5.4.99.9: UDP-galactopyranose mutase
This is an abbreviated version!
For detailed information about UDP-galactopyranose mutase, go to the full flat file.
Word Map on EC 5.4.99.9
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5.4.99.9
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phosphoglycerate
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methylmalonic
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methylmalonyl-coa
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udp-galactofuranose
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galactofuranose
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chorismate
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urogenital
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udp-galf
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acidemia
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galf
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adenosylcobalamin
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methylmalonyl-coenzyme
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sinus
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prephenate
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acidurias
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succinyl-coa
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b12-dependent
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2,3-bisphosphoglycerate
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bisphosphoglycerate
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flavoenzyme
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adocbl
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cobalamin-dependent
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propionyl-coa
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adenosylcobalamin-dependent
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drug development
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isobutyryl-coa
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cofactor-dependent
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shermanii
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cytodifferentiation
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methylcobalamin
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phosphoenzyme
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cobiialamin
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analysis
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medicine
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synthesis
- 5.4.99.9
- phosphoglycerate
-
methylmalonic
- methylmalonyl-coa
- udp-galactofuranose
-
galactofuranose
- chorismate
-
urogenital
-
udp-galf
- acidemia
-
galf
- adenosylcobalamin
-
methylmalonyl-coenzyme
-
sinus
- prephenate
- acidurias
- succinyl-coa
-
b12-dependent
- 2,3-bisphosphoglycerate
-
bisphosphoglycerate
-
flavoenzyme
-
adocbl
-
cobalamin-dependent
- propionyl-coa
-
adenosylcobalamin-dependent
- drug development
- isobutyryl-coa
-
cofactor-dependent
- shermanii
-
cytodifferentiation
- methylcobalamin
- phosphoenzyme
-
cobiialamin
- analysis
- medicine
- synthesis
Reaction
Synonyms
AfUGM, ANIA_03112, CdUGM, galactopyranose mutase, Glf, GLF gene product, GLF-1, glfA, MtUGM, mutase, Mutase, uridine diphosphogalactopyranose, TcUGM, UDP galactopyranose mutase, UDP-D-galactopyranose mutase, UDP-Gal mutase, UDP-galactopyranose mutase, UDP-Galp mutase, UGM, UgmA, UNGM, uridine 5'-diphosphate galactopyranose mutase, uridine 5'-diphosphate galactopyranosemutase, uridine 5'-diphosphate-galactopyranose mutase, uridine diphosphate galactopyranose mutase
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General Information
General Information on EC 5.4.99.9 - UDP-galactopyranose mutase
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evolution
malfunction
physiological function
additional information
conserved active site residues in Aspegillus fumigatus UGM compared to prokaryotic UGMs, overview
evolution
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substrate recognition of bacterial and eukaryotic enzyme, involving a dynamic Arg, conserved steric interactions, and enzyme-substrate noncovalent interactions, overview. Domain 1 is important for positioning Galp for nucleophilic attack, domain 2 provides most of the interactions with the uridine group, and domain 3 figures prominently in binding the diphosphate
evolution
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substrate recognition of bacterial and eukaryotic enzyme, involving a dynamic Arg, conserved steric interactions, and enzyme-substrate noncovalent interactions, overview. Domain 1 is important for positioning Galp for nucleophilic attack, domain 2 provides most of the interactions with the uridine group, and domain 3 figures prominently in binding the diphosphate
evolution
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substrate recognition of bacterial and eukaryotic enzyme, involving a dynamic Arg, conserved steric interactions, and enzyme-substrate noncovalent interactions, overview. Domain 1 is important for positioning Galp for nucleophilic attack, domain 2 provides most of the interactions with the uridine group, and domain 3 figures prominently in binding the diphosphate
