recoverable, but viability is restored by complementation with the wild-type At LCB1 gene, T-DNA disruption of AtLCB1 results in embryo lethality, partial RNAi suppression of At LCB1 expression is accompanied by a marked reduction in plant size that resulted primarily from reduced cell expansion, while the sphingolipid content remains unaltered, overview
additional information
-
the identification of the fumonisin B1 resistant11-2 (fbr11-2) mutant, an allele of lcb1-1, is reported. The fbr11-2 mutation, is transmitted only through female gametophytes and causes the formation of abortive microspores. During the second pollen mitosis, fbr11-2 initiates apoptotic cell death in binucleated microspores characteristic of nuclear DNA fragmentation, followed by cytoplasm shrinkage and organelle degeneration at the trinucleated stage. A double mutant with T-DNA insertions in two homologous LCB2 genes show a phenotype similar to fbr11-2
K311E
B2XR73
construction of mutant BcLCB2DELTAK311E that shows reduced activity compared to the wild-type enzyme
additional information
B2XR73
construction of an inactive pyridoxal 5'-phosphate binding site deletion mutant BcLCB2DELTA307-314. Overexpression of BcLCB2 in Nicotiana tabacum cv. Xanthi leaves suppresses the hypersensitive cell death initiated by elicitors and PB90-triggered H2O2 accumulation, while NbLCB2 silencing in Nicotiana benthamiana enhances elicitor-triggered hypersensitive cell death. BcLCB2 overexpression suppresses Bax- and oxidant stress-triggered yeast cell death. Reactive oxygen species accumulation induced by Bax is compromised in BcLCB2-overexpressing Saccharomyces cerevisiae strain W303 cells, detailed overview
C133W
-
site-directed mutagenesis, mutation of subunit SPTLC1, construction of transgenic mouse lines that ubiquitously overexpress either wild-type SPTLC1WT or mutant SPTLC1C133W in brain and liver microsomes, SPTLC1C133W mice develop age-dependent weight loss and mild sensory and motor impairments, fed SPTLC1C133W mice lose large myelinated axons in the ventral root of the spinal cord and demonstrate myelin thinning, there is also a loss of large myelinated axons in the dorsal roots, although the unmyelinated fibers are preserved, in the dorsal root ganglia, IB4 staining is diminished, whereas expression of the injury-induced transcription factor ATF3 is increased, phenotype, detailed overview
additional information
-
deficient mutant strain LY-B lacks LCB1 and has reduced content in LCB2, the latter is restored upon recombinant expression of LCB2
I504F
O15270 AND Q9NUV7
subunit 2, activity affected, naturally occuring mutation, hereditary sensory and autonomic neuropathy type I, expression in HEK293 cells increases concentration of neurotoxic 1-deoxysphinganine
additional information
-
mutations in the enzyme subunit SPTLC1 cause hereditary sensory and autonomic neuropathy type I, HSAN1, an adult onset, autosomal dominant neuropathy, HSAN1 patients have reduced SPT activity
additional information
O15269
elimination of subunit SPT1 activity using SPTLC1 siRNA in HEK-293 cells causes cell rounding
V359M
O15270 AND Q9NUV7
subunit 2, activity affected, naturally occuring mutation, hereditary sensory and autonomic neuropathy type I, expression in HEK293 cells increases concentration of neurotoxic 1-deoxysphinganine
additional information
B3Y000, B3Y9H2, -
reduced sphingolipid synthesis resulting from suppression of NbLCB2 expression interferes with normal leaf morphogenesis. NbLCB2 overexpression causes a cell death phenotype in Nicotiana benthamiana leaves. Downregulation of the genes encoding for the enzyme subunits compromises pathogen resistance against Pseudomonas cichorii; the phenotype of NbLCB1-silenced plants is almost the same as the control except for a slight downward curling of leaf edges in NbLCB1-silenced plants. Downregulation of the genes encoding for the enzyme subunits compromises pathogen resistance against Pseudomonas cichorii
additional information
-
SPT subunit LCB1 knockdown in L6 muscle cells by shRNA causes enzyme activity reduction by over 70%, silencing of LCB1 also leads to an attendant reduction in the expression of LCB2
additional information
-
natural mutant strains: SCS1/LCB2 knock-out mutant, scs1-1 mutant shows reduced activity, scs1-2 mutant is temperature-sensitive, but shows normal enzyme activity
additional information
-
tsc3 mutants show reduced enzyme activity, tsc3 is not required for expression, stability and membrane association of Lcb1p and Lcbp2
Renatured/COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
reconstitution of the holoenzyme from subunits SPTLC1 and SPLC2, isolated from placenta extract, and recombinant subunit SPTLC3 forming a single multisubunit SPT complex, overview
-
APPLICATION
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
molecular biology
-
results show that SPT modulated programmed cell death plays an important role in the regulation of male gametophyte development of Arabidopsis thaliana
medicine
-
decreased expression of SPT protein is one of the important causative factors for decreased ceramide levels in psoriasis
medicine
-
results show that the inhibition of atherosclerosis by the serine palmitoyltransferase inhibitor myriocin in apolipoprotein-E gene knockout mice is associated with reduced plasma glycosphingolipid and plasma sphingomyelin concentration; the SPT inhibitor myriocin induces the regression of atherosclerotic plaques in hyperlipidemic ApoE-deficient mice
medicine
-
results suggest that SPT activity might contribute to neuronal injury after kainate excitotoxicity in the rat hippocampus
analysis
-
useful as a model to elucidate the reaction mechanism
analysis
Sphingomonas paucimobilis EY2395
-
useful as a model to elucidate the reaction mechanism
-