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Information on EC 4.3.1.17 - L-serine ammonia-lyase and Organism(s) Homo sapiens and UniProt Accession Q96GA7

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EC Tree
     4 Lyases
         4.3 Carbon-nitrogen lyases
             4.3.1 Ammonia-lyases
                4.3.1.17 L-serine ammonia-lyase
IUBMB Comments
Most enzymes that catalyse this reaction are pyridoxal-phosphate-dependent, although some enzymes contain an iron-sulfur cluster instead . The reaction catalysed by both types of enzymes involves the initial elimination of water to form an enamine intermediate (hence the enzyme's original classification as EC 4.2.1.13, L-serine dehydratase), followed by tautomerization to an imine form and hydrolysis of the C-N bond. The latter reaction, which can occur spontaneously, is also be catalysed by EC 3.5.99.10, 2-iminobutanoate/2-iminopropanoate deaminase. This reaction is also carried out by EC 4.3.1.19, threonine ammonia-lyase, from a number of sources.
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This record set is specific for:
Homo sapiens
UNIPROT: Q96GA7
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The taxonomic range for the selected organisms is: Homo sapiens
The expected taxonomic range for this enzyme is: Bacteria, Eukaryota, Archaea
Reaction Schemes
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L-serine
=
pyruvate
+
NH3
=
+
Synonyms
serine dehydratase, l-serine dehydratase, l-threonine deaminase, l-threonine dehydratase, l-serine deaminase, serine deaminase, serdh, lplsd, l-sd2, msmeg_3532, more
SYNONYM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SDH-like-1
-
serine dehydratase like-1
-
cSDH
cancerous SDH
Dehydratase, L-serine
-
-
-
-
L-Hydroxy amino acid dehydratase
-
-
-
-
L-SD
-
-
-
-
L-SD1
-
-
-
-
L-SD2
-
-
-
-
L-serine ammonia-lyase
-
L-Serine deaminase
-
-
-
-
L-serine dehydratase
-
-
SD
-
-
-
-
Serine deaminase
-
-
-
-
Serine dehydratase
additional information
-
L-serine dehydratase and cystathionine beta-synthase are the same enzyme
REACTION
REACTION DIAGRAM
COMMENTARY hide
ORGANISM
UNIPROT
LITERATURE
L-serine = pyruvate + NH3
show the reaction diagram
catalytic mechanism
SYSTEMATIC NAME
IUBMB Comments
L-serine ammonia-lyase (pyruvate-forming)
Most enzymes that catalyse this reaction are pyridoxal-phosphate-dependent, although some enzymes contain an iron-sulfur cluster instead [6]. The reaction catalysed by both types of enzymes involves the initial elimination of water to form an enamine intermediate (hence the enzyme's original classification as EC 4.2.1.13, L-serine dehydratase), followed by tautomerization to an imine form and hydrolysis of the C-N bond. The latter reaction, which can occur spontaneously, is also be catalysed by EC 3.5.99.10, 2-iminobutanoate/2-iminopropanoate deaminase. This reaction is also carried out by EC 4.3.1.19, threonine ammonia-lyase, from a number of sources.
CAS REGISTRY NUMBER
COMMENTARY hide
9014-27-1
-
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
L-serine
pyruvate + NH3
show the reaction diagram
L-serine
D-serine
show the reaction diagram
-
racemization reaction
-
-
r
L-serine
pyruvate + NH3
show the reaction diagram
L-serine-O-sulfate
O-sulfopyruvate + NH3
show the reaction diagram
-
elimination reaction
-
-
?
L-threonine
2-oxobutyrate + NH3
show the reaction diagram
-
-
-
?
L-threonine
alpha-ketobutyrate + NH3
show the reaction diagram
-
-
-
?
NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
L-serine
pyruvate + NH3
show the reaction diagram
SDH is a pyridoxal 5'-phosphate-dependent enzyme that catalyzes dehydration of L-Ser/Thr to yield pyruvate/ketobutyrate and ammonia
-
-
?
