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Enzyme Nomenclature
Information on EC 2.3.1.50 - serine C-palmitoyltransferase
for references in articles please use BRENDA:EC2.3.1.50
Word Map on EC 2.3.1.50
- 2.3.1.50
-
sphingolipids
- ceramide
- sphingomyelin
- myriocin
- sphingosine
-
sphingoid
-
sphingomyelinase
- neuropathy
-
long-chain
- fumonisins
-
sptlc1
- l-cycloserine
- glucosylceramide
- 3-ketodihydrosphingosine
- corneum
-
glycosphingolipids
- dihydrosphingosine
- sphingosine-1-phosphate
- dihydroceramide
-
plp-dependent
- beta-chloroalanine
- asmase
-
palmitate-induced
-
phosphorylceramide
- molecular biology
- medicine
-
aldimine
- paucimobilis
-
ceramide-induced
- c16-ceramide
-
14cserine
-
transepidermal
- analysis
- phytosphingosine
- sphingomonas
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The enzyme appears in viruses and cellular organisms
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EC NUMBER 
COMMENTARY 
2.3.1.50
-
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RECOMMENDED NAME
GeneOntology No.
serine C-palmitoyltransferase
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REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
palmitoyl-CoA + L-serine = CoA + 3-dehydro-D-sphinganine + CO2
mechanism
-
palmitoyl-CoA + L-serine = CoA + 3-dehydro-D-sphinganine + CO2
ordered bi-bi mechanism
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palmitoyl-CoA + L-serine = CoA + 3-dehydro-D-sphinganine + CO2
mechanism
-
palmitoyl-CoA + L-serine = CoA + 3-dehydro-D-sphinganine + CO2
formation of the external aldimine intermediate
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palmitoyl-CoA + L-serine = CoA + 3-dehydro-D-sphinganine + CO2
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
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palmitoyl-CoA + L-serine = CoA + 3-dehydro-D-sphinganine + CO2
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 Ca–H bond perpendicular to the pyridoxal 5'-phosphate-Schiff base plane, reaction mechanism with substrate synergism in the SPT reaction, overview. Modelling of reaction intermediates
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palmitoyl-CoA + L-serine = CoA + 3-dehydro-D-sphinganine + CO2
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 Dunathan’s 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
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palmitoyl-CoA + L-serine = CoA + 3-dehydro-D-sphinganine + CO2
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
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palmitoyl-CoA + L-serine = CoA + 3-dehydro-D-sphinganine + CO2
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
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palmitoyl-CoA + L-serine = CoA + 3-dehydro-D-sphinganine + CO2
the reaction proceeds via a key carbanion/quinonoid species and an internal aldimine/PLP-bound form of the enzyme
palmitoyl-CoA + L-serine = CoA + 3-dehydro-D-sphinganine + CO2
the reaction proceeds via a key carbanion/quinonoid species and an internal aldimine/PLP-bound form of the enzyme
-
palmitoyl-CoA + L-serine = CoA + 3-dehydro-D-sphinganine + CO2
the reaction proceeds via several intermediate states, the pyridoxal 5'-phosphate cofactor binds to an active site lysine residue as an internal aldimine/Schiff’s base (I). The L-serine displaces the lysine residue (Lys265) to form the PLP-L-serine external aldimine (II). Deprotonation of II gives a carbanion/quinonoid species (III) which condenses in a Claisen-like manner with the acyl-CoA thioester substrate to form a PLP-beta-keto acid, which then decarboxylates to generate the PLP-KDS product quinonoid (IV). This then reprotonates to form PLP-KDS aldimine (V) which is finally displaced by Lys265. The step releasing CoA and CO2 and producing the quinonoid intermediate species is irreversible. Interaction between the hydroxyl group of the L-serine substrate and the 5'-phosphate group of pyridoxal 5'-phosphate occurs in the formation of the external aldimine II, overview
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palmitoyl-CoA + L-serine = CoA + 3-dehydro-D-sphinganine + CO2
pyridoxal 5'-phosphate dependent reaction mechanism, key active site residues are His159, Asp231, His234, and Lys265
-
palmitoyl-CoA + L-serine = CoA + 3-dehydro-D-sphinganine + CO2
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 Ca–H bond perpendicular to the pyridoxal 5'-phosphate-Schiff base plane, reaction mechanism with substrate synergism in the SPT reaction, overview. Modelling of reaction intermediates
-
-
palmitoyl-CoA + L-serine = CoA + 3-dehydro-D-sphinganine + CO2
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
-
-
palmitoyl-CoA + L-serine = CoA + 3-dehydro-D-sphinganine + CO2
-
-
-
-
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REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Acyl group transfer
-
-
-
-
condensation
decarboxylation
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-
-
-
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PATHWAY
BRENDA Link
KEGG Link
MetaCyc Link
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SYSTEMATIC NAME
IUBMB Comments
palmitoyl-CoA:L-serine C-palmitoyltransferase (decarboxylating)
A pyridoxal-phosphate protein.
