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Literature summary for 5.4.99.9 extracted from

  • Boechi, L.; de Oliveira, C.A.; Da Fonseca, I.; Kizjakina, K.; Sobrado, P.; Tanner, J.J.; McCammon, J.A.
    Substrate-dependent dynamics of UDP-galactopyranose mutase: implications for drug design (2013), Protein Sci., 22, 1490-1501.
    View publication on PubMedView publication on EuropePMC

Application

Application Comment Organism
drug development since the enzyme does not exist in Homo sapiens, the parasite enzyme is a target for drug design Trypanosoma cruzi

Crystallization (Commentary)

Crystallization (Comment) Organism
crystal structure analysis, molecular dynamics simulations and modeling, overview Trypanosoma cruzi

Protein Variants

Protein Variants Comment Organism
R176A site-directed mutagenesis, the mutant shows highly reduced activity compared to the wild-type enzyme Trypanosoma cruzi
R327A site-directed mutagenesis, the mutant shows reduced activity compared to the wild-type enzyme Trypanosoma cruzi
Y317F site-directed mutagenesis, the mutant shows highly reduced activity compared to the wild-type enzyme Trypanosoma cruzi
Y395F site-directed mutagenesis, the mutant shows reduced activity compared to the wild-type enzyme Trypanosoma cruzi
Y429F site-directed mutagenesis, the mutant shows reduced activity compared to the wild-type enzyme Trypanosoma cruzi

KM Value [mM]

KM Value [mM] KM Value Maximum [mM] Substrate Comment Organism Structure
0.0334
-
UDP-alpha-D-galactopyranose mutant Y317F, pH 7.5, 37°C Trypanosoma cruzi
0.09
-
UDP-alpha-D-galactopyranose mutant R327A, pH 7.5, 37°C Trypanosoma cruzi
0.091
-
UDP-alpha-D-galactopyranose mutant Y395F, pH 7.5, 37°C Trypanosoma cruzi
0.1
-
UDP-alpha-D-galactopyranose mutant Y429F, pH 7.5, 37°C Trypanosoma cruzi
0.134
-
UDP-alpha-D-galactopyranose mutant R176A, pH 7.5, 37°C Trypanosoma cruzi
0.14
-
UDP-alpha-D-galactopyranose wild-type enzyme, pH 7.5, 37°C Trypanosoma cruzi

Natural Substrates/ Products (Substrates)

Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
UDP-alpha-D-galactopyranose Trypanosoma cruzi
-
UDP-alpha-D-galactofuranose
-
r

Organism

Organism UniProt Comment Textmining
no activity in Homo sapiens
-
-
-
Trypanosoma cruzi
-
-
-

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
UDP-alpha-D-galactopyranose
-
Trypanosoma cruzi UDP-alpha-D-galactofuranose
-
r

Synonyms

Synonyms Comment Organism
UGM
-
Trypanosoma cruzi

Temperature Optimum [°C]

Temperature Optimum [°C] Temperature Optimum Maximum [°C] Comment Organism
37
-
assay at Trypanosoma cruzi

Turnover Number [1/s]

Turnover Number Minimum [1/s] Turnover Number Maximum [1/s] Substrate Comment Organism Structure
0.0224
-
UDP-alpha-D-galactopyranose mutant R176A, pH 7.5, 37°C Trypanosoma cruzi
0.248
-
UDP-alpha-D-galactopyranose mutant Y395F, pH 7.5, 37°C Trypanosoma cruzi
0.291
-
UDP-alpha-D-galactopyranose mutant Y317F, pH 7.5, 37°C Trypanosoma cruzi
4.26
-
UDP-alpha-D-galactopyranose mutant R327A, pH 7.5, 37°C Trypanosoma cruzi
6.296
-
UDP-alpha-D-galactopyranose mutant Y429F, pH 7.5, 37°C Trypanosoma cruzi
13.4
-
UDP-alpha-D-galactopyranose wild-type enzyme, pH 7.5, 37°C Trypanosoma cruzi

pH Optimum

pH Optimum Minimum pH Optimum Maximum Comment Organism
7.5
-
assay at Trypanosoma cruzi

Cofactor

Cofactor Comment Organism Structure
FAD
-
Trypanosoma cruzi

General Information

General Information Comment Organism
additional information molecular details of the mechanism that controls the uptake and retention of the substrate in the presence or absence of an active site ligand, overview. Interactions with the substrate diphosphate moiety are especially important for stabilizing the closed active site. Protein dynamics play a key role in substrate recognition by UDP-galactopyranose mutases. Residues Arg176, Asn201, and Tyr317, Tyr34, Tyr429, and Arg327 are involved in the active site Trypanosoma cruzi
physiological function the flavoenzyme UDP-galactopyranose mutase catalyzes the conversion of UDP-galactopyranose to UDP-galactofuranose, a precursor of the cell surface beta-galactofuranose that is involved in the virulence of the pathogen Trypanosoma cruzi

kcat/KM [mM/s]

kcat/KM Value [1/mMs-1] kcat/KM Value Maximum [1/mMs-1] Substrate Comment Organism Structure
0.00017
-
UDP-alpha-D-galactopyranose mutant R176A, pH 7.5, 37°C Trypanosoma cruzi
0.00087
-
UDP-alpha-D-galactopyranose mutant Y317F, pH 7.5, 37°C Trypanosoma cruzi
0.0027
-
UDP-alpha-D-galactopyranose mutant Y395F, pH 7.5, 37°C Trypanosoma cruzi
0.047
-
UDP-alpha-D-galactopyranose mutant R327A, pH 7.5, 37°C Trypanosoma cruzi
0.063
-
UDP-alpha-D-galactopyranose mutant Y429F, pH 7.5, 37°C Trypanosoma cruzi
0.093
-
UDP-alpha-D-galactopyranose wild-type enzyme, pH 7.5, 37°C Trypanosoma cruzi