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Information on EC 6.3.4.4 - adenylosuccinate synthase and Organism(s) Plasmodium falciparum and UniProt Accession Q9U8D3
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6.3.4.4 adenylosuccinate synthaseSpecify your search results
Word Map
- 6.3.4.4
- purine
- gtp
- inosine
- hadacidin
- hypoxanthine
- formycin
- adenylosuccinase
-
alanosine
- medicine
-
saicar
- synthesis
- agriculture
The taxonomic range for the selected organisms is: Plasmodium falciparum
The enzyme appears in selected viruses and cellular organisms
The enzyme appears in selected viruses and cellular organisms
Synonyms
adenylosuccinate synthetase, adssl1, adss1, adenylosuccinate synthase, pfadss, adss2, ampss, succino-amp synthetase, adenylosuccinate synthetase 1, mouse muscle synthetase, 
more
topSYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
Adenylosuccinate synthase
-
-
-
-
Adenylosuccinate synthetase
AdSS
AMPSase
-
-
-
-
IMP--aspartate ligase
-
-
-
-
IMP-aspartate ligase
-
-
-
-
Succino-AMP synthetase
-
-
-
-
Succinoadenylic kinosynthetase
-
-
-
-
Adenylosuccinate synthetase
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-
-
-
AdSS
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-
-
-
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
amination
-
-
-
-
PATHWAY SOURCE
PATHWAYS
BRENDA
-
-
SYSTEMATIC NAME
IUBMB Comments
IMP:L-aspartate ligase (GDP-forming)
-
CAS REGISTRY NUMBER
COMMENTARY
9023-57-8
-
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
GTP + IMP + L-Asp
GDP + phosphate + adenylosuccinate
-
-
-
?
GTP + IMP + L-aspartate
GDP + phosphate + adenylosuccinate
-
-
?
GTP + IMP + L-aspartate
GDP + phosphate + adenylosuccinate
salvage pathway, catalyzing the first committed step in the synthesis of AMP from IMP
-
?
GTP + IMP + L-aspartate
GDP + phosphate + adenylosuccinate
-
-
-
?
GTP + IMP + L-aspartate
GDP + phosphate + adenylosuccinate
-
salvage pathway
-
?
NATURAL SUBSTRATE
NATURAL 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
GTP + IMP + L-aspartate
GDP + phosphate + adenylosuccinate
salvage pathway, catalyzing the first committed step in the synthesis of AMP from IMP
-
?
GTP + IMP + L-aspartate
GDP + phosphate + adenylosuccinate
-
salvage pathway
-
?
COFACTOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
adenylosuccinate
-
competitive versus IMP, non-competitive versus GTP and aspartate
AMP
-
competitive versus IMP, non-competitive versus GTP and non-competitive versus aspartate
GDP
-
uncompetitive versus IMP, competitive versus GTP and non-competitive versus aspartate
GMP
-
uncompetitive versus IMP, competitive versus GTP and non-competitive versus aspartate
Hadacidin
-
uncompetitive versus IMP and GTP, competitive versus aspartate
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
D-fructose 1,6 bisphosphate
binds to the Asp loop and induces a conformation that facilitates aspartate binding to the enzyme active site
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.0172
GTP
mutant enzyme C328S/C368S, in 30 mM sodium phosphate, pH 7.4 and at 25°C
0.0206
GTP
mutant enzyme C368S, in 30 mM sodium phosphate, pH 7.4 and at 25°C
0.0248
GTP
wild type enzyme, in 30 mM sodium phosphate, pH 7.4 and at 25°C
0.0251
GTP
mutant enzyme C328D, in 30 mM sodium phosphate, pH 7.4 and at 25°C
0.0358
GTP
mutant enzyme C368D/C368D, in 30 mM sodium phosphate, pH 7.4 and at 25°C
0.044
GTP
mutant enzyme C328S, in 30 mM sodium phosphate, pH 7.4 and at 25°C
0.0152
IMP
mutant enzyme C328S, in 30 mM sodium phosphate, pH 7.4 and at 25°C
0.0168
IMP
wild type enzyme, in 30 mM sodium phosphate, pH 7.4 and at 25°C
0.0198
IMP
mutant enzyme C328S/C368S, in 30 mM sodium phosphate, pH 7.4 and at 25°C
0.0248
IMP
mutant enzyme C368S, in 30 mM sodium phosphate, pH 7.4 and at 25°C
0.0276
IMP
mutant enzyme C328D, in 30 mM sodium phosphate, pH 7.4 and at 25°C
0.0292
IMP
mutant enzyme C368D/C368D, in 30 mM sodium phosphate, pH 7.4 and at 25°C
0.49
L-Asp
mutant enzyme C328S/C368S, in 30 mM sodium phosphate, pH 7.4 and at 25°C
1.4
L-Asp
mutant enzyme C328D, in 30 mM sodium phosphate, pH 7.4 and at 25°C
1.73
L-Asp
mutant enzyme C368D/C368D, in 30 mM sodium phosphate, pH 7.4 and at 25°C
1.9
L-Asp
mutant enzyme C328S, in 30 mM sodium phosphate, pH 7.4 and at 25°C
1.9
L-Asp
wild type enzyme, in 30 mM sodium phosphate, pH 7.4 and at 25°C
3.3
L-Asp
mutant enzyme C368S, in 30 mM sodium phosphate, pH 7.4 and at 25°C
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.62
IMP
mutant enzyme C328S/C368S, in 30 mM sodium phosphate, pH 7.4 and at 25°C
0.7
IMP
mutant enzyme C368D/C368D, in 30 mM sodium phosphate, pH 7.4 and at 25°C
0.84
IMP
mutant enzyme C328S, in 30 mM sodium phosphate, pH 7.4 and at 25°C
1
IMP
mutant enzyme C368S, in 30 mM sodium phosphate, pH 7.4 and at 25°C
1.1
IMP
wild type enzyme, in 30 mM sodium phosphate, pH 7.4 and at 25°C
1.7
IMP
mutant enzyme C328D, in 30 mM sodium phosphate, pH 7.4 and at 25°C
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
pH RANGE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable).
