Metabolic Modeling Tutorial
discounted EARLY registration ends Dec 31, 2014
BioCyc websites down
12/28 - 12/31
for maintenance.
Metabolic Modeling Tutorial
discounted EARLY registration ends Dec 31, 2014
BioCyc websites down
12/28 - 12/31
for maintenance.
Metabolic Modeling Tutorial
discounted EARLY registration ends Dec 31, 2014
BioCyc websites down
12/28 - 12/31
for maintenance.
Metabolic Modeling Tutorial
discounted EARLY registration ends Dec 31, 2014
BioCyc websites down
12/28 - 12/31
for maintenance.
Metabolic Modeling Tutorial
discounted EARLY registration ends Dec 31, 2014
BioCyc websites down
12/28 - 12/31
for maintenance.
twitter

Escherichia coli K-12 substr. MG1655 Enzyme: UDP-glucose 6-dehydrogenase



Gene: ugd Accession Numbers: G7091 (EcoCyc), b2028, ECK2023

Synonyms: yefA, udg, UDG8, pmrE

Regulation Summary Diagram: ?

Subunit composition of UDP-glucose 6-dehydrogenase = [Ugd]2

Summary:
UDP-glucose dehydrogenase (Ugd) catalyzes the synthesis of UDP-glucaronic acid. Ugd activity is activated by tyrosine phosphorylation catalyzed by the tyrosine kinase Wzc [Grangeasse03]. Ugd is also phosphorylated by Etk. Both Wzc and and Etk are BY-kinases which catalyze protein tyrosine phosphorylation. Phosphorylation of Ugd by Wzc was found to regulate the amount of colanic acid, while Etk was involved in the resistance to polymyxin. [Lacour08]

Overproduction of UDP-glucose dehydrogenase reduces production of K5 polysaccharide during exogenous expression of the K5 biosynthesis gene cluster [Roman03].

ugd is found in a cluster of genes found to be necessarcy for the production of colonic acid [Stevenson96]. Mutagenesis of ugd showed the essential role of this gene in K30 biosynthesis and that there are no additional functional ugd copies. [Drummelsmith97] Mutations in the UDP-glucaronic acid allosteric binding site decreased the binding affinity of the nucleotide triphosphate [Mainprize13].

In Salmonella, two 2-component system systems are required for ugd expression in response to low Mg2+ [Groisman97, Gunn98, Soncini96].

Citations: [Amor97, Mouslim03, Klein13]

Locations: cytosol

Map Position: [2,096,471 <- 2,097,637] (45.19 centisomes)
Length: 1167 bp / 388 aa

Molecular Weight of Polypeptide: 43.657 kD (from nucleotide sequence)

Molecular Weight of Multimer: 86.0 kD (experimental) [Schiller73]

Unification Links: ASAP:ABE-0006734 , EchoBASE:EB3183 , EcoGene:EG13407 , EcoliWiki:b2028 , ModBase:P76373 , OU-Microarray:b2028 , PortEco:ugd , Pride:P76373 , Protein Model Portal:P76373 , RefSeq:NP_416532 , RegulonDB:G7091 , SMR:P76373 , String:511145.b2028 , Swiss-Model:P76373 , UniProt:P76373

Relationship Links: InterPro:IN-FAMILY:IPR001732 , InterPro:IN-FAMILY:IPR008927 , InterPro:IN-FAMILY:IPR013328 , InterPro:IN-FAMILY:IPR014026 , InterPro:IN-FAMILY:IPR014027 , InterPro:IN-FAMILY:IPR016040 , InterPro:IN-FAMILY:IPR017476 , InterPro:IN-FAMILY:IPR028357 , Panther:IN-FAMILY:PTHR11374 , Pfam:IN-FAMILY:PF00984 , Pfam:IN-FAMILY:PF03720 , Pfam:IN-FAMILY:PF03721 , Smart:IN-FAMILY:SM00984

In Paralogous Gene Group: 368 (2 members)

Gene-Reaction Schematic: ?

GO Terms:

Biological Process: GO:0009242 - colanic acid biosynthetic process Inferred from experiment [Lacour08]
GO:0000271 - polysaccharide biosynthetic process Inferred by computational analysis [GOA01a]
GO:0006065 - UDP-glucuronate biosynthetic process Inferred by computational analysis [UniProtGOA12]
GO:0009103 - lipopolysaccharide biosynthetic process Inferred by computational analysis [UniProtGOA12]
GO:0055114 - oxidation-reduction process Inferred by computational analysis [UniProtGOA11a, GOA01a]
Molecular Function: GO:0003979 - UDP-glucose 6-dehydrogenase activity Inferred from experiment Inferred by computational analysis [GOA01, GOA01a, Grangeasse03, Roman03]
GO:0005515 - protein binding Inferred from experiment [Rajagopala14]
GO:0016491 - oxidoreductase activity Inferred by computational analysis [UniProtGOA11a, GOA01a]
GO:0016616 - oxidoreductase activity, acting on the CH-OH group of donors, NAD or NADP as acceptor Inferred by computational analysis [GOA01a]
GO:0050662 - coenzyme binding Inferred by computational analysis [GOA01a]
GO:0051287 - NAD binding Inferred by computational analysis [GOA01a]
Cellular Component: GO:0005829 - cytosol Inferred by computational analysis [DiazMejia09]

MultiFun Terms: cell processes adaptations dessication
cell structure capsule (M and K antigens)
cell structure surface antigens (ECA, O antigen of LPS)
metabolism biosynthesis of macromolecules (cellular constituents) colanic acid (M antigen)

Essentiality data for ugd knockouts: ?