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CAS REGISTRY NUMBER
COMMENTARY
62213-50-7
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ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
infects the globally important marine calcifying microalga Emiliania huxleyi, gene ehv050
-
-
genetically corrected revertant strain LY-B/cLCB1 of deficient mutant LY-B; mutant defective strain LY-B
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two subunits of SPT, Sptlc1 and Sptlc2, i.e. LCB1 and LCB2 or SPT1 and SPT2
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487159, 487173, 487174, 657659, 659621, 671900, 673939, 674711, 688211, 704496, 704998, 719871, 736411
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subunits SPTLC1 (O15269) and SPTLC2(O15270); subunits SPTLC1 and SPTLC2
UniProt
subunit LCB1 fragment; two genes encoding the LCB2 and LCB1 subunits of the enzyme
B3Y9H2
UniProt
subunit LCB2; two genes encoding the LCB2 and LCB1 subunits of the enzyme
UniProt
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-
-
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GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
evolution
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the enzyme belongs to the PLP-superfamily and a member of the alpha-oxoamine synthase family (AOS, fold type I)
malfunction
metabolism
physiological function
additional information
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
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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
mutations in the SPTLC1 subunit associated with hereditary sensory and autonomic neuropathy type I
malfunction
mutations in both subunits hLCB1 (e.g., C133W and C133Y) and hLCB2a (e.g., V359M, G382V, and I504F) are identified in patients with hereditary sensory and autonomic neuropathy type I (HSAN1), an inherited disorder that affects sensory and autonomic neurons. These mutations result in substrate promiscuity, leading to formation of neurotoxic deoxysphingolipids found in affected individuals. Structure homology modeling to understand the impact of the hLCB2a mutations on the mechanism of the enzyme using the structure data from the Sphingomonas paucimobilis enzyme
malfunction
knockdown of small subunit of serine palmitoyltransferase a decreases the an lysophosphatidylinositol acyltransferase 1-dependent incorporation of exogenous aracidonic acid into phosphatidylinositol but does not affect the in vitro enzyme activity of an lysophosphatidylinositol acyltransferase 1 in the microsomal fraction. ssSPTa knockdown decreases the protein level of LPIAT1 in the crude mitochondrial fraction but not in total homogenate or the microsomal fraction
malfunction
hereditary sensory and autonomic neuropathy type 1 (HSAN1) is a rare autosomal dominant inherited peripheral neuropathy caused by mutations in the SPTLC1 and SPTLC2 subunits of serine palmitoyltransferase. The mutations induce a permanent shift in the substrate preference from L-serine to L-alanine, which results in the pathological formation of atypical and neurotoxic 1-deoxy-sphingolipids. Overview of clinical features of HSAN1 patients with SPTLC1 mutations, genotype-phenotype association in HSAN1
malfunction
myeloid cell-specific serine palmitoyltransferase subunit 2 haploinsufficiency reduces murine atherosclerosis. SPT subunit 2-haploinsufficient (Sptlc2+/-) macrophages have significantly lower SM levels in plasma membrane and lipid rafts. This reduction not only impairs inflammatory responses triggered by TLR4 and its downstream NF-kappaB and MAPK pathways, but also enhances reverse cholesterol transport mediated by ABC transporters. LDL receptor-deficient (Ldlr-/-) mice transplanted with Sptlc2+/- bone marrow cells exhibit significantly fewer atherosclerotic lesions after high-fat and high-cholesterol diet feeding. Additionally, Ldlr-/- mice with myeloid cell-specific Sptlc2 haploinsufficiency exhibit significantly less atherosclerosis than controls. Sptlc2 haploinsufficiency in macrophages leads to significant reductions of SM, glucosylceramide, and GM3 in macrophage plasma membranes and lipid rafts, resulting in altered raft distribution. Detailed phenotype overview
malfunction
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inhibiting the enzyme in the astrocytes decreases the levels of both TNFalpha and interleukin-1beta in the conditioned media, which in turn reduced the neural and acidic sphingomyelinase activities and BACE1 level in primary neurons, overview
malfunction
the S384D but not the S384E mutation is associated with increased 1-deoxysphingolipids formation
malfunction
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homozygous ssSPTa T-DNA mutants are not recoverable, and 50% nonviable pollen is detected in heterozygous ssSpta mutants. Pollen viability is recovered by expression of wild-type ssSPTa or ssSPTb under control of the ssSPTa promoter, indicating ssSPTa and ssSPTb functional redundancy. SPT activity and sensitivity to the PCD-inducing mycotoxin fumonisin B1 are increased by ssSPTa overexpression. Conversely, SPT activity and mycotoxin fumonisin B1 sensitivity are reduced in ssSPTa RNA interference lines
malfunction
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both short and prolonged time of inhibition of the enzyme by myriocin is sufficient to prevent ceramide accumulation and simultaneously reverse palmitate induced inhibition of insulin-stimulated glucose transport
malfunction
-
inhibiting the enzyme in the astrocytes decreases the levels of both TNFalpha and interleukin-1beta in the conditioned media, which in turn reduced the neural and acidic sphingomyelinase activities and BACE1 level in primary neurons, overview
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metabolism
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SPT is the key regulator enzyme in the ceramide de novo biosynthesis pathway
metabolism
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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
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SPT catalyzes the first and rate-limiting step of the sphingolipid biosynthetic pathway
metabolism
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SPT catalyzes the first and rate-limiting step of the sphingolipid biosynthetic pathway
metabolism
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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
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SPT catalyzes the first and rate-limiting step in the de novo synthesis of sphingolipids
metabolism
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SPT catalyzes the first committed step in sphingolipid biosynthesis
metabolism
the enzyme catalyses the first step of de novo sphingolipid biosynthesis
metabolism
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the enzyme catalyses the first step of de novo sphingolipid biosynthesis
metabolism
the small subunit of serine palmitoyltransferase a (ssSPTa) as an lysophosphatidylinositol acyltransferase 1 (LPIAT1)-interacting protein and colocalizes with LPIAT1 in cultured mammalian cells
metabolism
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sphingolipids are essential components of cellular membranes formed from the condensation of L-serine and a long-chain acyl thioester. This first step is catalyzed by the pyridoxal 5'-phosphate-dependent enzyme serine palmitoyltransferase
metabolism
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eukaryotic serine palmitoyltransferase is an integral endoplasmic reticulum membrane protein that contains a head-to-tail heterodimer of two related but distinct subunits, LCB1 and LCB2, with a single catalytic site. There are additional subunits necessary for maximal activity as well as associated negative regulatory components
metabolism
serine palmitoyltransferase long chain-1 (SPTLC1) is the first enzyme of sphingolipid biosynthesis
metabolism
serine palmitoyltransferase is the first and rate-limiting enzyme of the de novo biosynthetic pathway of sphingomyelin. Both serine palmitoyltransferase and sphingomyelin are implicated in the pathogenesis of atherosclerosis, the development of which is driven by macrophages
metabolism
several mutations in SPT are associated with the hereditary sensory and autonomic neuropathy type I, HSAN1. Wild-type SPT forms 1-deoxysphingolipids under certain conditions, and elevated levels are found in individuals with the metabolic syndrome and diabetes
metabolism
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serine palmitoyltransferase, composed of LCB1 and LCB2 subunits, catalyzes the primary regulatory point for sphingolipid synthesis
metabolism
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the first and rate-limiting step of de novo synthesis is the condensation of a fatty acyl-CoA, usually palmitoyl-CoA, with serine, which is catalyzed by the enzyme serine palmitoyltransferase to form 3-dehydrosphinganin
