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Escherichia coli K-12 substr. MG1655 Enzyme: dihydromonapterin reductase / dihydrofolate reductase



Gene: folM Accession Numbers: G6862 (EcoCyc), b1606, ECK1601

Synonyms: ydgB

Regulation Summary Diagram: ?

Summary:
FolM is a dihydromonapterin reductase. The activity of the enzyme with the dihydromonapterin substrate is 16-fold higher than with dihydrofolate. Neither dihydroneopterin nor monapterin are substrates [Pribat10].

Overexpression of folM from a plasmid can complement the severe growth defect of a folA deletion mutant. A folM deletion mutant has no detectable growth defect [Giladi03], but disruption of either folM or folX leads to decreased sensitivity to the antibiotics trimethoprim and sulfamonomethoxine [Girgis09].

Locations: cytosol

Map Position: [1,679,000 -> 1,679,722] (36.19 centisomes)
Length: 723 bp / 240 aa

Molecular Weight of Polypeptide: 26.348 kD (from nucleotide sequence)

Unification Links: ASAP:ABE-0005364 , DIP:DIP-47981N , EchoBASE:EB2981 , EcoGene:EG13189 , EcoliWiki:b1606 , Entrez-gene:949096 , ModBase:P0AFS3 , OU-Microarray:b1606 , PortEco:folM , PR:PRO_000022681 , Protein Model Portal:P0AFS3 , RefSeq:NP_416123 , RegulonDB:G6862 , SMR:P0AFS3 , String:511145.b1606 , UniProt:P0AFS3

Relationship Links: InterPro:IN-FAMILY:IPR002198 , InterPro:IN-FAMILY:IPR002347 , InterPro:IN-FAMILY:IPR016040 , InterPro:IN-FAMILY:IPR020904 , Pfam:IN-FAMILY:PF00106 , Prints:IN-FAMILY:PR00081 , Prosite:IN-FAMILY:PS00061

Gene-Reaction Schematic: ?

GO Terms:

Biological Process: GO:0009257 - 10-formyltetrahydrofolate biosynthetic process Inferred from experiment [Giladi03]
GO:0046656 - folic acid biosynthetic process Inferred from experiment [Giladi03]
GO:0006730 - one-carbon metabolic process Inferred by computational analysis [UniProtGOA11a]
GO:0008152 - metabolic process Inferred by computational analysis [GOA01a]
GO:0055114 - oxidation-reduction process Inferred by computational analysis [UniProtGOA11a]
Molecular Function: GO:0071172 - dihydromonapterin reductase activity Inferred from experiment [Pribat10]
GO:0004146 - dihydrofolate reductase activity Inferred by computational analysis [GOA01]
GO:0016491 - oxidoreductase activity Inferred by computational analysis [UniProtGOA11a, GOA01a]
Cellular Component: GO:0005829 - cytosol Inferred by computational analysis [DiazMejia09]

MultiFun Terms: metabolism biosynthesis of building blocks cofactors, small molecule carriers folic acid
metabolism central intermediary metabolism formyl-THF biosynthesis

Essentiality data for folM 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:
Last-Curated ? 20-Nov-2009 by Keseler I , SRI International


Enzymatic reaction of: dihydromonapterin reductase

EC Number: 1.5.1.-

7,8-dihydromonapterin + NADPH + H+ <=> tetrahydromonapterin + NADP+

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

The reaction is physiologically favored in the direction shown.

In Pathways: tetrahydromonapterin biosynthesis

Summary:
The enzyme is specific for NADPH as a cofactor [Pribat10].

Kinetic Parameters:

Substrate
Km (μM)
Citations
7,8-dihydromonapterin
147.0
[Pribat10]


Enzymatic reaction of: dihydrofolate reductase

Synonyms: 5,6,7,8-tetrahydrofolate:NADP+ oxidoreductase, tetrahydrofolate dehydrogenase

EC Number: 1.5.1.3

a tetrahydrofolate + NADP+ <=> a 7,8-dihydrofolate + NADPH + 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 opposite direction.

In Pathways: superpathway of chorismate metabolism , superpathway of tetrahydrofolate biosynthesis , tetrahydrofolate biosynthesis , N10-formyl-tetrahydrofolate biosynthesis

Summary:
The enzyme can not reduce folate or biopterin [Giladi03].

Inhibitors (Competitive): methotrexate [Giladi03]

Kinetic Parameters:

Substrate
Km (μM)
Citations
a 7,8-dihydrofolate
9.5
[Giladi03]
NADPH
1.9
[Giladi03]

pH(opt): 4.7 [Giladi03]


Sequence Features

Feature Class Location Citations Comment
Active-Site 152
[UniProt10]
UniProt: Proton acceptor; Non-Experimental Qualifier: by similarity;
Sequence-Conflict 210
[Kuempel95, UniProt10a]
Alternate sequence: E → Q; UniProt: (in Ref. 4);


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

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

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

Giladi03: Giladi M, Altman-Price N, Levin I, Levy L, Mevarech M (2003). "FolM, a new chromosomally encoded dihydrofolate reductase in Escherichia coli." J Bacteriol 185(23);7015-8. PMID: 14617668

Girgis09: Girgis HS, Hottes AK, Tavazoie S (2009). "Genetic architecture of intrinsic antibiotic susceptibility." PLoS One 4(5);e5629. PMID: 19462005

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."

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

Kuempel95: Kuempel P.L. (1995). Data submission to EMBL/GenBank/DDBJ databases on 1995-11.

Pribat10: Pribat A, Blaby IK, Lara-Nunez A, Gregory JF, de Crecy-Lagard V, Hanson AD (2010). "FolX and FolM Are Essential for Tetrahydromonapterin Synthesis in Escherichia coli and Pseudomonas aeruginosa." J Bacteriol 192(2):475-82. PMID: 19897652

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

UniProt10a: 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."


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 Thu Dec 18, 2014, biocyc14.