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MetaCyc Enzyme: bifunctional 5,10-methylene-tetrahydrofolate dehydrogenase/ 5,10-methylene-tetrahydrofolate cyclohydrolase

Gene: folD Accession Numbers: EG10328 (MetaCyc), b0529, ECK0522

Synonyms: ads

Species: Escherichia coli K-12 substr. MG1655

Subunit composition of bifunctional 5,10-methylene-tetrahydrofolate dehydrogenase/ 5,10-methylene-tetrahydrofolate cyclohydrolase = [FolD]2

Summary:
E. coli folD gene product is a bifunctional enzyme with both methylenetetrahydrofolate dehydrogenase and methenyltetrahydrofolate cyclohydrolase activities. This enzyme is active as a homodimer. The dehydrogenase and cyclohydrolase activities reversibly catalyze the oxidation of N5,N10-methylenetetrahydrofolate to N5,N10-methenyltetrahydrofolate and the hydrolysis of N5,N10-methenyltetrahydrofolate to N10-formyltetrahydrofolate. These two enzymes, the dehydrogenase and the cyclohydrolase, permit N5,N10-methylenetetrahydrofolate to supply one-carbon units for the synthesis of carbons 2 and 8 of purines and the formyl group of N-formylmethionyl-tRNA(f). N5,N10-methylene-tetrahydrofolate is also the substrate of two other essential reactions. It is used directly in the synthesis of thymidylate and is reduced to N5-methyltetrahydrofolate for use in methionine synthesis [Shen99, Cheung97, DAri91, Dev78].

Locations: cytosol

Map Position: [556,098 <- 556,964]

Molecular Weight of Polypeptide: 31.044 kD (from nucleotide sequence)

pI: 6.06

Unification Links: ASAP:ABE-0001818 , CGSC:31127 , DIP:DIP-9675N , EchoBASE:EB0324 , EcoGene:EG10328 , EcoliWiki:b0529 , Entrez-gene:945221 , ModBase:P24186 , OU-Microarray:b0529 , PortEco:folD , PR:PRO_000022679 , Pride:P24186 , Protein Model Portal:P24186 , RefSeq:NP_415062.1 , RegulonDB:EG10328 , SMR:P24186 , String:511145.b0529 , UniProt:P24186

Relationship Links: InterPro:IN-FAMILY:IPR000672 , InterPro:IN-FAMILY:IPR016040 , InterPro:IN-FAMILY:IPR020630 , InterPro:IN-FAMILY:IPR020631 , InterPro:IN-FAMILY:IPR020867 , PDB:Structure:1B0A , Pfam:IN-FAMILY:PF00763 , Pfam:IN-FAMILY:PF02882 , Prints:IN-FAMILY:PR00085 , Prosite:IN-FAMILY:PS00766 , Prosite:IN-FAMILY:PS00767

Gene-Reaction Schematic: ?

GO Terms:

Biological Process: GO:0000105 - histidine biosynthetic process Inferred by computational analysis [UniProtGOA11a]
GO:0006164 - purine nucleotide biosynthetic process Inferred by computational analysis [UniProtGOA11a]
GO:0006730 - one-carbon metabolic process Inferred by computational analysis [UniProtGOA11a, Gaudet10]
GO:0008152 - metabolic process Inferred by computational analysis [UniProtGOA11a]
GO:0008652 - cellular amino acid biosynthetic process Inferred by computational analysis [UniProtGOA11a]
GO:0009086 - methionine biosynthetic process Inferred by computational analysis [UniProtGOA11a]
GO:0009396 - folic acid-containing compound biosynthetic process Inferred by computational analysis [GOA01a]
GO:0035999 - tetrahydrofolate interconversion Inferred by computational analysis [UniProtGOA12]
GO:0055114 - oxidation-reduction process Inferred by computational analysis [UniProtGOA11a, GOA01a]
Molecular Function: GO:0004477 - methenyltetrahydrofolate cyclohydrolase activity Inferred from experiment Inferred by computational analysis [GOA06, GOA01, Gaudet10, DAri91]
GO:0003824 - catalytic activity Inferred by computational analysis [UniProtGOA11a, GOA01a]
GO:0004488 - methylenetetrahydrofolate dehydrogenase (NADP+) activity Inferred by computational analysis [GOA06, GOA01, GOA01a, Gaudet10]
GO:0016491 - oxidoreductase activity Inferred by computational analysis [UniProtGOA11a]
GO:0016787 - hydrolase activity Inferred by computational analysis [UniProtGOA11a]
Cellular Component: GO:0005829 - cytosol Inferred from experiment Inferred by computational analysis [DiazMejia09, Ishihama08, Gaudet10]

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

Credits:
Reviewed in EcoCyc 04-Mar-2010 by Sarker M
Imported from EcoCyc 16-Sep-2014 by Paley S , SRI International


Enzymatic reaction of: methenyltetrahydrofolate cyclohydrolase (bifunctional 5,10-methylene-tetrahydrofolate dehydrogenase/ 5,10-methylene-tetrahydrofolate cyclohydrolase)

Synonyms: 5,10-methenyltetrahydrofolate 5-hydrolase (decyclizing)

EC Number: 3.5.4.9

a 5,10-methenyltetrahydrofolate + H2O <=> an N10-formyl-tetrahydrofolate + H+

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. [Shen99]