metabolism
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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
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physiological function
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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
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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
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
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
physiological function
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the enzyme is required for de novo sphingolipid biosynthesis
physiological function
the small subunit of serine palmitoyltransferase a (ssSPTa) plays a role in fatty acid remodeling of phosphatidyl inositol, probably by facilitating the MAM localization oflysophosphatidylinositol acyltransferase 1, LPIAT1
physiological function
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the role of the small activating subunits of serine palmitoyltransferase, ssSPTs, is to increase SPT activity without compromising substrate specificity
physiological function
phosphorylation of serine palmitoyltransferase long chain-1 (SPTLC1) on tyrosine 164 by the fusion kinase BCR-ABL inhibits the SPTLC1 enzyme activity. Inhibition of BCR-ABL kinase using either imatinib or shRNA-mediated silencing leads to the activation of SPTLC1 and to increased apoptosis in both K562 and LAMA-84 cells, a mechanistic explanation for imatinib-mediated cell death
physiological function
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serine palmitoyltransferase in the astrocytes increases ceramide levels, which enhances the release of cytokines that mediate the activation of neural and acidic sphingomyelinase (N-SMase and A-SMase) in the neurons, to propagate the deleterious effects of palmitate, i.e. BACE1 upregulation and amyloidogenesis in primary rat neurons, overview
physiological function
specificity of wild-type SPT might by dynamically regulated by a phosphorylation at position S384
physiological function
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enzyme activators, the small subunits are essential for male gametophytes, are important for mycotoxin fumonisin B1 sensitivity, and limit sphingolipid synthesis in planta
physiological function
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serine palmitoyltransferase in the astrocytes increases ceramide levels, which enhances the release of cytokines that mediate the activation of neural and acidic sphingomyelinase (N-SMase and A-SMase) in the neurons, to propagate the deleterious effects of palmitate, i.e. BACE1 upregulation and amyloidogenesis in primary rat neurons, overview
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additional information
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the interaction between the hydroxyl group of the L-serine substrate and the 5'-phosphate group of pyridoxal 5'-phosphate is important for substrate specificity and optimal catalytic efficiency. Structure of the PLP-L-serine external aldimine intermediate of the enzyme, PDB ID 2W8J, overview
additional information
wild-type and mutant enzyme structure homology modeling and structure-function analyses, overview
additional information
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key active site residues are His159, Asp231, His234, and Lys265
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SUBSTRATE
PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
arachidoyl-CoA + L-serine
CoA + 2-amino-1-hydroxydocosan-3-one + CO2
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37% activity compared to that with palmitoyl-CoA
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?
elaidoyl-CoA + L-serine
CoA + 2-amino-1-hydroxy-trans-11-eicosen-3-one + CO2
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39% activity compared to that with palmitoyl-CoA
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-
?
L-serine + stearoyl-CoA
CoA + (2S)-2-amino-1-hydroxyicosan-3-one + CO2
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-
-
-
?
lauroyl-CoA + L-serine
CoA + 2-amino-1-hydroxytetradecan-3-one + CO2
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18% activity compared to that with palmitoyl-CoA
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-
?
myristoleoyl-CoA + L-serine
CoA + 2-amino-1-hydroxy-cis-11-hexadecen-3-one + CO2
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46% activity compared to that with palmitoyl-CoA
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-
?
oleoyl-CoA + L-serine
CoA + 2-amino-1-hydroxy-11-cis-eicosen-3-one + CO2
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57% activity compared to that with palmitoyl-CoA
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-
?
palmitoyl-CoA + L-serine
3-dehydrosphinganine + CoA + CO2
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-
-
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?
stearoyl-CoA + L-serine
(2S)-2-amino-1-hydroxyicosan-3-one + CoA + CO2
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-
-
-
?
stearoyl-CoA + L-serine
CoA + (2S)-2-amino-1-hydroxyicosan-3-one + CO2
-
-
-
-
?
stearoyl-CoA + L-serine
CoA + 2-amino-1-hydroxyeicosan-3-one + CO2
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51% activity compared to that with palmitoyl-CoA
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-
?
L-serine + palmitoyl-CoA
CoA + 3-dehydro-D-sphinganine + CO2
-
-
-
?
L-serine + palmitoyl-CoA
CoA + 3-dehydro-D-sphinganine + CO2
-
-
-
-
?
myristoyl-CoA + L-serine
CoA + 2-amino-1-hydroxy-cis-11-hexadecen-3-one + CO2
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SPT is the first and rate-limiting enzyme of sphingolipid biosynthesis
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-
?
myristoyl-CoA + L-serine
CoA + 2-amino-1-hydroxy-cis-11-hexadecen-3-one + CO2
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the viral enzyme exhibits preference for myristoyl-CoA rather than palmitoyl-CoA
-
-
?
myristoyl-CoA + L-serine
CoA + 2-amino-1-hydroxyhexadecan-3-one + CO2
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75% activity compared to that with palmitoyl-CoA
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-
?
myristoyl-CoA + L-serine
CoA + 2-amino-1-hydroxyhexadecan-3-one + CO2
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75% activity compared to that with palmitoyl-CoA
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-
?
myristoyl-CoA + L-serine
CoA + ? + CO2
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recombinant SPTLC3 subunit in HEK-293 cells
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-
?
n-heptadecanoyl-CoA + L-serine
CoA + 2-amino-1-hydroxynonadecan-3-one + CO2
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75% activity compared to that with palmitoyl-CoA
-
-
?
n-heptadecanoyl-CoA + L-serine
CoA + 2-amino-1-hydroxynonadecan-3-one + CO2
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75% activity compared to that with palmitoyl-CoA
-
-
?
palmitoleoyl-CoA + L-serine
CoA + 2-amino-1-hydroxy-cis-11-octadecen-3-one + CO2
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80% activity compared to that with palmitoyl-CoA
-
-
?
palmitoleoyl-CoA + L-serine
CoA + 2-amino-1-hydroxy-cis-11-octadecen-3-one + CO2
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80% activity compared to that with palmitoyl-CoA
-
-
?
palmitoyl-CoA + L-alanine
CoA + (2S)-2-aminooctadecan-3-one + CO2
wild-type enzyme can metabolize L-alanine under certain conditions
-
-
?
palmitoyl-CoA + L-alanine
CoA + (2S)-2-aminooctadecan-3-one + CO2
low activity with the wild-type enzyme, but increased activity with some mutants of the enzyme, overview
-
-
?
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
-
-
-
?
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
step in the sphingolipid biosynthetic pathway, overview
-
-
?
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
-
-
-
?
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
-
-
-
?
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
-
SPT is the first and rate-limiting enzyme of sphingolipid biosynthesis
-
-
?
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
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the viral enzyme exhibits preference for myristoyl-CoA rather than palmitoyl-CoA
-
-
?
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
-
-
-
-
?
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
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first step of biosynthesis of sphingolipid bases
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-
?
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
-
key enzyme of sphingolipid metabolism
-
-
?
