| SMART accession number: | SM00984
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| Description: |
The UDP-glucose/GDP-mannose dehydrogenases are a small group of enzymes which possesses the ability to catalyse the NAD-dependent 2-fold oxidation of an alcohol to an acid without the release of an aldehyde intermediate (PUBMED:2470755), (PUBMED:9013585). |
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| Interpro abstract (IPR014027): |
The UDP-glucose/GDP-mannose dehydrogenases are a small group of enzymes which possesses the ability to catalyse the NAD-dependent 2-fold oxidation of an alcohol to an acid without the release of an aldehyde intermediate [(PUBMED:2470755), (PUBMED:9013585)]. The enzymes have a wide range of functions. In plants UDP-glucose dehydrogenase, EC 1.1.1.22, is an important enzyme in the synthesis of hemicellulose and pectin [(PUBMED:12031484)], which are the components of newly formed cell walls; while in zebrafish UDP-glucose dehydrogenase is required for cardiac valve formation [(PUBMED:11533493)]. In Xanthomonas campestris, a plant pathogen, UDP-glucose dehydrogenase is required for virulence [(PUBMED:11554764)]. GDP-mannose dehydrogenase, EC 1.1.1.132, catalyses the formation of GDP-mannuronic acid, which is the monomeric unit from which the exopolysaccharide alginate is formed. Alginate is secreted by a number of bacteria, which include Pseudomonas aeruginosa and Azotobacter vinelandii. In P. aeruginosa, alginate is believed to play an important role in the bacteria's resistance to antibiotics and the host immune response [(PUBMED:12135385)], while in A. vinelandii it is essential for the encystment process [(PUBMED:9864323)]. This entry represents the C-terminal substrate-binding domain of these enzymes. Structural studies indicate that this domain forms an incomplete dinucleotide binding fold [(PUBMED:10841783), (PUBMED:12705829)].
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| GO process: | oxidation-reduction process (GO:0055114) |
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| GO function: | NAD binding (GO:0051287), oxidoreductase activity, acting on the CH-OH group of donors, NAD or NADP as acceptor (GO:0016616) |
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| Family alignment: |
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Click on the following links for more information.
- Evolution (species in which this domain is found)
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- Cellular role (predicted cellular role)
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Cellular role: metabolism
- Literature (relevant references for this domain)
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Primary literature is listed below; Automatically-derived, secondary literature is also avaliable.
- Campbell RE, Sala RF, van de Rijn I, Tanner ME
- Properties and kinetic analysis of UDP-glucose dehydrogenase from group Astreptococci. Irreversible inhibition by UDP-chloroacetol.
- J Biol Chem. 1997; 272: 3416-22
- Display abstract
UDP-glucuronic acid is used by many pathogenic bacteria in theconstruction of an antiphagocytic capsule that is required for virulence.The enzyme UDP-glucose dehydrogenase catalyzes the NAD+-dependent 2-foldoxidation of UDP-glucose and provides a source of the acid. In the presentstudy the recombinant dehydrogenase from group A streptococci has beenpurified and found to be active as a monomer. The enzyme contains nochromophoric cofactors, and its activity is unaffected by the presence ofEDTA or carbonyl-trapping reagents. Initial velocity and productinhibition kinetic patterns are consistent with a bi-uni-uni-bi ping-pongmechanism in which UDP-glucose is bound first and UDP-glucuronate isreleased last. UDP-xylose was found to be a competitive inhibitor (Ki, 2.7microM) of the enzyme. The enzyme is irreversibly inactivated by uridine5'-diphosphate-chloroacetol due to the alkylation of an active sitecysteine thiol. The apparent second order rate constant for the inhibition(ki/Ki) was found to be 2 x 10(3) mM-1 min-1. Incubation with thetruncated compound, chloroacetol phosphate, resulted in no detectableinactivation when tested under comparable conditions. This supports thenotion that uridine 5'-diphosphate-chloroacetol is bound in the place ofUDP-glucose and is not simply acting as a nonspecific alkylating agent.
