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Literature summary for 3.2.1.183 extracted from

  • Ko, T.P.; Lai, S.J.; Hsieh, T.J.; Yang, C.S.; Chen, Y.
    The tetrameric structure of sialic-acid-synthesizing UDP-GlcNAc 2-epimerase from Acinetobacter baumannii a comparative study with human GNE (2018), J. Biol. Chem., 293, 10119-10127 .
    View publication on PubMedView publication on EuropePMC
Search for more literature for 3.2.1.183

Activating Compound

Activating Compound Comment Organism Structure
additional information the binding of UDP-GlcNAc to an allosteric site may stabilize the closed, active conformation of the enzyme, whereas the open form seems to be not active Homo sapiens

Protein Variants

Protein Variants Comment Organism
D143A the GNE catalytic site mutant completely loses its activity Homo sapiens

General Stability

General Stability Organism
the binding of UDP-GlcNAc to an allosteric site may stabilize the closed, active conformation of the enzyme, whereas the open form seems to be not active Homo sapiens

Inhibitors

Inhibitors Comment Organism Structure
CMP-Neu5Ac the downstream product CMP-Neu5Ac also acts as a feed-back inhibitor to regulate the GNE activity. The feedback inhibitor binds to the dimer-dimer interface and locks the tetramer into a tightly closed and inactive conformation. This is distinct from the activation mechanism of the non-hydrolyzing enzyme through a closed conformation Homo sapiens
UDP allosteric inhibition of enzyme GNE Homo sapiens

Natural Substrates/ Products (Substrates)

Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
UDP-N-acetyl-alpha-D-glucosamine + H2O Homo sapiens
-
 N-acetyl-D-mannosamine + UDP
-
 ?

Organism

Organism UniProt Comment Textmining
Homo sapiens Q9Y223
-
-

Reaction

Reaction Comment Organism Reaction ID
UDP-N-acetyl-alpha-D-glucosamine + H2O = N-acetyl-D-mannosamine + UDP catalytic and regulatory mechanisms Homo sapiens
a

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
UDP-N-acetyl-alpha-D-glucosamine + H2O
-
 Homo sapiens N-acetyl-D-mannosamine + UDP
-
 ?

Subunits

Subunits Comment Organism
dimer
-
 Homo sapiens
More the epimerase part of the bifunctional UDP-GlcNAc 2-epimerase/ManNAc kinase (GNE) folds into two Rossmann-like domains and forms dimers and tetramers Homo sapiens
tetramer
-
 Homo sapiens

Synonyms

Synonyms Comment Organism
bifunctional UDP-GlcNAc 2-epimerase/ManNAc kinase
-
 Homo sapiens
bifunctional UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase UniProt Homo sapiens
GNE
-
 Homo sapiens
hydrolyzing epimerase
-
 Homo sapiens
hydrolyzing UDP-GlcNAc 2-epimerase
-
 Homo sapiens
More cf. EC 2.7.1.60 Homo sapiens
UDP-GlcNAc 2-epimerase
-
 Homo sapiens
UDP-GlcNAc-2-epimerase/ManAc kinase UniProt Homo sapiens

General Information

General Information Comment Organism
malfunction impaired feed-back inhibition of the enzyme by CMP-Neu5Ac to regulate the GNE activity can result in sialuria Homo sapiens
metabolism the biosynthesis of sialic acids starts with hydrolytic epimerization of N-acetyl glucosamine (GlcNAc), catalyzed by UDP-GlcNAc 2-epimerase and producing N-acetyl mannosamine (ManNAc), which then reacts with phosphoenolpyruvate to form Neu5Ac. Whereas the substrate for non-hydrolyzing epimerase and hydrolyzing epimerase is the same, in this case, UDP-GlcNAc, the product of the former is UDP-ManNAc, and that of the latter is alpha-ManNAc plus UDP Homo sapiens
additional information the binding of UDP-GlcNAc to an allosteric site may stabilize the closed, active conformation of the enzyme, whereas the open form seems to be not active. Residue D143 is essential for catalytic activity Homo sapiens