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
-
the enzyme catalyses the rate limiting step for the de novo synthesis of sphingolipids
-
-
?
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
-
palmitoyl-CoA is the preferred substrate
-
ir
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
-
optimal palmitoyl-CoA concentration is 0.2 mM
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ir
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
-
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
-
-
-
-
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
-
-
-
-
?
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
-
-
-
-
?
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
-
-
-
ir
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
-
-
-
?
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
-
palmitoyl-CoA is used in preference to other saturated or unsaturated acyl-CoA substrates
-
-
?
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
-
involved in cellular stress response
-
-
?
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
first step of biosynthesis of sphingolipid bases
-
-
-
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
-
first step of biosynthesis of sphingolipid bases
-
?
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
-
first step of biosynthesis of sphingolipid bases
-
-
?
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
rate-limiting enzyme in synthesis of sphingolipids
-
-
-
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
-
rate-limiting enzyme in synthesis of sphingolipids
-
?
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
-
rate-limiting enzyme in synthesis of sphingolipids
-
-
?
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
initial step of de novo ceramide biosynthesis
-
-
-
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
-
initial step of de novo ceramide biosynthesis
-
-
?
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
-
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
-
the enzyme catalyses the rate limiting step for the de novo synthesis of sphingolipids
-
-
?
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
-
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
-
first and rate-limiting step in the de novo synthesis of sphingolipids
-
-
?
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
-
first step of biosynthesis of sphingolipid bases
-
?
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
-
first step of biosynthesis of sphingolipid bases
-
-
?
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
-
key enzyme in ceramide synthesis, overview
-
-
?
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
-
-
-
-
-
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
-
-
-
-
ir
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
-
initial step of de novo ceramide biosynthesis
-
ir
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
-
-
-
-
?
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
-
-
i.e. 2-amino-1-hydroxyoctadecane-3-one, i.e. 3-oxo-dihydroxysphingosine
ir
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
-
palmitoyl-CoA is the preferred substrate
-
-
?
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
-
palmitoyl-CoA is the preferred substrate
-
-
ir
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
-
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
-
no other amino acids can substitute for serine
-
-
ir
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
-
first step of biosynthesis of sphingolipid bases
-
-
-
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
-
first step of biosynthesis of sphingolipid bases
-
ir
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
-
initial step of de novo ceramide biosynthesis
-
ir
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
-
the enzyme catalyses the first step in the ceramide biosynthesis pathway
-
-
?
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
-
the enzyme is involved in the ceramide metabolism, overview
-
-
?
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
-
-
-
-
?
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
-
-
-
-
?
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
-
-
-
?
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
-
-
-
-
ir
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
-
-
-
ir
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
-
involved in cellular stress response
-
-
?
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
-
first step of biosynthesis of sphingolipid bases
-
-
?
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
-
rate-limiting enzyme in synthesis of sphingolipids
-
-
?
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
-
initial step of de novo ceramide biosynthesis
-
-
?
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
-
initial step of de novo ceramide biosynthesis
-
ir
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
-
-
-
?
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
-
-
-
-
?
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
-
-
-
?
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
-
-
-
?
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
-
-
-
-
?
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
-
-
?
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
-
-
-
-
?
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
-
palmitoyl-CoA is the preferred substrate
-
?
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
-
no other amino acids can substitute for serine
-
?
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
rate-limiting enzyme in synthesis of sphingolipids
-
?
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
-
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
-
interaction between the hydroxyl group of the L-serine substrate and the 5'-phosphate group of pyridoxal 5'-phosphate. This interaction is important for substrate specificity and optimal catalytic efficiency
-
-
?
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
-
palmitoyl-CoA is the preferred substrate
-
?
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
-
no other amino acids can substitute for serine
-
?
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
-
-
-
?
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
-
-
-
-
-
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
-
-
-
ir
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
-
-
-
-
ir
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
-
-
i.e. 2-amino-1-hydroxyoctadecane-3-one, i.e. 3-oxo-dihydroxysphingosine
ir
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
-
first step of biosynthesis of sphingolipid bases
-
ir
additional information
?
-
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
?
-
-
the viral single-chain enzyme might form multiprotein complexes in vivo with functions different from the monomer
-
-
-
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
?
-
-
the expression of two SPT isoforms could be a cellular mechanism to adjust SPT activity to tissue-specific requirements of sphingolipid synthesis
-
-
-
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
-
-
-
additional information
?
-
1-deoxysphingolipids are atypical sphingolipids that are formed by the enzyme serine palmitoyltransferase due to a promiscuous use of L-alanine over its canonical substrate L-serine. Wild-type SPT forms 1-deoxysphingolipids under certain conditions, and elevated levels are found in individuals with the metabolic syndrome and diabetes
-
-
-
additional information
?
-
the small subunit of serine palmitoyltransferase a (ssSPTa) as an lysophosphatidylinositol acyltransferase 1 (LPIAT1)-interacting protein
-
-
-
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
?
-
-
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
?
-
-
no activity with L-phosphoserine
-
-
-
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
NATURAL SUBSTRATES
NATURAL PRODUCTS
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
myristoyl-CoA + L-serine
CoA + 2-amino-1-hydroxy-cis-11-hexadecen-3-one + CO2
-
SPT is the first and rate-limiting enzyme of sphingolipid biosynthesis
-
-
?
myristoyl-CoA + L-serine
CoA + ? + CO2
-
recombinant SPTLC3 subunit in HEK-293 cells
-
-
?
palmitoyl-CoA + L-alanine
CoA + (2S)-2-aminooctadecan-3-one + CO2
O15270
wild-type enzyme can metabolize L-alanine under certain conditions
-
-
?
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
Q9LSZ9
step in the sphingolipid biosynthetic pathway, overview
-
-
?
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
E2RKV3
-
-
-
?
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
-
SPT is the first and rate-limiting enzyme of sphingolipid biosynthesis
-
-
?
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
-
first step of biosynthesis of sphingolipid bases
-
-
?
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
-
key enzyme of sphingolipid metabolism
-
-
?
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
-
the enzyme catalyses the rate limiting step for the de novo synthesis of sphingolipids
-
-
?
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
-
-
-
-
?
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
O15269, O15270
-
-
-
ir
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
O15269 and O15270
-
-
-
?
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
-
involved in cellular stress response
-
-
?
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
O15269, O15270
first step of biosynthesis of sphingolipid bases
-
-
-
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
-
first step of biosynthesis of sphingolipid bases
-
?