- Roychoudhury S, May TB, Gill JF, Singh SK, Feingold DS, Chakrabarty AM
- Purification and characterization of guanosine diphospho-D-mannosedehydrogenase. A key enzyme in the biosynthesis of alginate by Pseudomonasaeruginosa.
- J Biol Chem. 1989; 264: 9380-5
- Display abstract
Alginate-producing Pseudomonas aeruginosa are usually associated with thecystic fibrosis lung environment and contribute to the high mortalityrates observed among these patients. The present paper describes thepurification and enzymatic properties of guanosine diphospho-D-mannosedehydrogenase (EC 1.1.1.132), a key enzyme in alginate biosynthesis bymucoid P. aeruginosa. The enzyme was overproduced using a plasmid vectorcontaining algD (the gene encoding this enzyme) under control of the tacpromoter. It was purified from cell-free lysates by lowering the pH to5.0, heating the extract to 57.5 degrees C for 10 min, and discarding theprotein pellet. The enzyme was selectively precipitated from thesupernatant fraction with 45% acetone, resuspended in a 100 mMtriethanolamine acetate buffer, pH 7.6, and ultimately purified by Bio-SilTSK-400 gel filtration chromatography. The subunit molecular weight (Mr48,000) as well as the N-terminal amino acid sequence corresponded tothose predicted from the DNA sequence of algD. The native protein migratedas a hexamer of 290,000 molecular weight upon Bio-Gel A-1.5m gelfiltration chromatography. Kinetic analysis demonstrated an apparent Km of14.9 microM for the substrate GDP-D-mannose and 185 microM for thecofactor NAD+. GDP-D-mannuronic acid was identified as the enzyme reactionproduct. Several compounds (including GMP, ATP, GDP-D-glucose, andmaltose) were found to inhibit enzymatic activity. GMP, the most potent ofthese inhibitors, exhibited competitive inhibition with an apparent Ki of22.7 microM. Enzyme activity was also sensitive to the sulfhydryl groupmodifying agents iodoacetamide and p-hydroxymercuribenzoate. The additionof excess dithiothreitol restored enzyme activity, suggesting a possibleinvolvement of cysteine residues in enzymatic activity.
- Structure (3D structures containing this domain)
3D Structures of UDPG_MGDP_dh_C domains in PDB
| PDB code | Main view | Title | | 1dli |  | The first structure of udp-glucose dehydrogenase (udpgdh) reveals the catalytic residues necessary for the two-fold oxidation |
| 1dlj |  | The first structure of udp-glucose dehydrogenase (udpgdh) reveals the catalytic residues necessary for the two-fold oxidation |
| 1mfz |  | Partially refined 2.8 a crystal structure of gdp-mannose dehydrogenase from p. aeruginosa |
| 1muu |  | 2.0 a crystal structure of gdp-mannose dehydrogenase |
| 1mv8 |  | 1.55 a crystal structure of a ternary complex of gdp- mannose dehydrogenase from psuedomonas aeruginosa |
| 2o3j |  | Structure of caenorhabditis elegans udp-glucose dehydrogenase |
| 2q3e |  | Structure of human udp-glucose dehydrogenase complexed with nadh and udp-glucose |
| 2qg4 |  | Crystal structure of human udp-glucose dehydrogenase product complex with udp-glucuronate |
| 3g79 |  | Crystal structure of ndp-n-acetyl-d-galactosaminuronic acid dehydrogenase from methanosarcina mazei go1 |
| 3gg2 |  | Crystal structure of udp-glucose 6-dehydrogenase from porphyromonas gingivalis bound to product udp-glucuronate |
| 3itk |  | Crystal structure of human udp-glucose dehydrogenase thr131ala, apo form. |
| 3khu |  | Crystal structure of human udp-glucose dehydrogenase glu161gln, in complex with thiohemiacetal intermediate |
- Links (links to other resources describing this domain)
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to expand nodes. To display all proteins with a UDPG_MGDP_dh_C domain in a specific node, click on it.