Growth Medium Growth? T (°C) O2 pH Osm/L Growth Observations
LB enriched Yes 37 Aerobic 6.95   Yes [Gerdes03, Comment 1]
LB Lennox Yes 37 Aerobic 7   Yes [Baba06, Comment 2]
M9 medium with 1% glycerol Yes 37 Aerobic 7.2 0.35 Yes [Joyce06, Comment 3]
MOPS medium with 0.4% glucose Yes 37 Aerobic 7.2 0.22 Yes [Baba06, Comment 2]
Yes [Feist07, Comment 4]

Credits:
Created 12-Nov-2013 by Kubo A , SRI International


Enzymatic reaction of: UDP-glucose 6-dehydrogenase

Synonyms: UDPglucose:NAD+ 6-oxidoreductase, UDP-Glc dehydrogenase

EC Number: 1.1.1.22

UDP-α-D-glucose + 2 NAD+ + H2O <=> UDP-α-D-glucuronate + 2 NADH + 3 H+

The reaction direction shown, that is, A + B ↔ C + D versus C + D ↔ A + B, is in accordance with the Enzyme Commission system.

The reaction is favored in the direction shown.

In Pathways: colanic acid building blocks biosynthesis , UDP-α-D-glucuronate biosynthesis (from UDP-glucose)

Summary:
Four different nucleotide sugars are required for the production of the E. coli colanic acid repeat unit (the E-unit). UDP-glucose 6-dehydrogenase catalyzes the synthesis of one of them, UDP-glucuronate. [Stevenson96]

Activators (Unknown Mechanism): NADH [Schiller73]

Kinetic Parameters:

Substrate
Km (μM)
Citations
UDP-α-D-glucose
1000.0
[Schiller73]
NAD+
50.0
[Schiller73, BRENDA14]
NAD+
620.0
[Grangeasse03]

pH(opt): 9.0 [BRENDA14, Schiller73]


Sequence Features

Feature Class Location Citations Comment
Nucleotide-Phosphate-Binding-Region 2 -> 19
[UniProt10]
UniProt: NAD; Non-Experimental Qualifier: potential;
Active-Site 253
[UniProt10]
UniProt: Non-Experimental Qualifier: by similarity;


Gene Local Context (not to scale): ?

Transcription Unit:

Notes:

History:
Markus Krummenacker on Tue Oct 14, 1997:
Gene object created from Blattner lab Genbank (v. M52) entry.


References

Amor97: Amor PA, Whitfield C (1997). "Molecular and functional analysis of genes required for expression of group IB K antigens in Escherichia coli: characterization of the his-region containing gene clusters for multiple cell-surface polysaccharides." Mol Microbiol 26(1);145-61. PMID: 9383197

Baba06: Baba T, Ara T, Hasegawa M, Takai Y, Okumura Y, Baba M, Datsenko KA, Tomita M, Wanner BL, Mori H (2006). "Construction of Escherichia coli K-12 in-frame, single-gene knockout mutants: the Keio collection." Mol Syst Biol 2;2006.0008. PMID: 16738554

BRENDA14: BRENDA team (2014). "Imported from BRENDA version existing on Aug 2014." http://www.brenda-enzymes.org.

DiazMejia09: Diaz-Mejia JJ, Babu M, Emili A (2009). "Computational and experimental approaches to chart the Escherichia coli cell-envelope-associated proteome and interactome." FEMS Microbiol Rev 33(1);66-97. PMID: 19054114

Drummelsmith97: Drummelsmith J, Amor PA, Whitfield C (1997). "Polymorphism, duplication, and IS1-mediated rearrangement in the chromosomal his-rfb-gnd region of Escherichia coli strains with group IA and capsular K antigens." J Bacteriol 179(10);3232-8. PMID: 9150218

Feist07: Feist AM, Henry CS, Reed JL, Krummenacker M, Joyce AR, Karp PD, Broadbelt LJ, Hatzimanikatis V, Palsson BO (2007). "A genome-scale metabolic reconstruction for Escherichia coli K-12 MG1655 that accounts for 1260 ORFs and thermodynamic information." Mol Syst Biol 3;121. PMID: 17593909

Gerdes03: Gerdes SY, Scholle MD, Campbell JW, Balazsi G, Ravasz E, Daugherty MD, Somera AL, Kyrpides NC, Anderson I, Gelfand MS, Bhattacharya A, Kapatral V, D'Souza M, Baev MV, Grechkin Y, Mseeh F, Fonstein MY, Overbeek R, Barabasi AL, Oltvai ZN, Osterman AL (2003). "Experimental determination and system level analysis of essential genes in Escherichia coli MG1655." J Bacteriol 185(19);5673-84. PMID: 13129938

GOA01: GOA, MGI (2001). "Gene Ontology annotation based on Enzyme Commission mapping." Genomics 74;121-128.