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
-
first step of biosynthesis of sphingolipid bases
-
-
?
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
O15269, O15270
rate-limiting enzyme in synthesis of sphingolipids
-
-
-
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
-
rate-limiting enzyme in synthesis of sphingolipids
-
?
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
-
rate-limiting enzyme in synthesis of sphingolipids
-
-
?
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
O15269, O15270
initial step of de novo ceramide biosynthesis
-
-
-
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
-
initial step of de novo ceramide biosynthesis
-
-
?
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
-
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
-
the enzyme catalyses the rate limiting step for the de novo synthesis of sphingolipids
-
-
?
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
-
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
-
first and rate-limiting step in the de novo synthesis of sphingolipids
-
-
?
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
-
first step of biosynthesis of sphingolipid bases
-
?
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
-
first step of biosynthesis of sphingolipid bases
-
-
?
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
-
key enzyme in ceramide synthesis, overview
-
-
?
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
-
initial step of de novo ceramide biosynthesis
-
ir
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
-
-
-
-
?
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
-
-
-
ir
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
-
first step of biosynthesis of sphingolipid bases
-
-
-
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
-
first step of biosynthesis of sphingolipid bases
-
ir
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
-
initial step of de novo ceramide biosynthesis
-
ir
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
-
the enzyme catalyses the first step in the ceramide biosynthesis pathway
-
-
?
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
-
the enzyme is involved in the ceramide metabolism, overview
-
-
?
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
-
-
-
-
?
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
-
-
-
-
?
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
-
-
-
ir
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
-
involved in cellular stress response
-
-
?
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
-
first step of biosynthesis of sphingolipid bases
-
-
?
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
-
rate-limiting enzyme in synthesis of sphingolipids
-
-
?
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
-
initial step of de novo ceramide biosynthesis
-
-
?
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
-
initial step of de novo ceramide biosynthesis
-
ir
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
-
-
-
-
?
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
A7BFV6
-
-
-
?
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
-
-
-
-
?
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
Q93UV0
rate-limiting enzyme in synthesis of sphingolipids
-
?
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
Q93UV0
-
-
-
?
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
-
-
-
ir
palmitoyl-CoA + L-serine
CoA + 3-dehydro-D-sphinganine + CO2
-
first step of biosynthesis of sphingolipid bases
-
ir
additional information
?
-
B5LED9
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
?
-
-
the viral single-chain enzyme might form multiprotein complexes in vivo with functions different from the monomer
-
-
-
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
?
-
-
the expression of two SPT isoforms could be a cellular mechanism to adjust SPT activity to tissue-specific requirements of sphingolipid synthesis
-
-
-
additional information
?
-
O15270
1-deoxysphingolipids are atypical sphingolipids that are formed by the enzyme serine palmitoyltransferase due to a promiscuous use of L-alanine over its canonical substrate L-serine. Wild-type SPT forms 1-deoxysphingolipids under certain conditions, and elevated levels are found in individuals with the metabolic syndrome and diabetes
-
-
-
additional information
?
-
Q969W0
the small subunit of serine palmitoyltransferase a (ssSPTa) as an lysophosphatidylinositol acyltransferase 1 (LPIAT1)-interacting protein
-
-
-
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
?
-
-
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
-
-
-
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
COFACTOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
pyridoxal 5'-phosphate
-
pyridoxal 5'-phosphate can be resolved from the enzyme by dialysis
pyridoxal 5'-phosphate
-
bound to epsilon-amino group of a lysine residue in the active site
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, 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
subunit LCB2 possesses a binding site
pyridoxal 5'-phosphate
dependent on, bound by lysine 265 residue on subunit LCB2a
pyridoxal 5'-phosphate
-
dependent on, bound by lysine 265 residue, interaction between the hydroxyl group of the L-serine substrate and the 5'-phosphate group of pyridoxal 5'-phosphate. This interaction is important for substrate specificity and optimal catalytic efficiency
pyridoxal 5'-phosphate
-
-
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Mn2+
additional information
-
NaCl, LiCl, MgCl2, MnCl2 have no effect on activity
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
INHIBITORS
ORGANISM
UNIPROT
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
4-amino-3-isoxazolidone
-
D-cycloserine and L-cycloserine are inhibitors, L-cycloserine is 14-fold more effective than D-cycloserine
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
mycotoxin fumonisin B1
-
enzyme sensitivity to the inhibitor is increased by small subunit ssSPTa overexpression
palmitoyl CoA
enzyme shows remarkable substrate inhibition at palmitoyl-CoA concentrations higher than 0.1 nM
thermozymocidin
-
i.e. ISP-1; strong inhibition, reversible by sphingosine
beta-chloro-L-alanine
-
rapid, irreversible and time dependent inhibition at the active site; stereospecific, no inhibition by beta-chloro-D-alanine; suicide substrate
myriocin
a potent inhibitor of SPT, that has no effect on Bax-induced programmed cell death
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
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
-
both short and prolonged time of inhibition of the enzyme by myriocin is sufficient to prevent ceramide accumulation and simultaneously reverse palmitate induced inhibition of insulin-stimulated glucose transport
myriocin
-
i.e. (2S,3R,4R,6E)-2-amino-3,4-dihydroxy-2-(hydroxymethyl)-14-oxo-6-eicosenoic acid, or thermozymocidin and ISP-1, is a fungal natural product, kinetics and molecular mechanism of enzyme inhibition, overview. Myriocin is a potent SPT enzyme inhibitor. It initially forms an external aldimine with pyridoxal 5'-phosphate at the active site, the structure of the resulting co-complex explains its nanomolar affinity for the enzyme. The cofactor-inhibitor co-complex, PLP-myriocin aldimine, catalytically degrades via an unexpected retro-aldol-like cleavage mechanism to a C18 aldehyde which in turn acts as a suicide inhibitor of the enzyme by covalent modification of the essential catalytic lysine. This dual mechanism of inhibition rationalizes the extraordinary potency and longevity of myriocin inhibition. Incubations of enzyme SPT with myriocin is consistent with the formation of an initial enzyme-inhibitor complex which is noncovalent in nature and reversible, albeit with a very slow off rate (koff), the PLP-myriocin aldimine as the initial competitive inhibitory species. In contrast, for the enzyme preincubated with myriocin for 16 h, no detectable regain in activity is observed after dialysis either at 3 or 24 h, the second formed covalent adduct acts as an irreversible inhibitor of enzyme SPT
additional information
-
