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Escherichia coli K-12 substr. MG1655 Enzyme: dihydroneopterin aldolase



Gene: folB Accession Numbers: EG11673 (EcoCyc), b3058, ECK3048

Synonyms: ygiG

Regulation Summary Diagram: ?

Subunit composition of dihydroneopterin aldolase = [FolB]8
         dihydroneopterin aldolase = FolB

Summary:
Dihydroneopterin aldolase (FolB) is an enzyme in the folate biosynthesis pathway, an important antibacterial drug target.

The reaction mechanism has been investigated. The conserved Y53 residue is important for the aldolase reaction [Wang06a]. Site-directed mutagenesis of conserved active site residues suggested that E22 is important for substrate binding, but not catalysis, and that E21 and K98 are important for both substrate binding and catalysis [Wang06b]. Unlike other aldolase-catalyzed reactions, the dihydroneopterin aldolase reaction was initially found to be irreversible [Mathis70]. However, with an enzyme preparation of higher activity and a higher glycolaldehyde concentration, the reaction catalyzed by the Staphylococcus aureus enzyme is readily reversible [Wang07e].

FolB can also catalyze the reversible epimerization of the 3' position of dihydroneopterin, yielding dihydromonapterin [Haussmann98]. This reaction appears to use the same reaction intermediate as the aldolase reaction [Wang07e].

Review: [Bermingham02]

Locations: cytosol

Map Position: [3,202,243 <- 3,202,611] (69.02 centisomes)
Length: 369 bp / 122 aa

Molecular Weight of Polypeptide: 13.62 kD (from nucleotide sequence)

Molecular Weight of Multimer: 104 kD (experimental) [Haussmann98]

Unification Links: ASAP:ABE-0010036 , DIP:DIP-36044N , EchoBASE:EB1624 , EcoGene:EG11673 , EcoliWiki:b3058 , ModBase:P0AC16 , OU-Microarray:b3058 , PortEco:folB , PR:PRO_000022677 , Pride:P0AC16 , Protein Model Portal:P0AC16 , RefSeq:NP_417530 , RegulonDB:EG11673 , SMR:P0AC16 , String:511145.b3058 , Swiss-Model:P0AC16 , UniProt:P0AC16

Relationship Links: InterPro:IN-FAMILY:IPR006156 , InterPro:IN-FAMILY:IPR006157 , PDB:Structure:2O90 , Pfam:IN-FAMILY:PF02152 , Smart:IN-FAMILY:SM00905

In Paralogous Gene Group: 406 (2 members)

Gene-Reaction Schematic: ?

GO Terms:

Biological Process: GO:0006760 - folic acid-containing compound metabolic process Inferred by computational analysis [GOA01a]
GO:0046654 - tetrahydrofolate biosynthetic process Inferred by computational analysis [UniProtGOA12]
GO:0046656 - folic acid biosynthetic process Inferred by computational analysis [UniProtGOA11a]
Molecular Function: GO:0004150 - dihydroneopterin aldolase activity Inferred from experiment Inferred by computational analysis [GOA01, GOA01a, Haussmann98]
GO:0016829 - lyase activity Inferred by computational analysis [UniProtGOA11a]
Cellular Component: GO:0005829 - cytosol Inferred by computational analysis [DiazMejia09]

MultiFun Terms: metabolism biosynthesis of building blocks cofactors, small molecule carriers folic acid

Essentiality data for folB 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 No 37 Aerobic 7.2 0.35 No [Joyce06]
MOPS medium with 0.4% glucose Yes 37 Aerobic 7.2 0.22 Yes [Baba06, Comment 2]
Yes [Feist07, Comment 3]

Credits:
Created 04-Jan-2006 by Keseler I , SRI International
Last-Curated ? 12-Jul-2011 by Keseler I , SRI International


Enzymatic reaction of: dihydroneopterin aldolase

Synonyms: 2-amino-4-hydroxy-6-(D-erythro-1,2,3-trihydroxypropyl)-7,8-dihydropteridine glycoaldehyde-lyase, DHNA

EC Number: 4.1.2.25

7,8-dihydroneopterin <=> glycolaldehyde + 6-hydroxymethyl-7,8-dihydropterin

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.

Alternative Substrates for 7,8-dihydroneopterin: 7,8-dihydromonapterin [Haussmann98 ]

In Pathways: superpathway of chorismate metabolism , superpathway of tetrahydrofolate biosynthesis , 6-hydroxymethyl-dihydropterin diphosphate biosynthesis I

Summary:
The enzyme was first purified from E. coli B [Mathis70].