L-serine
pyruvate + NH3
show the reaction diagram
COFACTOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
pyridoxal 5'-phosphate
SDH is a pyridoxal 5'-phosphate-dependent enzyme, PLP is covalently attached to K48 by Schiff-base linkage in the active site. The ring nitrogen of PLP is involved in a H-bonding with C309, but is apparently not protonated
pyridoxal 5'-phosphate
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
K+
-
stimulating
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
hydroxylamine
-
-
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
50
L-serine
pH 8.3, 37°C
57
L-threonine
pH 8.3, 37°C
30.7 - 67.3
serine
3.1 - 59.5
threonine
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
137
substrate L-serine, pH 8.3, 37°C
96
substrate L-threonine, pH 8.3, 37°C
additional information
-
-
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
8.3
assay at
8.3
activity assay
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
-
UniProt
Manually annotated by BRENDA team
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE
cancer cell line-specific isozyme cSDH
Manually annotated by BRENDA team
hSDH, mainly
Manually annotated by BRENDA team
hepatic SDH
Manually annotated by BRENDA team
cancerous SDH
Manually annotated by BRENDA team
cancerous SDH
Manually annotated by BRENDA team
UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION?
SDSL_HUMAN
329
0
34674
Swiss-Prot
other Location (Reliability: 3)
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
33000
2 * 33000, SDS-PAGE, 2 * 34702, calculated
34630
hSDH, calculated molecular weight
34670
cSDH, calculated molecular weight
34702
2 * 33000, SDS-PAGE, 2 * 34702, calculated
60000
gel filtration
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
dimer
2 * 33000, SDS-PAGE, 2 * 34702, calculated
additional information
CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
purified recombinant cSDH, hanging drop vapour diffusion method, 10 mg/ml protien in 50 mM Na-citrate, pH 5.6, 10 mM DL-O-methylserine, 200 mM potassium acetate, 5 mM dithiothreitol, 15% w/v PEG-8000 at 21°C, 1 week, X-ray diffraction structure determination and analysis at 2.8 A resolution
crystal structure obtained by molecular replacement shows a homodimer and a fold typical for beta-family pyridoxal 5'-phosphate-dependent enzymes. Each monomer serves as an active unit
-
hanging-drop vapour diffusion, 0.002 ml protein solution containing 20-30 mg/ml SDH in 20 mM Tris-HCl, pH 7.6 and 150 mM NaCl is mixed with 0.002 ml reservoir solution containing 800 mM ammonium sulfate in 100 mM Tris-HCl, pH 7.0-8.0, crystals diffract to 2.5 A
-
structure of A65S hSDH mutant is determined at 1.3 A resolution
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
A65G
site-directed mutagenesis of the human liver isozyme cSDH, large structural alterations, serine binding is not affected, overview
C303A
site-directed mutagenesis of the human liver isozyme cSDH, structural alterations, overview
C309A
site-directed mutagenesis of the cancer cell isozyme cSDH, structural alterations, overview
G72A
site-directed mutagenesis of the cancer cell isozyme cSDH, large structural alterations, serine binding is not affected, changing alanine to glycine at residue 72 in cSDH is responsible for the reduced catalytic activity of cSDH, overview
G72A/S228A
site-directed mutagenesis of the cancer cell isozyme cSDH, catalytic activities for both the substrates are substantially recovered, overview
A65S
structure of A65S hSDH mutant is determined at 1.3 A resolution. Mutant shows decreased activity (50%) with substrate L-serine compared to wild-type. Mutant shows measurable activity with substrate D-serine
A65S/V225S
double mutant shows only 10% of activity with substrate L-serine compared to wild-type (100%). Double mutant shows very little but measurable activity with substrate D-serine
cSDH-hSDH
chimeric protein
DELTAP128
hSDH
InsP128
cSDH, cSDH lacks a Pro residue corresponding to Pro128 in hSDH
TEMPERATURE STABILITY
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
45
-
10 min, stable up to
50
-
10 min, about 10% loss of activity
55
-
10 min, about 50% loss of activity
60
-
10 min, about 75% loss of activity
STORAGE STABILITY
ORGANISM
UNIPROT
LITERATURE
-80°C, stable for more than 2 weeks
0°C, stable for at least 2 weeks
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
recombinant cancer cell isozyme cSDH to homogeneity by ammonium sulfate fractionation, dialysis, anion exchange and nickel affinity chromatography
cSDH is purified using a Sephacryl S-200 and a Ni2+-NAT column
expression in Escherichia coli with N-terminal His-tag, purification protocol from inclusion bodies
-
recombinant protein expressed in Escherichia coli
recombinant SDH
-
using Ni-NTA chromatography
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
cancer cell isozyme cSDH, expression in Escherichia coli strain BL21
expressed in Escherichia coli as a His-tagged fusion protein
expression in Escherichia coli
-
the cSDH sequence is cloned into the pCW and pET28a vector for expression of the protein in Escherichia coli BL21DE3 cells
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Porter, P.N.; Grishaver, M.S.; Jones, O.W.