recombinant expression of C133W mutant SPTLC1 in cell cultures dominantly inhibits the endogenous SPT activity
-
additional information
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
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
-
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
-
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ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
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
-
binds to the smSPT-external aldimine complex and enhances the exchange rate of the alpha-proton of L-serine by smSPT
small activating subunit of serine palmitoyltransferase
-
ssSPT, the small subunits of human serine palmitoyltransferase (hssSPTs) are glycoproteins and activate the catalytic hLCB1/hLCB2 heterodimer. Two isoforms exist, ssSPTa and ssSPTb, a single amino acid, residue 25, difference between ssSPTa and ssSPTb is responsible for the acyl-CoA preference of heterotrimers containing each isoform. the role of the small activating subunits of serine palmitoyltransferase, ssSPTs, is to increase SPT activity without compromising substrate specificity. Activity and acyl-CoA selectivity of the ssSPTs reside in the conserved core. Deletion of the N-terminal 10 amino acids of small activating subunit of serine palmitoyltransferase isoforms ssSPTa or ssSPTb has no effect on the ability of the proteins to activate hLCB1/hLCB2a heterodimers sufficiently to complement growth of yeast lacking endogenous serine palmitoyltransferase. The region responsible for the acyl-CoA selectivity of ssSPTa lays between residues Ser11 and Glu27, the acyl-CoA selectivity does not lie in the C-terminal region of ssSPTb, overview
-
etoposide
; 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
small subunits of serine palmitoyltransferase
-
isoforms ssSPTa and ssSPTb, UniProt A8MSB8 and F4IPU5, strongly stimulate SPT activity. Small subunit ssSPTa transcripts are more enriched in all organs and over 400fold more abundant in pollen than small subunit ssSPTb transcripts. Homozygous ssSPTa T-DNA mutants are not recoverable, and 50% nonviable pollen is detected in heterozygous ssspta mutants. The small subunits are essential for male gametophytes, are important for mycotoxin fumonisin B1 sensitivity, and limit sphingolipid synthesis in planta
-
small subunits of serine palmitoyltransferase
small subunits of SPT, ssSPTa and ssSPTb, increase human SPT activity by 50-100fold when coexpressed with enzyme subunits hLCB1 and hLCBa
-
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
-
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
-
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KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
9.6
L-alanine
-
C133W mutant protein, pH not specified in the publication, temperature not specified in the publication
0.0129
stearoyl-CoA
-
pH not specified in the publication, temperature not specified in the publication
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
1.4
L-serine
-
C133W mutant protein, pH not specified in the publication, temperature not specified in the publication
0.0234
palmitoyl-CoA
-
pH not specified in the publication, temperature not specified in the publication
0.031
palmitoyl-CoA
-
pH 7.5, 37°C, recombinant mutant N100Y; pH 7.5, 37°C, recombinant mutant R378N
0.0356
palmitoyl-CoA
-
recombinant wild-type enzyme, pH 7.5, 25°C
additional information
L-alanine
-
wild-type enzyme does not utilize alanine efficiently
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 of wild-type and mutant enzymes
-
additional information
additional information
-
Michaelis-Menten kinetics of wild-type and mutant enzymes
-
additional information
additional information
-
Michaelis-Menten kinetics.The regenerated enzyme displays similar Km and kcat values to the purified enzyme, with only a small increase in the Km for L-serine
-
additional information
additional information
-
Michaelis-Menten kinetics of wild-type and mutant enzyme
-
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TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.083
stearoyl-CoA
-
pH not specified in the publication, temperature not specified in the publication
0.0687
palmitoyl-CoA
-
pH not specified in the publication, temperature not specified in the publication
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kcat/KM VALUE [1/mMs-1]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
6.416
stearoyl-CoA
-
pH not specified in the publication, temperature not specified in the publication
0.0881
L-serine
-
pH not specified in the publication, temperature not specified in the publication
2.936
palmitoyl-CoA
-
pH not specified in the publication, temperature not specified in the publication
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Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
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
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IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.0000054
(2S,3R)-2-amino-12-hydroxy-2-hydroxymethyl-3-sulfooxy-octadecanoic acid
Cricetulus griseus;
-
IC50: 5.4 nM
0.00003
(2S,3R)-2-amino-12-[(Z)-hydroxyimino]-2-hydroxymethyl-3-sulfooxy-octadecanoic acid
Cricetulus griseus;
-
IC50: 30 nM
0.0000032
(2S,3R)-2-amino-3,12-dihydroxy-2-hydroxymethyl-octadecanoic acid
Cricetulus griseus;
-
IC50: 3.2 nM
0.0000035
(2S,3R)-2-amino-3-hydroxy-2-hydroxymethyl-12-oxo-octadecanoic acid
Cricetulus griseus;
-
IC50: 3.5 nM
0.000017
(2S,3R)-2-amino-3-hydroxy-2-hydroxymethyl-12-oxo-octadecanoic acid methyl ester
Cricetulus griseus;
-
IC50: 17 nM
0.000003
sulfamisterin
Cricetulus griseus;
-
antibiotic derived from Pycnidiella sp., IC50: 3 nM
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SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
0.000044
0.00011
-
substrate alanine, C133W mutant protein, pH not specified in the publication, temperature not specified in the publication
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
additional information
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
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pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
7.4
7.5
7.5 - 8
8.3
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pH RANGE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
7 - 8
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TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
25
37
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SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
-
the cell shows very low enzyme activity due to deficiency of subunit LCB1
-
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
except for ovarian epithelium; except for ovarian epithelium
-
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
-
small subunit ssSPTa transcripts are more enriched in all organs and over 400fold more abundant in pollen than small subunit ssSPTb transcripts
additional information
-
increased SPT enzyme activity in reactive astrocytes of the hippocampus at 2 weeks post-kainate injection
leukemia Molt-4 cells; leukemia Molt-4 cells; leukemia Molt-4 cells
young, expression of LCB1; young, expression of LCB2
-
elevation of ceramide in serum lipoproteins during acute phase response to inflammation is accompanied by activation of serine-palmitoyl transferase in liver
-
elevation of ceramide in serum lipoproteins during acute phase response to inflammation is accompanied by activation of serine-palmitoyl transferase in liver
mucosal from colon, lung, prostate, stomach, thyroid, uterus, vascular tissue; mucosal from colon, lung, prostate, stomach, thyroid, uterus, vascular tissue
additional information
ubiquitous expression of subunits LCB1 and LCB2 in the plant
additional information
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
additional information
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
additional information
BcLCB2 expression is detected by RT-PCR in all nonheading Chinese cabbage organs
additional information
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
additional information
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