evolution
-
substrate recognition of bacterial and eukaryotic enzyme, involving a dynamic Arg, conserved steric interactions, and enzyme-substrate noncovalent interactions, overview. Domain 1 is important for positioning Galp for nucleophilic attack, domain 2 provides most of the interactions with the uridine group, and domain 3 figures prominently in binding the diphosphate
evolution
-
substrate recognition of bacterial and eukaryotic enzyme, involving a dynamic Arg, conserved steric interactions, and enzyme-substrate noncovalent interactions, overview. Domain 1 is important for positioning Galp for nucleophilic attack, domain 2 provides most of the interactions with the uridine group, and domain 3 figures prominently in binding the diphosphate
evolution
-
substrate recognition of bacterial and eukaryotic enzyme, involving a dynamic Arg, conserved steric interactions, and enzyme-substrate noncovalent interactions, overview. Domain 1 is important for positioning Galp for nucleophilic attack, domain 2 provides most of the interactions with the uridine group, and domain 3 figures prominently in binding the diphosphate
evolution
-
substrate recognition of bacterial and eukaryotic enzyme, involving a dynamic Arg, conserved steric interactions, and enzyme-substrate noncovalent interactions, overview. Domain 1 is important for positioning Galp for nucleophilic attack, domain 2 provides most of the interactions with the uridine group, and domain 3 figures prominently in binding the diphosphate
evolution
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substrate recognition of bacterial and eukaryotic enzyme, involving a dynamic Arg, conserved steric interactions, and enzyme-substrate noncovalent interactions, overview. Domain 1 is important for positioning Galp for nucleophilic attack, domain 2 provides most of the interactions with the uridine group, and domain 3 figures prominently in binding the diphosphate
evolution
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substrate recognition of bacterial and eukaryotic enzyme, involving a dynamic Arg, conserved steric interactions, and enzyme-substrate noncovalent interactions, overview. Domain 1 is important for positioning Galp for nucleophilic attack, domain 2 provides most of the interactions with the uridine group, and domain 3 figures prominently in binding the pyrophosphate
evolution
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all organisms that generate Galf-containing glycans encode a UGM homologue
evolution
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all organisms that generate Galf-containing glycans encode a UGM homologue
evolution
all organisms that generate Galf-containing glycans encode a UGM homologue
evolution
all organisms that generate Galf-containing glycans encode a UGM homologue
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
evolution
Deinococcus radiodurans R1 / ATCC 13939 / DSM 20539
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substrate recognition of bacterial and eukaryotic enzyme, involving a dynamic Arg, conserved steric interactions, and enzyme-substrate noncovalent interactions, overview. Domain 1 is important for positioning Galp for nucleophilic attack, domain 2 provides most of the interactions with the uridine group, and domain 3 figures prominently in binding the diphosphate
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glf-1 mutants display significant late embryonic and larval lethality, and other phenotypes indicative of defective surface coat synthesis, the glycan-rich outermost layer of the nematode cuticle
malfunction
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Aspergillus nidulans strains deleted for UgmA lack immunolocalizable UDP-D-galactofuranose, have growth and sporulation defects, abnormal wall architecture, and significantly larger hyphal surface subunits and lower cell wall viscoelastic moduli
malfunction
AfUgmA residues R182 and R327 are important for its function in vivo, with even conservative amino (RK) substitutions producing AnugmADELTA-phenotype strains. Loss of cell wall alpha-D-galactofuranose is associated with increased hyphal surface adhesion. AfUgmA active site mutations do not affect UgmA-GFP cytoplasmic distribution. Mutant phenotypes, overview
malfunction
deletion or repression of Aspergillus nidulans gene ugmA (AnugmA), involved in galactofuranose biosynthesis, impairs growth and increases sensitivity to caspofungin, a beta-1,3-glucan synthesis antagonist. Alteration in galactofuranose affects wall glucan composition in Aspergillus nidulans. Wild-type and complemented wild-type hyphal walls have relatively low alpha-glucan content compared to mutant and AnugmADELTA strains. Mutant phenotypes, overview
malfunction
kinetic parameters for the reduction of AfUGM mutant enzymes by NADPH compared to wild-type enzyme, overview. The active site mutants show high losses of catalytic efficiency compared to the wild-type
