Any feedback?
Literature summary extracted from
- Multiple functionalities of reduced flavin in the non-redox reaction catalyzed by UDP-galactopyranose mutase (2017), Arch. Biochem. Biophys., 632, 59-65 .
Crystallization (Commentary)
| EC Number | Crystallization (Comment) | Organism |
|---|---|---|
| 5.4.99.9 | the structure of enzyme mutant AfUGMH63A complexed with the substrate UDP-Galp shows the presence of a C1-galactose-N5-FAD adduct (PDB ID 5HHF), a covalent intermediate bound to AfUGMH63A | Aspergillus fumigatus |
Protein Variants
| EC Number | Protein Variants | Comment | Organism |
|---|---|---|---|
| 5.4.99.9 | H63N | site-directed mutagenesis, the structure of enzyme mutant AfUGMH63A complexed with the substrate UDP-Galp shows the presence of a C1-galactose-N5-FAD adduct (PDB ID 5HHF) | Aspergillus fumigatus |
Natural Substrates/ Products (Substrates)
| EC Number | Natural Substrates | Organism | Comment (Nat. Sub.) | Natural Products | Comment (Nat. Pro.) | Rev. | Reac. |
|---|---|---|---|---|---|---|---|
| 5.4.99.9 | UDP-alpha-D-galactopyranose | Aspergillus fumigatus | - |
UDP-alpha-D-galactofuranose | - |
r |  |
Organism
| EC Number | Organism | UniProt | Comment | Textmining |
|---|---|---|---|---|
| 5.4.99.9 | Aspergillus fumigatus | Q4W1X2 | i.e. Neosartorya fumigata | - |
Reaction
| EC Number | Reaction | Comment | Organism | Reaction ID |
|---|---|---|---|---|
| 5.4.99.9 | UDP-alpha-D-galactopyranose = UDP-alpha-D-galactofuranose | reaction mechanism including FAD cofactor, overview. Role of a covalent flavin N5 intermediate in the isomerization, non-redox reaction, of UDP-galactopyranose (UDP-Galp) to UDP-galactofuranose (UDP-Galf) by UDP-galactopyranose mutase (UGM). The flavin is required to be in the reduced state and functions as a nucleophile. The flavin must cycle back to the oxidized state for sustained catalysis. Formation of a N5-iminium ion intermediate, Fformation of N5-adducts in non-redox reactions involving the flavin in the oxidized or reduced forms | Aspergillus fumigatus |
Substrates and Products (Substrate)
| EC Number | Substrates | Comment Substrates | Organism | Products | Comment (Products) | Rev. | Reac. |
|---|---|---|---|---|---|---|---|
| 5.4.99.9 | UDP-alpha-D-galactopyranose | - |
Aspergillus fumigatus | UDP-alpha-D-galactofuranose | - |
r | |
Synonyms
| EC Number | Synonyms | Comment | Organism |
|---|---|---|---|
| 5.4.99.9 | UGM | - |
Aspergillus fumigatus |
Cofactor
| EC Number | Cofactor | Comment | Organism | Structure |
|---|---|---|---|---|
| 5.4.99.9 | FAD | the flavin functions as a catalytic center in a non-redox reaction, catalytic function, overview. The flavin is required to be in the reduced state and functions as a nucleophile. The flavin must cycle back to the oxidized state for sustained catalysis | Aspergillus fumigatus | |
General Information
| EC Number | General Information | Comment | Organism |
|---|---|---|---|
| 5.4.99.9 | evolution | the enzyme belongs to the group of flavoenzymes, a unifying concept of flavin hot spots is introduced to understand and categorize the mechanisms and reactivities of both traditional and noncanonical flavoenzymes. The major hot spots of reactivity include the N5, C4a, and C4O atoms of the isoalloxazine, and the 20 hydroxyl of the ribityl chain. The role of hot spots in traditional flavoenzymes, such as monooxygenases, and description of flavin hot spots in noncanonical flavoenzymes, overview | Aspergillus fumigatus |
| 5.4.99.9 | malfunction | without residue His63, the distance between the FAD C4OH and the Galp O5 is not decreased by bending of the flavin ring preventing the proton transfer step. Therefore, the reaction will stall at the FAD-Galp step, accounting for why this intermediate is observed in the AfUGMH63A structure | Aspergillus fumigatus |
| 5.4.99.9 | additional information | analysis of the structure of the UGM adduct in combination with quantum mechanics/molecular mechanics (QM/MM) molecular dynamics studies, overview. The simulations indicate that after formation of the N5-galactose adduct, the next step is deprotonation of the N5-atom by the C4O. The distance between the N5-H and the C4O in the reduced FAD is 2.4 A (from about 2.7 A in the oxidized form) due to bending of the flavin. Molecular dynamics simulations indicate that the bending is further increased in the transition state, decreasing the distance between these two atoms to 1.5 A. This process is stabilized by interactions of the positively charged His63 with the electron rich flavin. The next step in the reaction is opening of the sugar ring. This step is coupled to the formation of the N5-iminum ion and is facilitated by protonation of Galp O5 atom. Bending of the flavin, which brings the FAD C4OH and the Galp O5 together for proton transfer, is also required in this step. The Galp O5 atom is shifts 1.2 A towards the FAD C4O in the FADGalp adduct structure. Formation of the FAD-Galp-iminium ion activates the Galp C1 for attack by the C4-OH to generate the furanose form of the sugar. Deprotonation of the sugar C4-OH prior to this step is facilitated by the FAD C4O atom. The proton now at the FAD C4O position is then transferred back to the FAD N5 atom. The final step is the attack of the Galf C1 by UDP to form UDP-Galf, which yields the reduced flavin | Aspergillus fumigatus |
Use of this online version of BRENDA is free under the CC BY 4.0 license. See terms of use for full details.
Release 2023.1 (January 2023)
Legal
Curated at
Member of