Characterization of human cystathionine beta-synthase. Evidence for the identity of human L-serine dehydratase and cystathionine beta-synthase
Biochim. Biophys. Acta
364
128-139
1974
Homo sapiens
Manually annotated by BRENDA team
Sun, L.; Li, X.; Dong, Y.; Yang, M.; Liu, Y.; Han, X.; Zhang, X.; Pang, H.; Rao, Z.
Crystallization and preliminary crystallographic analysis of human serine dehydratase
Acta Crystallogr. Sect. D
59
2297-2299
2003
Homo sapiens
Manually annotated by BRENDA team
Nagayoshi, C.; Ishibashi, M.; Kita, Y.; Matsuoka, M.; Nishimoto, I.; Tokunaga, M.
Expression, refolding and characterization of human brain serine racemase in Escherichia coli with N-terminal His-tag
Protein Pept. Lett.
12
487-490
2005
Homo sapiens
Manually annotated by BRENDA team
Kashii, T.; Gomi, T.; Oya, T.; Ishii, Y.; Oda, H.; Maruyama, M.; Kobayashi, M.; Masuda, T.; Yamazaki, M.; Nagata, T.; Tsukada, K.; Nakajima, A.; Tatsu, K.; Mori, H.; Takusagawa, F.; Ogawa, H.; Pitot, H.C.
Some biochemical and histochemical properties of human liver serine dehydratase
Int. J. Biochem. Cell Biol.
37
574-589
2005
Homo sapiens (P20132), Homo sapiens, Rattus norvegicus
Manually annotated by BRENDA team
Sun, L.; Bartlam, M.; Liu, Y.; Pang, H.; Rao, Z.
Crystal structure of the pyridoxal-5'-phosphate-dependent serine dehydratase from human liver
Protein Sci.
14
791-798
2005
Homo sapiens
Manually annotated by BRENDA team
Ogawa, H.; Gomi, T.; Nishizawa, M.; Hayakawa, Y.; Endo, S.; Hayashi, K.; Ochiai, H.; Takusagawa, F.; Pitot, H.C.; Mori, H.; Sakurai, H.; Koizumi, K.; Saiki, I.; Oda, H.; Fujishita, T.; Miwa, T.; Maruyama, M.; Kobayashi, M.
Enzymatic and biochemical properties of a novel human serine dehydratase isoform
Biochim. Biophys. Acta
1764
961-971
2006
Homo sapiens (P20132), Homo sapiens
Manually annotated by BRENDA team
Yamada, T.; Komoto, J.; Kasuya, T.; Takata, Y.; Ogawa, H.; Mori, H.; Takusagawa, F.
A catalytic mechanism that explains a low catalytic activity of serine dehydratase like-1 from human cancer cells: crystal structure and site-directed mutagenesis studies
Biochim. Biophys. Acta
1780
809-818
2008
Homo sapiens (Q96GA7), Homo sapiens
Manually annotated by BRENDA team
Wang, C.Y.; Ku, S.C.; Lee, C.C.; Wang, A.H.
Modulating the function of human serine racemase and human serine dehydratase by protein engineering
Protein Eng. Des. Sel.
25
741-749
2012
Homo sapiens (P20132), Homo sapiens
Manually annotated by BRENDA team