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Literature summary for 6.3.4.4 extracted from

  • 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 (2010), Biochim. Biophys. Acta, 1804, 1996-2002.
    View publication on PubMed
Search for more literature for 6.3.4.4

Activating Compound

Activating Compound Comment Organism Structure
D-fructose 1,6 bisphosphate binds to the Asp loop and induces a conformation that facilitates aspartate binding to the enzyme active site Plasmodium falciparum

Cloned(Commentary)

Cloned (Comment) Organism
expression in Escherichia coli Plasmodium falciparum

Protein Variants

Protein Variants Comment Organism
K62L increase in Km values for IMP, GTP and aspartate, respectively Plasmodium falciparum
N429V increase in Km values for IMP, GTP and aspartate, respectively, along with a 5 fold drop in the kcat value Plasmodium falciparum
R155A residue influences both ligand binding and catalysis Plasmodium falciparum
R155A/G146R unlike dimeric wild-type, mainly monomeric. Inactive Plasmodium falciparum
R155K residue influences both ligand binding and catalysis Plasmodium falciparum
R155L residue influences both ligand binding and catalysis Plasmodium falciparum
T307V increase in Km values for IMP, GTP and aspartate, respectively Plasmodium falciparum

Inhibitors

Inhibitors Comment Organism Structure
phosphate competitive with aspartate Plasmodium falciparum

KM Value [mM]

KM Value [mM] KM Value Maximum [mM] Substrate Comment Organism Structure
0.0167
-
 IMP wild-type, pH 7.0, 37°C Plasmodium falciparum
0.0205
-
 IMP wild-type, pH 7.0, 25°C Plasmodium falciparum
0.0216
-
 IMP mutant K62L, pH 7.0, 37°C Plasmodium falciparum
0.0248
-
 GTP wild-type, pH 7.0, 37°C Plasmodium falciparum
0.027
-
 GTP wild-type, pH 7.0, 25°C Plasmodium falciparum
0.027
-
 GTP mutant N429V, pH 7.0, 37°C Plasmodium falciparum
0.0278
-
 GTP mutant R155L, pH 7.0, 25°C Plasmodium falciparum
0.0285
-
 IMP mutant T307V, pH 7.0, 37°C Plasmodium falciparum
0.0347
-
 GTP mutant T307V, pH 7.0, 37°C Plasmodium falciparum
0.0386
-
 GTP mutant R155K, pH 7.0, 25°C Plasmodium falciparum
0.0465
-
 GTP mutant K62L, pH 7.0, 37°C Plasmodium falciparum
0.0497
-
 IMP mutant N429V, pH 7.0, 37°C Plasmodium falciparum
0.31
-
 L-Asp wild-type, pH 7.0, 37°C Plasmodium falciparum
0.37
-
 L-Asp wild-type, pH 7.0, 25°C Plasmodium falciparum
0.48
-
 L-Asp mutant R155K, pH 7.0, 25°C Plasmodium falciparum
0.557
-
 IMP mutant R155K, pH 7.0, 25°C Plasmodium falciparum
0.57
-
 L-Asp mutant N429V, pH 7.0, 37°C Plasmodium falciparum
0.78
-
 L-Asp mutant K62L, pH 7.0, 37°C Plasmodium falciparum
1.1
-
 L-Asp mutant T307V, pH 7.0, 37°C Plasmodium falciparum
1.32
-
 L-Asp mutant R155L, pH 7.0, 25°C Plasmodium falciparum
2.554
-
 IMP mutant R155L, pH 7.0, 25°C Plasmodium falciparum

Molecular Weight [Da]

Molecular Weight [Da] Molecular Weight Maximum [Da] Comment Organism
48000
-
 gel filtration, mutant R155A/G146R, plus small peak of dimeric enzyme Plasmodium falciparum
50000
-
 2 * 50000, calculated, wild-type Plasmodium falciparum
92000
-
 gel filtration, wild-type and mutants N429V, K62L, T307V, R155V, R155K, R155A Plasmodium falciparum

Organism

Organism UniProt Comment Textmining
Plasmodium falciparum Q9U8D3
-
-

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
GTP + IMP + L-Asp
-
 Plasmodium falciparum GDP + phosphate + adenylosuccinate
-
 ?

Subunits

Subunits Comment Organism
dimer 2 * 50000, calculated, wild-type Plasmodium falciparum
More conserved arginine residue R155 is involved in dimer crosstalk and interacts with IMP in the active site of the symmetry related subunit Plasmodium falciparum

Turnover Number [1/s]

Turnover Number Minimum [1/s] Turnover Number Maximum [1/s] Substrate Comment Organism Structure
0.0038
-
 IMP mutant R155A, pH 7.0, 25°C Plasmodium falciparum
0.01
-
 IMP mutant R155L, pH 7.0, 25°C Plasmodium falciparum
0.112
-
 IMP mutant R155K, pH 7.0, 25°C Plasmodium falciparum
0.32
-
 IMP mutant N429V, pH 7.0, 37°C Plasmodium falciparum
1
-
 IMP wild-type, pH 7.0, 25°C Plasmodium falciparum
1.09
-
 IMP mutant K62L, pH 7.0, 37°C Plasmodium falciparum
1.44
-
 IMP wild-type, pH 7.0, 37°C Plasmodium falciparum
1.72
-
 IMP mutant T307V, pH 7.0, 37°C Plasmodium falciparum

Ki Value [mM]

Ki Value [mM] Ki Value maximum [mM] Inhibitor Comment Organism Structure
28
-
 phosphate pH 7.0, 37°C Plasmodium falciparum