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LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
additional information
-
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
-
the N-terminal is orientated to the lumenal side, the C-terminal is orienated to the cytosolic side
SPT subunit 1 is present in the endoplasmic reticulum
-
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
-
the enzyme is a transmembrane protein
-
the N-termini of the small activating subunit of serine palmitoyltransferase isoforms are locatedin the cytosol, their C-termini in the lumen, and they contain a single transmembrane domain
-
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
recombinant from HEK 293 cells; recombinant from HEK 293 cells
-
by immunoelectron microscopy it is shown that the protein is bound to the inner membrane of cells as peripheral membrane protein
-
-
by immunoelectron microscopy it is shown that the protein is bound to the inner membrane of cells as peripheral membrane protein
-
by immunoelectron microscopy it is shown that the protein is bound to the inner membrane of cells as peripheral membrane protein
-
additional information
-
ABL-mediated phosphorylation of enzyme SPTLC1 affects its endoplasmic reticulum localization
-
additional information
ABL-mediated phosphorylation of enzyme SPTLC1 affects its endoplasmic reticulum localization
-
additional information
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
-
additional information
ABL-mediated phosphorylation of enzyme SPTLC1 affects its endoplasmic reticulum localization
-
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PDB
SCOP
CATH
UNIPROT
ORGANISM
Sphingomonas paucimobilis;
A5VD79
Sphingomonas wittichii (strain RW1 / DSM 6014 / JCM 10273);
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MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
45000
50000
90000
480000
-
holoenzyme, gel filtration; molecular mass of SPT complex determined by gel filtration
90000
-
about, recombinant wild-type enzyme and mutants V246M and G385F, gel filtration
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SUBUNITS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
dimer
heterodimer
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
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
additional information
dimer
SPT is a heterodimer that consists of LCB1 and LCB2 subunits, which together form the active site of this enzyme
dimer
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
the enzyme is formed by two subunits, LCB1 and LCB2, i.e. long-chain base 1 and 2
dimer
-
2 * 44916, electrospray mass spectrometry; 2 * 50000, SDS-PAGE
dimer
-
2 * 44916, electrospray mass spectrometry; 2 * 50000, SDS-PAGE
-
heterodimer
-
serine palmitoyltransferase is composed of LCB1 and LCB2 subunits
heterodimer
-
structure comparison with the SPT from Sphingomonas paucimobilis, overview
heterodimer
the membrane-bound heterodimer composed of two subunits hLCB1 and hLCB2a/b. The hLCB1 and hLCB2 subunits display relatively high sequence homology to each other, but only the hLCB2a subunit contains key catalytic residues including the lysine that binds pyridoxal 5'-phosphate. Subunit hLCB1 lacks these residues but contains other residues involved in catalysis,the hLCB1/hLCB2a heterodimer has a single active site
heterodimer
the membrane-bound heterodimer composed of two subunits SPTLC1 and SPTLC2
heterodimer
-
the membrane-bound heterodimer composed of two subunits hLCB1 and hLCB2a/b
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
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
-
the small activating subunits of serine palmitoyltransferase, ssSPTs, are glycoproteins and are part of the enzyme complex
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
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POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
glycoprotein
-
the small activating subunits of serine palmitoyltransferase, ssSPTs, are glycoproteins and are part of the enzyme complex
phosphoprotein
additional information
-
carrier lipid during extraction required for activity
phosphoprotein
phosphorylation of serine palmitoyltransferase long chain-1 (SPTLC1) on tyrosine 164 by the fusion kinase ABL inhibits the SPTLC1 enzyme activity. ABL-mediated phosphorylation of SPTLC1 affects its endoplasmic reticulum localization
phosphoprotein
phosphorylation of serine palmitoyltransferase long chain-1 (SPTLC1) on tyrosine 164 by the fusion kinase BCR-ABL inhibits the SPTLC1 enzyme activity. Inhibition of BCR-ABL kinase using either imatinib or shRNA-mediated silencing leads to the activation of SPTLC1 and to increased apoptosis in both K562 and LAMA-84 cells. ABL-mediated phosphorylation of SPTLC1 affects its endoplasmic reticulum localization
phosphoprotein
the enzyme is phosphorylated at S284 regulating its substrate specificity
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Crystallization/COMMENTARY
ORGANISM
UNIPROT
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 20°C, 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
-
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
-
determination of the crystal structure of enzyme mutant K265A that diffract to 1.6 A resolution and contain a canonical dimer in the asymmetric unit. Crystallization of the wild-type SPT:PLP-myriocin aldimine complex is not possible, most likely due to aldimine degradation
-
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
-
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pH STABILITY
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
6.8 - 8.5
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TEMPERATURE STABILITY
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
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STORAGE STABILITY
ORGANISM
UNIPROT
LITERATURE
4°C, Tris-HCl 20 mM, in sterile capped vials, 2 months without loss of activity
-
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Purification/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
immobilized metal ion affinity chromatography (Ni2+), gel filtration
-
native and recombinant from E. coli, LCB1 and LCB2 co-immunoprecipitate
-
purified as a water-soluble active homodimer
recombinant His-tagged enzyme from Escherichia coli strain BL21(DE3) by nickel affinity chromatography
recombinant His-tagged wild-type and enzyme and mutants V246M and G385F from Escherichia coli strain BL21(DE3) by nickel affinity chromatography
-
recombinant His-tagged wild-type and mutant enzymes from Escherichia coli strain BL21(DE3) by nickel affinity chromatography and gel filtration
-
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Cloned/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
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 Escherichia coli
expressed in yeast and mammalian cells, a triple fusion protein of the three subunits expressed in yeast and mammalian cells
-
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
-
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
-
expression of wild-type and mutant enzymes in HEK-293 cells. The overexpression of wild-type subunit SPTLC1 does not increase SPT enzyme activity compared with controls (empty vector), whereas overexpressing subunit SPTLC2 results in a 2fold increase in enzyme activity
expression of wild-type and mutant smalll subunits isoforms of serine palmitoyltransferase in yeast microsomes
-
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 different substrate preference, independently expressed domains of the viral SPT reassemble into an active protein, overview
-
His-tagged protein expressed in Escherichia coli BL21(DE3)
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
overexpression in Escherichia coli BL21 (DE3) pLysS, DNA sequence determination
-
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
-
