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Information on EC 1.1.1.132 - GDP-mannose 6-dehydrogenase
for references in articles please use BRENDA:EC1.1.1.132
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EC Tree 1 Oxidoreductases
1.1 Acting on the CH-OH group of donors
1.1.1 With NAD+ or NADP+ as acceptor
1.1.1.132 GDP-mannose 6-dehydrogenase
IUBMB Comments
Also acts on the corresponding deoxynucleoside diphosphate derivative as a substrate.
The expected taxonomic range for this enzyme is: Bacteria, Eukaryota, Archaea
- 1.1.1.132
- aeruginosa
- alginate
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cystic
- fibrosis
- mucoid
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mannuronic
- midecamycin
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sputum
- vinelandii
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molecular-genetic
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azotobacter
- erythromycin
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macrolide
- elastase
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chemoenzymatic
- gdpmannose
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multidrug-resistant
Synonyms
guanosine diphospho-d-mannose dehydrogenase, gdp mannose dehydrogenase, gdp-d-mannose dehydrogenase, gdp-mannose 6-dehydrogenase, guanosine diphosphate mannose dehydrogenase, more
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SYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
GDP mannose dehydrogenase
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GDP-D-mannose dehydrogenase
GDP-mannose dehydrogenase
GMD
guanosine diphosphate mannose dehydrogenase
guanosine diphospho-D-mannose dehydrogenase
guanosine diphosphomannose dehydrogenase
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GMD
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guanosine diphospho-D-mannose dehydrogenase
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REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
GDP-D-mannose + 2 NAD+ + H2O = GDP-D-mannuronate + 2 NADH + 2 H+
also acts on the corresponding deoxynucleoside diphosphate derivative as a substrate
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GDP-D-mannose + 2 NAD+ + H2O = GDP-D-mannuronate + 2 NADH + 2 H+
class of 4-electron transfer dehydrogenases
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REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
oxidation
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redox reaction
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reduction
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PATHWAY SOURCE
PATHWAYS
BRENDA
MetaCyc
alginate biosynthesis I (algal), alginate biosynthesis II (bacterial)
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SYSTEMATIC NAME
IUBMB Comments
GDP-D-mannose:NAD+ 6-oxidoreductase
Also acts on the corresponding deoxynucleoside diphosphate derivative as a substrate.
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CAS REGISTRY NUMBER
COMMENTARY
37250-63-8
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SUBSTRATE
PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
LITERATURE
COMMENTARY
Reversibility
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
GDP-D-mannose + NAD+ + H2O
GDP-D-mannuronate + NADH + H+
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Substrates: -
Products: -
Products: -
?
Deoxy-GDP-D-mannose + 2 NAD+ + H2O
deoxy-GDP-D-mannuronate + 2 NADH + 2 H+
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Substrates: -
Products: -
Products: -
r
Deoxy-GDP-D-mannose + 2 NAD+ + H2O
deoxy-GDP-D-mannuronate + 2 NADH + 2 H+
Arthrobacter sp. NRRL B1973
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Substrates: -
Products: -
Products: -
r
deoxy-GDP-D-mannose + NAD+ + H2O
deoxy-GDP-D-mannuronate + NADH
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Substrates: -
Products: -
Products: -
?
deoxy-GDP-D-mannose + NAD+ + H2O
deoxy-GDP-D-mannuronate + NADH
Arthrobacter sp. NRRL B1973
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Substrates: -
Products: -
Products: -
?
GDP-D-mannose + 2 NAD+ + H2O
GDP-D-mannuronate + 2 NADH + 2 H+
Substrates: -
Products: -
Products: -
?
GDP-D-mannose + 2 NAD+ + H2O
GDP-D-mannuronate + 2 NADH + 2 H+
Substrates: -
Products: -
Products: -
?
GDP-D-mannose + NAD+ + H2O
GDP-D-mannunorate + NADH
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Substrates: -
Products: -
Products: -
?
GDP-D-mannose + NAD+ + H2O
GDP-D-mannunorate + NADH
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Substrates: the enzyme catalyzes the first committed step in alginate biosynthesis
Products: -
Products: -
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GDP-D-mannose + NAD+ + H2O
GDP-D-mannuronate + NADH
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Substrates: -
Products: -
Products: -
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GDP-D-mannose + NAD+ + H2O
GDP-D-mannuronate + NADH
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Substrates: -
Products: -
Products: -
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GDP-mannose + NAD+ + H2O
GDP-mannuronate + NADH
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Substrates: -
Products: -
Products: -
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GDP-mannose + NAD+ + H2O
GDP-mannuronate + NADH
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Substrates: -
Products: -
Products: -
ir
GDP-mannose + NAD+ + H2O
GDP-mannuronate + NADH
Arthrobacter sp. NRRL B1973
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Substrates: -
Products: -
Products: -
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GDP-mannose + NAD+ + H2O
GDP-mannuronate + NADH
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Substrates: -
Products: -
Products: -
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GDP-mannose + NAD+ + H2O
GDP-mannuronate + NADH
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Substrates: -
Products: water-soluble and insoluble polysaccharides are produced, containing glucuronic and mannuronic acid, glucose and rhamnose, GDP-D-mannose dehydrogenase activity detected in 30 h cultures and 36 h cultures containing only water-insoluble capsular or water-soluble polysaccharides, respectively
Products: water-soluble and insoluble polysaccharides are produced, containing glucuronic and mannuronic acid, glucose and rhamnose, GDP-D-mannose dehydrogenase activity detected in 30 h cultures and 36 h cultures containing only water-insoluble capsular or water-soluble polysaccharides, respectively
?
