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Information on EC 1.1.1.132 - GDP-mannose 6-dehydrogenase and Organism(s) Pseudomonas aeruginosa and UniProt Accession P11759
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1.1.1.132 GDP-mannose 6-dehydrogenaseIUBMB Comments
Also acts on the corresponding deoxynucleoside diphosphate derivative as a substrate.
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Word Map
- 1.1.1.132
- aeruginosa
- alginate
-
cystic
- fibrosis
- mucoid
-
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
The taxonomic range for the selected organisms is: Pseudomonas aeruginosa
The expected taxonomic range for this enzyme is: Bacteria, Eukaryota, Archaea
The expected taxonomic range for this enzyme is: Bacteria, Eukaryota, Archaea
Synonyms
guanosine diphospho-d-mannose dehydrogenase, gdp mannose dehydrogenase, gdp-d-mannose dehydrogenase, gdp-mannose 6-dehydrogenase, guanosine diphosphate mannose dehydrogenase, 
more
topSYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
GDP mannose dehydrogenase
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-
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GMD
guanosine diphospho-D-mannose dehydrogenase
guanosine diphosphomannose dehydrogenase
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GMD
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-
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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+
class of 4-electron transfer dehydrogenases
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REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
redox reaction
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-
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oxidation
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reduction
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PATHWAY SOURCE
PATHWAYS
BRENDA
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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.
CAS REGISTRY NUMBER
COMMENTARY
37250-63-8
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SUBSTRATE
PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
GDP-D-mannose + 2 NAD+ + H2O
GDP-D-mannuronate + 2 NADH + 2 H+
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-
-
?
GDP-D-mannose + NAD+ + H2O
GDP-D-mannunorate + NADH
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the enzyme catalyzes the first committed step in alginate biosynthesis
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-
?
additional information
?
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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
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-
?
additional information
?
-
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
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?
additional information
?
-
-
key enzyme in alginate biosynthesis
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-
?
additional information
?
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no substrate: D-mannose, UDP-D-mannose, UDP-D-glucose, TDP-D-glucose, CDP-D-glucose
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-
?
NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
GDP-D-mannose + NAD+ + H2O
GDP-D-mannunorate + NADH
-
the enzyme catalyzes the first committed step in alginate biosynthesis
-
-
?
additional information
?
-
-
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
-
-
?
additional information
?
-
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
-
-
?
additional information
?
-
-
key enzyme in alginate biosynthesis
-
-
?
COFACTOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
NAD+
-
-
NAD+
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cooperative behaviour with respect to NAD+ binding, sensitive to pH
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
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
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
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 within 5 min, complete reactivation by dithiothreitol
additional information
-
full reactivation by dithiothreitol (25 mM) after p-hydroxymercuribenzoate or iodoacetamide inactivation
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additional information
-
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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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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Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
additional information
additional information
-
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
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
0.0009
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
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
PDB
SCOP
CATH
UNIPROT
ORGANISM
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
48000
48000
-
SDS-PAGE, Escherichia coli and Pseudomonas aeruginosa expressed polypeptide
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
hexamer
additional information
additional information
forms a domain-swapped dimer with two polypeptide chains contributing to each active site, crystallization data
additional information
-
peptide mapping of recombinant wild-type and mutant enzymes with MALDI-TOF mass spectrometry
CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
C213A
-
site-directed mutagenesis, 1.8fold increased Vmax compared to the wild-type enzyme
C268A
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site-directed mutagenesis, 250fold reduced Vmax, 5fold increased KM, and reduced sensitivity to penicillic acid inactivation compared to the wild-type enzyme
TEMPERATURE STABILITY
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
GENERAL STABILITY
ORGANISM
UNIPROT
LITERATURE
STORAGE STABILITY
ORGANISM
UNIPROT
LITERATURE
-70°C, 1-3 mg/ml purified protein, 50 mM triethanolamine acetate, pH 7.6, 1 mM DTT
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PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
pH/heat treatment acetone precipitation HPLC gel filtration chromatography
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protamine sulfate precipitation, gel exclusion, ion exchange chromatography
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recombinant wild-type and mutant enzymes from Escherichia coli by gel filtration of enzyme with tightly bound GDP-mannuronic acid and NAD+, dialysis and ion exchange chromatography
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CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
gene algD, overexpression of wild-type and mutant enzymes in Escherichia coli
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RENATURED/Commentary
ORGANISM
UNIPROT
LITERATURE
inactivation by iodacetamide or p-hydroxymercuribenzoate is completely reversible
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REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Roychoudhury, S.; Mmay, T.B.; Gill, J.F.; Singh, S.K.; Feingold, D.S.; Chakrabarty, A.M.