Kinetics of the enzyme were determined at 37°C [Haussmann98]. Binding constants of wild type and mutant enzymes were determined in [Wang06a, Wang06b, Wang07e].

Kinetic Parameters:

Substrate
Km (μM)
Vmax (µmol mg-1 min-1)
Citations
7,8-dihydroneopterin
64.0
2.12
[Haussmann98]

T(opt): 70 °C [Haussmann98]


Enzymatic reaction of: dihydroneopterin epimerase (dihydroneopterin aldolase)

7,8-dihydroneopterin <=> 7,8-dihydromonapterin

The reaction direction shown, that is, A + B ↔ C + D versus C + D ↔ A + B, is in accordance with the direction of enzyme catalysis.

This reaction is reversible. [Haussmann98]

Summary:
Dihydroneopterin aldolase also catalyzes the epimizeration of dihydroneopterin at position 3' to produce dihydromonapterin, with similar rates in the forward and reverse directions [Haussmann98].

Kinetic Parameters:

Substrate
Km (μM)
Citations
7,8-dihydroneopterin
45.0
[Haussmann98]


Sequence Features

Feature Class Location Citations Comment
Sequence-Conflict 81 -> 82
[Cain93, UniProt10]
Alternate sequence: EL → DV; UniProt: (in Ref. 1; L12966);
Sequence-Conflict 100 -> 122
[Cain93, UniProt10]
Alternate sequence: GAVARAANVGVIIERGNNLKENN → ASGAGGECWRNH; UniProt: (in Ref. 1; L12966);


Gene Local Context (not to scale): ?

Transcription Unit:

Notes:

History:
Peter D. Karp on Wed Jan 18, 2006:
Gene right-end position adjusted based on analysis performed in the 2005 E. coli annotation update [Riley06 ].
10/20/97 Gene b3058 from Blattner lab Genbank (v. M52) entry merged into EcoCyc gene EG11673; confirmed by SwissProt match.


References

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

Bermingham02: Bermingham A, Derrick JP (2002). "The folic acid biosynthesis pathway in bacteria: evaluation of potential for antibacterial drug discovery." Bioessays 24(7);637-48. PMID: 12111724

Cain93: Cain BD, Norton PJ, Eubanks W, Nick HS, Allen CM (1993). "Amplification of the bacA gene confers bacitracin resistance to Escherichia coli." J Bacteriol 175(12);3784-9. PMID: 8389741

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

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."

Haussmann98: Haussmann C, Rohdich F, Schmidt E, Bacher A, Richter G (1998). "Biosynthesis of pteridines in Escherichia coli. Structural and mechanistic similarity of dihydroneopterin-triphosphate epimerase and dihydroneopterin aldolase." J Biol Chem 273(28);17418-24. PMID: 9651328

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

Mathis70: Mathis JB, Brown GM (1970). "The biosynthesis of folic acid. XI. Purification and properties of dihydroneopterin aldolase." J Biol Chem 1970;245(11);3015-25. PMID: 4912541

Riley06: Riley M, Abe T, Arnaud MB, Berlyn MK, Blattner FR, Chaudhuri RR, Glasner JD, Horiuchi T, Keseler IM, Kosuge T, Mori H, Perna NT, Plunkett G, Rudd KE, Serres MH, Thomas GH, Thomson NR, Wishart D, Wanner BL (2006). "Escherichia coli K-12: a cooperatively developed annotation snapshot--2005." Nucleic Acids Res 34(1);1-9. PMID: 16397293

UniProt10: UniProt Consortium (2010). "UniProt version 2010-11 released on 2010-11-02 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."

Wang06a: Wang Y, Scherperel G, Roberts KD, Jones AD, Reid GE, Yan H (2006). "A point mutation converts dihydroneopterin aldolase to a cofactor-independent oxygenase." J Am Chem Soc 128(40);13216-23. PMID: 17017801

Wang06b: Wang Y, Li Y, Yan H (2006). "Mechanism of dihydroneopterin aldolase: functional roles of the conserved active site glutamate and lysine residues." Biochemistry 45(51);15232-9. PMID: 17176045

Wang07e: Wang Y, Li Y, Wu Y, Yan H (2007). "Mechanism of dihydroneopterin aldolase. NMR, equilibrium and transient kinetic studies of the Staphylococcus aureus and Escherichia coli enzymes." FEBS J 274(9):2240-52. PMID: 17388809


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 Sun Dec 21, 2014, BIOCYC14B.