GDP-mannose + NAD+ + H2O
GDP-mannuronate + NADH
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Substrates: -
Products: -
Products: -
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GDP-mannose + NAD+ + H2O
GDP-mannuronate + NADH
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Substrates: -
Products: -
Products: -
ir
additional information
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Substrates: key enzyme in alginate biosynthesis
Products: -
Products: -
?
additional information
?
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Substrates: no substrate: D-mannose, UDP-D-mannose, UDP-D-glucose, TDP-D-glucose, CDP-D-glucose
Products: -
Products: -
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additional information
?
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Substrates: GMD is the key enzyme in alginate biosynthesis. Biofilm-forming bacteria Pseudomonas aeruginosa is a common pathogen in mechanically ventilated newborns, which can cause life-threatening infections
Products: -
Products: -
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additional information
?
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Substrates: GMD is the key enzyme in alginate biosynthesis. Biofilm-forming bacteria Pseudomonas aeruginosa is a common pathogen in mechanically ventilated newborns, which can cause life-threatening infections
Products: -
Products: -
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additional information
?
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Substrates: algD is localized in an alginate biosynthesis cluster
Products: -
Products: -
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NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
LITERATURE
COMMENTARY
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
GDP-D-mannose + NAD+ + H2O
GDP-D-mannunorate + NADH
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Substrates: the enzyme catalyzes the first committed step in alginate biosynthesis
Products: -
Products: -
?
GDP-D-mannose + NAD+ + H2O
GDP-D-mannuronate + NADH + H+
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Substrates: -
Products: -
Products: -
?
additional information
?
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Substrates: key enzyme in alginate biosynthesis
Products: -
Products: -
?
additional information
?
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Substrates: GMD is the key enzyme in alginate biosynthesis. Biofilm-forming bacteria Pseudomonas aeruginosa is a common pathogen in mechanically ventilated newborns, which can cause life-threatening infections
Products: -
Products: -
?
additional information
?
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Substrates: GMD is the key enzyme in alginate biosynthesis. Biofilm-forming bacteria Pseudomonas aeruginosa is a common pathogen in mechanically ventilated newborns, which can cause life-threatening infections
Products: -
Products: -
?
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COFACTOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
NAD+
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NAD+
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cooperative behaviour with respect to NAD+ binding, sensitive to pH
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METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Mg2+
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133.79% activity of isoform GMD1 at 1 mM, 120.25% activity of isoform GMD2 at 1 mM
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INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
5'-(3-hydroxypropyl)-amino-5'-deoxy-guanosine
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only after preincubation with enzyme
5'-azido-5'-deoxy-N2-2',3'-O-triacetylguanosine
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only after preincubation with enzyme
5'[[[[(2'',3'',4'',6''-tetra-O-acetyl 6''-ethynyl)alpha-D-mannopyranosyl oxy]-carbonyl]amino]sulfonyl]-2',3'-isopropylidene N2-acetyl guanosine
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GDP-analog, 0.1 mM, 60% inhibition
ambroxol
i.e. 2-amino-3,5-dibromo-N-[trans-4-hydroxycyclohexyl]benzylamine, inhibits GMD activity, reduces the production of alginate, the expression of the important genes, and affects the structure of mucoid Pseudomonas aeruginosa biofilms, overview; reduces activity of the key enzyme GMD in alginate biosynthesis in a concentration-dependent manner
erythromycin
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potent dose-dependent inhibitory effect, inhibition of biofilm formation, PT-1578
iodacetamide
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40% inactivation within 30 min, complete reactivation by dithiothreitol
N2-acetyl-2',3'-isopropylidene guanosine
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only after preincubation with enzyme
N2-acetyl-5'-amino-5'-deoxy-2',3'-O-acetylguanosine
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only after preincubation with enzyme
N2-acetyl-5'-amino-5'-deoxy-guanosine
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only after preincubation with enzyme
p-hydroxymercuribenzoate
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96% inactivation after 5 min preincubation; 96% inactivation within 5 min, complete reactivation by dithiothreitol
Zn2+
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potent inhibitor with 0.75% residual activity at 1 mM for both isoforms GMD1 and GMD2
additional information
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full reactivation by dithiothreitol (25 mM) after p-hydroxymercuribenzoate or iodoacetamide inactivation
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additional information
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strains which resist 0.005 mg/ml of tobramycin treated by 5'-(3-hydroxypropyl)-amino-5'-deoxy-guanosine, tetra-O-acetylmannopyranose and 5'[[[[(2'',3'',4'',6''-tetra-O-acetyl 6''-ethynyl)alpha-D-mannopyranosyl oxy]-carbonyl]amino]sulfonyl]-2',3'-isopropylidene N2-acetyl guanosine recover 20, 75 and 85% of their sensisivity towards tobramycin
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DISEASE
TITLE OF PUBLICATION
LINK TO PUBMED
Cystic Fibrosis
GDPmannose dehydrogenase and biosynthesis of alginate-like polysaccharide in a mucoid strain of Pseudomonas aeruginosa.