GOA01a: GOA, DDB, FB, MGI, ZFIN (2001). "Gene Ontology annotation through association of InterPro records with GO terms."

Grangeasse03: Grangeasse C, Obadia B, Mijakovic I, Deutscher J, Cozzone AJ, Doublet P (2003). "Autophosphorylation of the Escherichia coli protein kinase Wzc regulates tyrosine phosphorylation of Ugd, a UDP-glucose dehydrogenase." J Biol Chem 278(41);39323-9. PMID: 12851388

Groisman97: Groisman EA, Kayser J, Soncini FC (1997). "Regulation of polymyxin resistance and adaptation to low-Mg2+ environments." J Bacteriol 179(22);7040-5. PMID: 9371451

Gunn98: Gunn JS, Lim KB, Krueger J, Kim K, Guo L, Hackett M, Miller SI (1998). "PmrA-PmrB-regulated genes necessary for 4-aminoarabinose lipid A modification and polymyxin resistance." Mol Microbiol 27(6);1171-82. PMID: 9570402

Joyce06: Joyce AR, Reed JL, White A, Edwards R, Osterman A, Baba T, Mori H, Lesely SA, Palsson BO, Agarwalla S (2006). "Experimental and computational assessment of conditionally essential genes in Escherichia coli." J Bacteriol 188(23);8259-71. PMID: 17012394

Klein13: Klein G, Muller-Loennies S, Lindner B, Kobylak N, Brade H, Raina S (2013). "Molecular and structural basis of inner core lipopolysaccharide alterations in Escherichia coli: incorporation of glucuronic acid and phosphoethanolamine in the heptose region." J Biol Chem 288(12);8111-27. PMID: 23372159

Lacour08: Lacour S, Bechet E, Cozzone AJ, Mijakovic I, Grangeasse C (2008). "Tyrosine phosphorylation of the UDP-glucose dehydrogenase of Escherichia coli is at the crossroads of colanic acid synthesis and polymyxin resistance." PLoS One 3(8);e3053. PMID: 18725960

Mainprize13: Mainprize IL, Bean JD, Bouwman C, Kimber MS, Whitfield C (2013). "The UDP-glucose dehydrogenase of Escherichia coli K-12 displays substrate inhibition by NAD that is relieved by nucleotide triphosphates." J Biol Chem 288(32);23064-74. PMID: 23792965

Mouslim03: Mouslim C, Latifi T, Groisman EA (2003). "Signal-dependent requirement for the co-activator protein RcsA in transcription of the RcsB-regulated ugd gene." J Biol Chem 278(50);50588-95. PMID: 14514676

Rajagopala14: Rajagopala SV, Sikorski P, Kumar A, Mosca R, Vlasblom J, Arnold R, Franca-Koh J, Pakala SB, Phanse S, Ceol A, Hauser R, Siszler G, Wuchty S, Emili A, Babu M, Aloy P, Pieper R, Uetz P (2014). "The binary protein-protein interaction landscape of Escherichia coli." Nat Biotechnol 32(3);285-90. PMID: 24561554

Roman03: Roman E, Roberts I, Lidholt K, Kusche-Gullberg M (2003). "Overexpression of UDP-glucose dehydrogenase in Escherichia coli results in decreased biosynthesis of K5 polysaccharide." Biochem J 374(Pt 3);767-72. PMID: 12775214

Schiller73: Schiller JG, Bowser AM, Feingold DS (1973). "Partial purification and properties of UDPG dehydrogenase from Escherichia coli." Biochim Biophys Acta 293(1);1-10. PMID: 4568129

Soncini96: Soncini FC, Garcia Vescovi E, Solomon F, Groisman EA (1996). "Molecular basis of the magnesium deprivation response in Salmonella typhimurium: identification of PhoP-regulated genes." J Bacteriol 178(17);5092-9. PMID: 8752324

Stevenson96: Stevenson G, Andrianopoulos K, Hobbs M, Reeves PR (1996). "Organization of the Escherichia coli K-12 gene cluster responsible for production of the extracellular polysaccharide colanic acid." J Bacteriol 1996;178(16);4885-93. PMID: 8759852

UniProt10: UniProt Consortium (2010). "UniProt version 2010-07 released on 2010-06-15 00:00:00." Database.

UniProtGOA11a: UniProt-GOA (2011). "Gene Ontology annotation based on manual assignment of UniProtKB keywords in UniProtKB/Swiss-Prot entries."

UniProtGOA12: UniProt-GOA (2012). "Gene Ontology annotation based on UniPathway vocabulary mapping."


Report Errors or Provide Feedback
Please cite the following article in publications resulting from the use of EcoCyc: Nucleic Acids Research 41:D605-12 2013
Page generated by SRI International Pathway Tools version 18.5 on Sat Dec 20, 2014, biocyc12.