SMART: UDPG_MGDP_dh_C domain annotation

UDPG_MGDP_dh_C UDP binding domain

SMART accession number:	SM00984
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).
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) ].
GO process:	oxidation-reduction process (GO:0055114)
GO function:	oxidoreductase activity, acting on the CH-OH group of donors, NAD or NADP as acceptor (GO:0016616), NAD binding (GO:0051287)
Family alignment:	View or

There are 44356 UDPG_MGDP_dh_C domains in 44348 proteins in SMART's nrdb database.

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Evolution (species in which this domain is found)
Taxonomic distribution of proteins containing UDPG_MGDP_dh_C domain.
This tree includes only several representative species. The complete taxonomic breakdown of all proteins with UDPG_MGDP_dh_C domain is also avaliable.

Click on the protein counts, or double click on taxonomic names to display all proteins containing UDPG_MGDP_dh_C domain in the selected taxonomic class.
Cellular role (predicted cellular role)
Cellular role: metabolism
Literature (relevant references for this domain)
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
2y0c		BceC mutation Y10S
2y0d		BceC mutation Y10K
2y0e		BceC and the final step of UGDs reaction
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
3ojl		Native structure of the UDP-N-acetyl-mannosamine dehydrogenase Cap5O from Staphylococcus aureus
3ojo		Derivative structure of the UDP-N-acetyl-mannosamine dehydrogenase Cap5O from S. aureus
3phl		The apo-form UDP-glucose 6-dehydrogenase
3pid		The apo-form UDP-glucose 6-dehydrogenase with a C-terminal six-histidine tag
3pjg		Crystal structure of UDP-glucose dehydrogenase from Klebsiella pneumoniae complexed with product UDP-glucuronic acid
3pln		Crystal structure of Klebsiella pneumoniae UDP-glucose 6-dehydrogenase complexed with UDP-glucose
3plr		Crystal structure of Klebsiella pneumoniae UDP-glucose 6-dehydrogenase complexed with NADH and UDP-glucose
3prj		Role of Packing Defects in the Evolution of Allostery and Induced Fit in Human UDP-Glucose Dehydrogenase.
3ptz		Role of Packing Defects in the Evolution of Allostery and Induced Fit in Human UDP-Glucose Dehydrogenase.
3tdk		Crystal Structure of Human UDP-Glucose Dehydrogenase
3tf5		Structure of UDP-glucose dehydrogenase V132 deletion
3vtf		Structure of a UDP-glucose dehydrogenase from the hyperthermophilic archaeon Pyrobaculum islandicum
4a7p		Se-Met derivatized UgdG, UDP-glucose dehydrogenase from Sphingomonas elodea
4edf		Dimeric hUGDH, K94E
4qej		4QEJ
4r16		4R16
4rjt		4RJT
4xr9		4XR9
4xrr		4XRR
5tjh		5TJH

Links (links to other resources describing this domain)
INTERPRO IPR014027
PFAM UDPG_MGDP_dh_C

UDPG_MGDP_dh_C

Taxonomic distribution of proteins containing UDPG_MGDP_dh_C domain.

3D Structures of UDPG_MGDP_dh_C domains in PDB