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KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
additional information
additional information
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in phosphate buffer, enzyme shows Michaelis-Menten kinetics, in Tris buffer, enzyme shows marked cooperativity with respect to NAD+ binding. Phosphate and GMP are allosteric effectors
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0.095
GDP-D-mannose
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pH and temperature not specified in the publication
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Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
additional information
additional information
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inactivation kinetics of recombinant wild-type and mutant enzymes with penicillic acid
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IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
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SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
0.0009
0.002
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inorganic phosphate limitation, 85 h after changing carbon source from sorbitol to sucrose
0.002 - 0.015
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mucoid forms, activity correlated with alginate production and level of transcription of algD gene
additional information
additional information
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increase of activity has only limited effect on the stimulation of alginate synthesis, existance of other rate-limiting enzymatic step suggested
additional information
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presence of 1 mM GDP-mannose, GDP-glucose, GMP, GDP, GTP or cGMP retards tryptic digest of enzyme and protects subsequent loss of enzyme activity, amino-terminal domain contains substrate and cofactor binding sites, carboxy-terminal domain is essential for catalytic activity
additional information
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higher enzyme activities after IPTG induction only for pPT3 containing strains, low GDP-mannuronate production with pMMB66EH only detectable in mucoid strains, higher with pPT3 with increase in cells of mucoid and non-mucoid strains with IPTG, alginate formation occurs only in mucoid strains without significant increase with IPTG, later enzyme of alginate biosynthesis suggested to become rate-limiting
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pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
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pH RANGE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
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TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
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pI VALUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
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ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
NCIB 8789, water soluble polysaccharide producing strains E, W and O
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brenda
SM52B, mutant of A. vinelandii NCIB 9068, alginate-prducing ability, no activity with sorbitol as sole carbon source during batch growth, enzyme not produced, loss of ability to synthesise alginate during prolonged continuous culture after 300 h for mutant and more than 1000 h for parent strain, ability transferable by conjugation
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brenda
algD gene overproduced in strain 8822 using a plasmid vector containing algD under control of the tac promoter
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brenda
enzyme overproduced using 3 different plasmid vectors containing algD under control of the tac promoter expressed in non-mucoid strain PAO1 and mucoid strain PAO568, pPT3 and pPT4 are forward and reverse clones contain leader sequence with possible transcriptional/translational regulatory sequences of algD gene, no significant activity with pMMB66EH and pPT4 in either IPTG induced or non induced Escherichia coli, mucoid and non-mucoid Pseudomonas aeruginosa strains
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brenda
enzyme overproduced using a plasmid vector containing algD under control of the tac promoter
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brenda
mucoid clinical isolate PT-1578 and non-mucoid PAO1, very low activity of PAO1 regardless whether using nutrient-rich or poor medium, low activity with PT-1578 on enriched, increased on nutritionally poor medium
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brenda
mucoid strains of cystic fibrosis patients 8821 and its high-alginate-producing spontaneously variant 8821M, enzyme overproduced using 2 different plasmid vectors containing algD under control of the tac promoter mobilized into both strains
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brenda
mucoid strains of cystic fibrosis patients 8821, its high-alginate-producing spontaneously variant 8821M, IST23, IST27 and IST30, mucoid strains derived from the spontaneous nonmucoid strains during prolonged incubation under nutrient limitation in acetamide broth (Nm), rich in PolyP, no activity in spontaneous swiched nonmucoid variants (N) of initial isolated mucoid strains
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brenda
overexpression of tac promoter controlled algD gene containing different plasmids in mucoid strains FRD1 and PAO568 and non-mucoid strains FRD2 and PAO1
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brenda
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LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
Highest Expressing Human Cell Lines
Cell Line Links Show AA Sequence and Transmembrane Helices (1535 entries)
Please use the AA Sequence and Transmembrane Helices Search for a specific query.
Please use the AA Sequence and Transmembrane Helices Search for a specific query.
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PDB
SCOP
CATH
UNIPROT
ORGANISM
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MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
34000