Purification and characterization of guanosine diphospho-D-mannose dehydrogenase. A key enzyme in the biosynthesis of alginate by Pseudomonas aeruginosa
J. Biol. Chem.
264
9380-9385
1989
Pseudomonas aeruginosa
Pugashetti, B.K.; Vadas, L.; Prihar, H.S.; Feingold, D.S.
GDPmannose dehydrogenase and biosynthesis of alginate-like polysaccharide in a mucoid strain of Pseudomonas aeruginosa
J. Bacteriol.
153
1107-1110
1983
Pseudomonas aeruginosa
Deretic, V.; Gill, J.F.; Chakrabarty, A.M.
Gene algD coding for GDPmannose dehydrogenase is transcriptionally activated in mucoid Pseudomonas aeruginosa
J. Bacteriol.
169
351-358
1987
Pseudomonas aeruginosa
Tavares, I.M.; Leitao, J.H.; Fialho, A.M.; Sa-Correia, I.
Pattern of changes in the activity of enzymes of GDP-D-mannuronic acid synthesis and in the level of transcription of algA, algC and algD genes accompanying the loss and emergence of mucoidy in Pseudomonas aeruginosa
Res. Microbiol.
150
105-116
1999
Pseudomonas aeruginosa
Martins, L.O.; Sa-Correia, I.
Alginate biosynthesis in mucoid recombinants of Pseudomonas aeruginosa overproducing GDP-mannose dehydrogenase
Enzyme Microb. Technol.
13
385-389
1991
Pseudomonas aeruginosa
Tatnell, P.J.; Russell, N.J.; Gacesa, P.
Overexpression of the GDP-mannose dehydrogenase gene from Pseudomonas aeruginosa
Biochem. Soc. Trans.
24
405S
1996
Pseudomonas aeruginosa
Elloumi, N.; Moreau, B.; Aguiar, L.; Jaziri, N.; Sauvage, M.; Hulen, C.; Capmau, M.L.
Inhibitors of GDP-mannose dehydrogenase of Pseudomonas aeruginosa mucoid strains
Eur. J. Med. Chem.
27
149-154
1992
Pseudomonas aeruginosa
-
Roychoudhury, S.; Chakrabarty, K.; Ho, Y.K.; Chakrabarty, A.M.
Characterization of guanosine diphospho-D-mannose dehydrogenase from Pseudomonas aeruginosa. Structural analysis by limited proteolyses
J. Biol. Chem.
267
990-996
1992
Pseudomonas aeruginosa
Mitsuya, Y.; Kawai, S.; Kobayashi, H.
Influence of macrolides on guanosine diphospho-D-mannose dehydrogenase activity in Pseudomonas biofilm
J. Infect. Chemother.
6
45-50
2000
Pseudomonas aeruginosa
Tatnell, P.J.; Russell, N.J.; Gacesa, P.
GDP-mannose dehydrogenase is the key regulatory enzyme in alginate biosynthesis in Pseudomonas aeruginosa: evidence from metabolite studies
Microbiology
140
1745-1754
1994
Pseudomonas aeruginosa
Naught, L.E.; Gilbert, S.; Imhoff, R.; Snook, C.; Beamer, L.; Tipton, P.
Allosterism and cooperativity in Pseudomonas aeruginosa GDP-mannose dehydrogenase
Biochemistry
41
9637-9645
2002
Pseudomonas aeruginosa
Snook, C.F.; Tipton, P.A.; Beamer, L.J.
Crystal structure of GDP-mannose dehydrogenase: a key enzyme of alginate biosynthesis in P. aeruginosa
Biochemistry
42
4658-4668
2003
Pseudomonas aeruginosa (P11759)
Kimmel, J.L.; Tipton, P.A.
Inactivation of GDP-mannose dehydrogenase from Pseudomonas aeruginosa by penicillic acid identifies a critical active site loop
Arch. Biochem. Biophys.
441
132-140
2005
Pseudomonas aeruginosa
Li, F.; Yu, J.; Yang, H.; Wan, Z.; Bai, D.
Effects of ambroxol on alginate of mature Pseudomonas aeruginosa biofilms
Curr. Microbiol.
57
1-7
2008
Pseudomonas aeruginosa, Pseudomonas aeruginosa (P11759)
Beswick, L.; Dimitriou, E.; Ahmadipour, S.; Zafar, A.; Rejzek, M.; Reynisson, J.; Field, R.A.; Miller, G.J.
Inhibition of the GDP-D-mannose dehydrogenase from Pseudomonas aeruginosa using targeted sugar nucleotide probes
ACS Chem. Biol.
15
3086-3092
2020
Pseudomonas aeruginosa (P11759), Pseudomonas aeruginosa, Pseudomonas aeruginosa ATCC 15692 (P11759)
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