recombinant expression of FLAG-tagged enzyme subunit LCB1 and of Myc-tagged enzyme subunit LCB2 in Saccharomyces cerevisiae microsomes. Expressing the Arabidopsis thaliana LCB1/LCB2 heterodimers has very low SPT activity, whereas coexpression of Arabidopsis thaliana ssSPTs, ssSPTa and ssSPTb, derived 56-amino acid polypeptides in a Saccharomyces cerevisiae enzyme SPT null mutant and stimulate SPT enzyme activity of the Arabidopsis LCB1/LCB2 heterodimer by over 100fold through physical interaction with LCB1/LCB2. Transient Agrobacterium tumefaciens-mediated transformation of Nicotiana benthaminana with YFP-labeled small subunits of serine palmitoyltransferase, ssSPTa and ssSPTb
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recombinant expression of His-tagged wild-type and mutant enzymes in Escherichia coli strain BL21(DE3)
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recombinant expression of ssSPTa, tagged with EGFP at its N-terminus, in HEK-293 cells
recombinant expression of subunit LCB2a mutants in HEK293 cells, recombinant His-tagged enzyme expression in Escherichia coli strain BL21(DE3). Recombinant expression of wild-type hLCB1/hLCB2a subunits in Saccharomyces cerevisiae microsomes in the absence of either small subunit, the enzyme shows very low activity. Coexpression of each of the three subunit hLCB2a mutants, V359M, G382V, and I504F, along with subunit hLCB1 results in low activity, with G382V barely detectable above background
recombinant stable expression of mutant and wild-type SPTLC2 subunit in HEK293 cells
RT-PCR from mRNA of Molt-4 cells; RT-PCR from mRNA of Molt-4 cells
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
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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
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subunit LCB1, DNA and amino acid sequence determination and analysis; subunit LCB2
B3Y000;, B3Y9H2;
subunits LCB1 and LCB2 expression analysis; subunits LCB1 and LCB2 expression analysis
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
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EXPRESSION
ORGANISM
UNIPROT
LITERATURE
imatinib does not affect SPTLC1 expression
LCB2 is upregulated during hypersensitive cell death nduced by the Phytophthora boehmeriae elicitor PB90
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
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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
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ENGINEERING
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
K311E
construction of mutant BcLCB2DELTAK311E that shows reduced activity compared to the wild-type enzyme
C133W
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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
R246G
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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
A182P
naturally occuring mutation in subunit LCB1 involved in hereditary sensory and autonomic neuropathy type I disease, and associated with increased synthesis of neurotoxic 1-deoxy-sphingolipids
A352V
subunit 1, naturally occuring mutation, reduced activity in cells expressing mutant protein
C133W
C133Y
G246R
expression of mutant G246R in in LYB cells, which is the same mutation that is present in LYB endogenously, neither restores canonical activity nor results in the formation of 1-deoxy-sphingolipids
G382V
I504F
I505Y
naturally occuring mutation in subunit LCB2 involved in hereditary sensory and autonomic neuropathy type I disease, and associated with increased synthesis of neurotoxic 1-deoxy-sphingolipids. The mutant shows an increased canonical activity and increased formation of C20 sphingoid base, associated with an exceptionally severe HSAN1 phenotype, where C20 sphingosine levels are also confirmed in plasma of patients
S331F
S331Y
naturally occuring mutation in subunit LCB1 involved in hereditary sensory and autonomic neuropathy type I disease, and associated with increased synthesis of neurotoxic 1-deoxy-sphingolipids.The mutant shows an increased canonical activity and increased formation of C20 sphingoid base, associated with an exceptionally severe HSAN1 phenotype, where C20 sphingosine levels are also confirmed in plasma of patients
S384A
a subunit SPTLC2 phosphorylation site mutant, the mutation has no effect n enzyme activity
S384D
a subunit SPTLC2 phosphorylation site mutant, the mutation is associated with increased 1-deoxysphingolipids formation
S384E
a subunit SPTLC2 phosphorylation site mutant, the mutation is not associated with increased 1-deoxysphingolipids formation
S384F
V359M
Y164F
site-directed mutagenesis, the mutant shows increased serine palmitoyltransferase activity compared to the wild-type enzyme. The Y164F mutation also promotes the remodeling of cellular sphingolipid content, thereby sensitizing K562 cells to apoptosis. the Y164F mutation affects SPTLC1 subcellular localization, induction of apoptosis, and sell sensitivity to imatinib
Y387F
a subunit SPTLC2 phosphorylation site mutant, the mutation has no effect n enzyme activity
Y387F/S384A
a subunit SPTLC2 phosphorylation sites mutant, the mutation has no effect n enzyme activity
DELTA2-9SPT
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mutant bearing deleted residues from Ala2 to Pro9: Km values are not significantly changed compared to wild-type
G268V
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site-directed mutagenesis, the mutation perturbs the pyridoxal 5'-phosphate cofactor binding and reduces the affinity for both substrates, inactive mutant, the protein is expressed in a completely insoluble form, structure homology modeling of the mutant enzyme using the Sp SPT PLP-L-serine external aldimine structure, PDB ID 2W8J
G385F
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site-directed mutagenesis, the mutation perturbs the pyridoxal 5'-phosphate cofactor binding, reduces the affinity for both substrates, decreases the enzyme activity, soluble protein
H159A
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site-directed mutagenesis, the mutant shows reduced activity and still forms the pyridoxal 5'-phosphate-L-serine-aldimine reaction intermediate
H159F
K265A
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site-directed mutagenesis, the mutant is unable to bind pyridoxal 5'-phosphate, structure of a SPT K265A:PLP-myriocin external aldimine complex, molecular replacement study
N100C
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site-directed mutagenesis, the mutation mimics the wild-type human enzyme and is fully active, crystal structure analysis
N100W
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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
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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
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site-directed mutagenesis, crystal structure analysis, the mutant is less able to stabilize a quinonoid intermediate
R378N
V246M
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site-directed mutagenesis, the mutation perturbs the pyridoxal 5'-phosphate cofactor binding, reduces the affinity for both substrates, decreases the enzyme activity, soluble protein
N100C
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site-directed mutagenesis, the mutation mimics the wild-type human enzyme and is fully active, crystal structure analysis
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N100W
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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
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N100Y
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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
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R378A
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site-directed mutagenesis, crystal structure analysis, the mutant is less able to stabilize a quinonoid intermediate
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R370A
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strictly conserved in all prokaryotic enzymes and the Icb2 subunit of eukaryotic enzymes, no catalytic activity
R370K
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strictly conserved in all prokaryotic enzymes and the Icb2 subunit of eukaryotic enzymes, 3% catalytic activity of wild type enzyme
additional information