malfunction
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the active site mutant shows high losses of catalytic efficiency compared to the wild-type enzyme
malfunction
the active site mutants show high losses of catalytic efficiency compared to the wild-type
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
malfunction
Aspergillus nidulans FGSC A4 / ATCC 38163 / CBS 112.46 / NRRL 194 / M139
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deletion or repression of Aspergillus nidulans gene ugmA (AnugmA), involved in galactofuranose biosynthesis, impairs growth and increases sensitivity to caspofungin, a beta-1,3-glucan synthesis antagonist. Alteration in galactofuranose affects wall glucan composition in Aspergillus nidulans. Wild-type and complemented wild-type hyphal walls have relatively low alpha-glucan content compared to mutant and AnugmADELTA strains. Mutant phenotypes, overview
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malfunction
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glf-1 mutants display significant late embryonic and larval lethality, and other phenotypes indicative of defective surface coat synthesis, the glycan-rich outermost layer of the nematode cuticle
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glf-1 is required for normal post-embryonic development
physiological function
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UDP-galactopyranose mutase is a virulence factor in Leishmania major
physiological function
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UgmA is important for cell wall surface subunit organization and wall viscoelasticity
physiological function
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the enzyme is involved in the biosynthesis of capsular polysaccharides in Campylobacter jejuni 11168. These capsular polysaccharides are known virulence factors that are required for adhesion and invasion of human epithelial cells. Production of suitable quantities of the sugar nucleotide substrate required for the assembly of a capsular polysaccharide containing N-acetyl-alpha-D-galactofuranose, which is essential for viability
physiological function
the enzyme is involved in the synthesis of the cell wall
physiological function
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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
physiological function
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UDP-galactopyranose mutase catalyzes the isomerization of UDP-galactopyranose to UDP-galactofuranose, the biosynthetic precursor of galactofuranose residues, which are essential components of the cell wall and play an important role in Aspergillus fumigatus virulence
physiological function
galactofuranose (Galf) biosynthesis begins with the conversion of UDP-galactopyranose (UDP-Galp) to UDP-Galf as a rate-limiting step catalyzed by the flavoenzyme UDP-galactopyranose mutase (UGM). Enzyme UGM is essential for the survival and proliferation of several pathogens. UGM from the pathogenic fungus Aspergillus fumigatus also catalyzes the isomerization of UDP-arabinopyranose (UDP-Arap), which differs from UDPGalp by lacking a -CH2-OH substituent at the C5 position of the hexose ring
physiological function
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the enzyme catalyzes the formation of UDP-galactofuranose (UDP-Galf), which is required to produce Galf-containing glycoconjugates
physiological function
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the enzyme catalyzes the formation of UDP-galactofuranose (UDP-Galf), which is required to produce Galf-containing glycoconjugates
physiological function
the enzyme catalyzes the formation of UDP-galactofuranose (UDP-Galf), which is required to produce Galf-containing glycoconjugates
physiological function
the enzyme catalyzes the formation of UDP-galactofuranose (UDP-Galf), which is required to produce Galf-containing glycoconjugates
physiological function
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the enzyme UDP-galactopyranose mutase (UGM) catalyses the conversion of galactopyranose into galactofuranose. It is critical for the survival and proliferation of several pathogenic agents, both prokaryotic and eukaryotic
physiological function
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UDP-alpha-D-galactopyranose (UDP-Galp) is a precursor of galactofuranose (Galf), which is a primary component of the cell-wall glycans of several microorganisms. The interconversion of UDP-Galp and UDP-Galf is catalyzed by UDP galactopyranose mutase (UGM)
physiological function
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UDP-galactopyranose mutase (UGM) catalyzes the interconversion between UDP-galactopyranose and UDPgalactofuranose. Galactofuranose is found in bacterial and fungal cell walls and is a cell surface virulence factor in protozoan parasites. UGMs are active only in the reduced form
physiological function