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable). PURA_PLAFA
442
0
50065
Swiss-Prot
other Location (Reliability: 2)
PDB
SCOP
CATH
UNIPROT
ORGANISM
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
48000
gel filtration, mutant R155A/G146R, plus small peak of dimeric enzyme
50000
92000
gel filtration, wild-type and mutants N429V, K62L, T307V, R155V, R155K, R155A
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
dimer
additional information
additional information
conserved arginine residue R155 is involved in dimer crosstalk and interacts with IMP in the active site of the symmetry related subunit
additional information
-
conserved arginine residue R155 is involved in dimer crosstalk and interacts with IMP in the active site of the symmetry related subunit
CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
space group C222(1), cell parameters a = 91.58 A, b = 117.12 A, c = 80.42A
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
C328D
the mutant shows reduced Km and increased turnover number for L-aspartate compared to the wild type protein
C328D/C368D
the mutant shows reduced Km and turnover number for L-aspartate compared to the wild type protein
C328S
the mutant exhibits no change in the aspartate Km value but reduced turnover number compared to the wild type protein
C328S/C368S
the mutant shows a 4fold reduced Km for aspartate and reduced turnover number compared to the wild type protein
C368S
the mutant exhibits a 1.7fold increase in the aspartate Km value compared to the wild type protein
K62L
increase in Km values for IMP, GTP and aspartate, respectively
N429V
increase in Km values for IMP, GTP and aspartate, respectively, along with a 5 fold drop in the kcat value
R155A/G146R
unlike dimeric wild-type, mainly monomeric. Inactive
T307V
increase in Km values for IMP, GTP and aspartate, respectively
GENERAL STABILITY
ORGANISM
UNIPROT
LITERATURE
at 1.5 M urea the enzyme dissociates to form monomers and further increase in urea concentration causes unfolding of this species
requires presence of dithiothreitol during the entire course of purification for activity
-
STORAGE STABILITY
ORGANISM
UNIPROT
LITERATURE
4°C, glycerol and EDTA stabilizes enzyme activity during storage, stable for at least 3 weeks
-
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
ammonium sulfate precipitation, anion exchange chromatography, and gel filtration
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
hyperexpressed in Escherichia coli BL21 (DE3), complementation of purA mutant strain H1238
-
APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
medicine
enzymes of the salvage pathway are good targets for anti-parasitic drugs
medicine
-
most parasitic protozoa lack the de novo purine biosynthetic pathway and rely exclusively on the salvage pathway for their purine biosynthetic pathway, enzymes of the salvage pathway are candidate drug targets
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Eaazhisai, K.; Jayalakshmi, R.; Gayathri, P.; Anand, R.P.; Sumathy, K.; Balaram, H.; Murthy, M.R.
Crystal structure of fully ligated adenylosuccinate synthetase from Plasmodium falciparum
J. Mol. Biol.
335
1251-1264
2004
Plasmodium falciparum (Q9U8D3), Plasmodium falciparum
Jayalakshmi, R.; Sumathy, K.; Balaram, H.
Purification and characterization of recombinant Plasmodium falciparum adenylosuccinate synthetase expressed in Escherichia coli
Protein Expr. Purif.
25
65-72
2002
Plasmodium falciparum
Raman, J.; Mehrotra, S.; Anand, R.P.; Balaram, H.
Unique kinetic mechanism of Plasmodium falciparum adenylosuccinate synthetase
Mol. Biochem. Parasitol.
138
1-8
2004
Plasmodium falciparum
Mehrotra, S.; Mylarappa, B.N.; Iyengar, P.; Balaram, H.
Studies on active site mutants of P. falciparum adenylosuccinate synthetase: insights into enzyme catalysis and activation
Biochim. Biophys. Acta
1804
1996-2002
2010
Plasmodium falciparum (Q9U8D3), Plasmodium falciparum
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