UDP-galactopyranose mutase (UGM) catalyzes the interconversion between UDP-galactopyranose and UDPgalactofuranose. Galactofuranose is found in bacterial and fungal cell walls and is a cell surface virulence factor in protozoan parasites. UGMs are active only in the reduced form
physiological function
UDP-galactopyranose mutase (UGM) catalyzes the interconversion between UDP-galactopyranose and UDPgalactofuranose. Galactofuranose is found in bacterial and fungal cell walls and is a cell surface virulence factor in protozoan parasites. UGMs are active only in the reduced form
physiological function
UDP-galactopyranose mutase (UGM) is a flavin-containing enzyme that catalyzes the reversible conversion of UDP-galactopyranose (UDP-Galp) to UDP-galactofuranose (UDP-Galf) and plays a key role in the biosynthesis of the mycobacterial cell wall galactofuran. Substrate binding induces local changes in MtUGM active site
physiological function
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UDP-galactopyranose mutase (UGM) is a key enzyme in the biosynthesis of mycobacterial cell walls. Galactofuranose (Galf) is an essential building block of the galactan chains in the cell walls of mycobacteria
physiological function
UDP-galactopyranose mutase (UGM) plays an essential role in galactofuranose biosynthesis in pathogens by catalyzing the conversion of UDP-galactopyranose to UDP-galactofuranose
physiological function
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UDP-galactopyranose mutase (UGM), an enzyme found in many eukaryotic and prokaryotic human pathogens, catalyzes the interconversion of UDP-galactopyranose (UDP-Galp) and UDPgalactofuranose (UDP-Galf), the latter being used as the biosynthetic precursor of the galactofuranose polymer portion of the mycobacterium cell wall
physiological function
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glf-1 is required for normal post-embryonic development
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physiological function
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the enzyme is involved in the biosynthesis of capsular polysaccharides in Campylobacter jejuni 11168. These capsular polysaccharides are known virulence factors that are required for adhesion and invasion of human epithelial cells. Production of suitable quantities of the sugar nucleotide substrate required for the assembly of a capsular polysaccharide containing N-acetyl-alpha-D-galactofuranose, which is essential for viability
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Arg182 and Arg327 play important roles in stabilizing the position of the diphosphates of the nucleotide sugar and help to facilitate the positioning of the galactose moiety for catalysis. Substrate recognition and structural changes observed upon substrate binding involving the mobile loops and the critical arginine residues Arg182 and Arg327, overview. The Aspergillus fumigatus enzyme contains a third flexible loop (loop III) above the si-face of the isoalloxazine ring that changes position depending on the redox state of the flavin cofactor
additional information
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Arg182 and Arg327 play important roles in stabilizing the position of the diphosphates of the nucleotide sugar and help to facilitate the positioning of the galactose moiety for catalysis. Substrate recognition and structural changes observed upon substrate binding involving the mobile loops and the critical arginine residues Arg182 and Arg327, overview. The Aspergillus fumigatus enzyme contains a third flexible loop (loop III) above the si-face of the isoalloxazine ring that changes position depending on the redox state of the flavin cofactor
additional information
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enzyme-substrate binding analysis by combination of UV/visible spectroscopy, X-ray crystallography, saturation transfer difference NMR spectroscopy, molecular dynamics, and CORCEMA-ST calculations. Two arginines in the enzyme, Arg59 and Arg168, play critical roles in the catalytic mechanism of the enzyme and in controlling its specificity to ultimately lead to an N-acetyl-alpha-D-galactofuranose-containing capsular polysaccharides. Substrate-recognition patterns compared to the Eschericia coli enzyme, overview
additional information
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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
additional information
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molecular dynamics studies of active site flexibility, overview
additional information
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molecular dynamics studies of active site flexibility, overview
additional information
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molecular dynamics studies of active site flexibility, overview
additional information
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molecular dynamics studies of active site flexibility, overview
additional information
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molecular dynamics studies of active site flexibility, overview
additional information
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molecular dynamics studies of active site flexibility, overview
additional information
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molecular dynamics studies of active site flexibility, overview
additional information
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substrate recognition mechanism, overview. Molecular dynamics studies of active site flexibility, overview
additional information
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substrate recognition mechanism, overview. Molecular dynamics studies of active site flexibility, overview
additional information
active site structure, the citrate ion forms salt bridges with UGM residues R288 and H290 and numerous ordered water molecules, thereby participating in a hydrogen-bonding network with the active site residues. A strong density feature is observed bridging the citrate ion and the oxidized FAD
additional information
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active site structure, the citrate ion forms salt bridges with UGM residues R288 and H290 and numerous ordered water molecules, thereby participating in a hydrogen-bonding network with the active site residues. A strong density feature is observed bridging the citrate ion and the oxidized FAD
additional information
AfUgmA residues R182 and R327 are important for its function in vivo, with even conservative amino (RK) substitutions producing AnugmADELTA phenotype strains
additional information
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AfUgmA residues R182 and R327 are important for its function in vivo, with even conservative amino (RK) substitutions producing AnugmADELTA phenotype strains
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
additional information
molecular dynamics simulations. Binding modes of substrates in the active site of enzyme AfUGM
additional information
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molecular dynamics simulations. Binding modes of substrates in the active site of enzyme AfUGM
additional information
residues F66, Y104, Q107, N207, and Y317 are important for promoting the transition state conformation for UDP-galactofuranose formation. The active site residues are conserved in eukaryotic UGMs but are absent or different in bacterial UGMs
additional information
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residues F66, Y104, Q107, N207, and Y317 are important for promoting the transition state conformation for UDP-galactofuranose formation. The active site residues are conserved in eukaryotic UGMs but are absent or different in bacterial UGMs
additional information
residues H66, Y100, Q103, N201, and Y317 are important for promoting the transition state conformation for UDP-galactofuranose formation. The active site residues are conserved in eukaryotic UGMs but are absent or different in bacterial UGMs
additional information
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residues H66, Y100, Q103, N201, and Y317 are important for promoting the transition state conformation for UDP-galactofuranose formation. The active site residues are conserved in eukaryotic UGMs but are absent or different in bacterial UGMs
additional information
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residues H68 is important for promoting the transition state conformation for UDP-galactofuranose formation
additional information
structure analysis reveals UDP bound in the active site and galactopyranose linked to the FAD through a covalent bond between the anomeric C of galactopyranose and N5 of the FAD. The structure confirms the role of the flavin as nucleophile and supports the hypothesis that the proton destined for O5 of galactofuranose is shuttled from N5 of the FAD via O4 of the FAD. His63 is part of the conserved histidine loop, which has the sequence GGHVIF in AfUGM. All UGMs have Gly and His at positions 1 and 3 of the loop, respectively. The conformation of the His loop of AfUGM depends on the redox state of the flavin. The protein-flavin interactions are thought be essential for maintaining the active conformation of UGM
additional information
Deinococcus radiodurans R1 / ATCC 13939 / DSM 20539
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substrate recognition mechanism, overview. Molecular dynamics studies of active site flexibility, overview
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additional information
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enzyme-substrate binding analysis by combination of UV/visible spectroscopy, X-ray crystallography, saturation transfer difference NMR spectroscopy, molecular dynamics, and CORCEMA-ST calculations. Two arginines in the enzyme, Arg59 and Arg168, play critical roles in the catalytic mechanism of the enzyme and in controlling its specificity to ultimately lead to an N-acetyl-alpha-D-galactofuranose-containing capsular polysaccharides. Substrate-recognition patterns compared to the Eschericia coli enzyme, overview
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