In Pathways: superpathway of tetrahydrofolate biosynthesis and salvage , tetrahydrofolate salvage from 5,10-methenyltetrahydrofolate , folate transformations I , N10-formyl-tetrahydrofolate biosynthesis

Credits:
Imported from EcoCyc 16-Sep-2014 by Paley S , SRI International

Inhibitors (Competitive): 10-formyl-tetrahydrofolate mono-L-glutamate [Dev78]


Enzymatic reaction of: methylenetetrahydrofolate dehydrogenase (bifunctional 5,10-methylene-tetrahydrofolate dehydrogenase/ 5,10-methylene-tetrahydrofolate cyclohydrolase)

Synonyms: 5,10-methylenetetrahydrofolate:NADP+ oxidoreductase

EC Number: 1.5.1.5

a 5,10-methylene-tetrahydrofolate + NADP+ <=> a 5,10-methenyltetrahydrofolate + NADPH

The reaction direction shown, that is, A + B ↔ C + D versus C + D ↔ A + B, is in accordance with the direction in which it was curated.

This reaction is reversible. [Shen99]

Alternative Substrates [Comment 1]:

In Pathways: folate transformations I , N10-formyl-tetrahydrofolate biosynthesis

Credits:
Imported from EcoCyc 16-Sep-2014 by Paley S , SRI International

Summary:
Binding of a single NADP cofactor per subunit occurs presumably at the dehydrogenase active site. Binding of two tetrahydrofolate cofactors occurs per subunit. The dehydrogenase activity is inhibited by several mono- and divalent salts. The pH optimum of the enzyme is approximately 8.5 [Cheung97].

Inhibitors (Competitive): ATP [Comment 2]

Inhibitors (Unknown Mechanism): tris [DAri91] , 2-mercaptoethanol [DAri91] , IMP [Dev78] , GTP [Dev78] , 10-formyl-tetrahydrofolate mono-L-glutamate [Comment 3]


Sequence Features

Feature Class Location Attached Group Citations Comment
Cleavage-of-Initial-Methionine 1  
[DAri91, UniProt11a]
UniProt: Removed.
Chain 2 -> 288  
[UniProt09]
UniProt: Bifunctional protein folD;
Sequence-Conflict 47  
[Chung97, UniProt10]
Alternate sequence: L; UniProt: (in Ref. 3; AAB40282);
Nucleotide-Phosphate-Binding-Region 166 -> 168 NADP+
[UniProt14]
UniProt: NADP; Non-Experimental Qualifier: by similarity.
Sequence-Conflict 200  
[DAri91, UniProt10]
Alternate sequence: L; UniProt: (in Ref. 1; AAA23803);
Amino-Acid-Sites-That-Bind 232  
[UniProt14]
UniProt: NADP; via amide nitrogen; Non-Experimental Qualifier: by similarity.

History:
10/20/97 Gene b0529 from Blattner lab Genbank (v. M52) entry merged into EcoCyc gene EG10328; confirmed by SwissProt match.


References

Cheung97: Cheung E, D'Ari L, Rabinowitz JC, Dyer DH, Huang JY, Stoddard BL (1997). "Purification, crystallization, and preliminary x-ray studies of a bifunctional 5,10-methenyl/methylene-tetrahydrofolate cyclohydrolase/dehydrogenase from Escherichia coli." Proteins 27(2);322-4. PMID: 9061797

Chung97: Chung E., Allen E., Araujo R., Aparicio A.M., Davis K., Duncan M., Federspiel N., Hyman R., Kalman S., Komp C., Kurdi O., Lew H., Lin D., Namath A., Oefner P., Roberts D., Schramm S., Davis R.W. (1997). "Sequence of minutes 4-25 of Escherichia coli." Data submission to EMBL/GenBank/DDBJ databases on 1997-01.

DAri91: D'Ari L, Rabinowitz JC (1991). "Purification, characterization, cloning, and amino acid sequence of the bifunctional enzyme 5,10-methylenetetrahydrofolate dehydrogenase/5,10-methenyltetrahydrofolate cyclohydrolase from Escherichia coli." J Biol Chem 1991;266(35);23953-8. PMID: 1748668

Dev78: Dev IK, Harvey RJ (1978). "A complex of N5,N10-methylenetetrahydrofolate dehydrogenase and N5,N10-methenyltetrahydrofolate cyclohydrolase in Escherichia coli. Purification, subunit structure, and allosteric inhibition by N10-formyltetrahydrofolate." J Biol Chem 1978;253(12);4245-53. PMID: 350870

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

Gaudet10: Gaudet P, Livstone M, Thomas P (2010). "Annotation inferences using phylogenetic trees." PMID: 19578431

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."

GOA06: GOA, SIB (2006). "Electronic Gene Ontology annotations created by transferring manual GO annotations between orthologous microbial proteins."

Ishihama08: Ishihama Y, Schmidt T, Rappsilber J, Mann M, Hartl FU, Kerner MJ, Frishman D (2008). "Protein abundance profiling of the Escherichia coli cytosol." BMC Genomics 9;102. PMID: 18304323

Shen99: Shen BW, Dyer DH, Huang JY, D'Ari L, Rabinowitz J, Stoddard BL (1999). "The crystal structure of a bacterial, bifunctional 5,10 methylene-tetrahydrofolate dehydrogenase/cyclohydrolase." Protein Sci 8(6);1342-9. PMID: 10386884

UniProt09: UniProt Consortium (2009). "UniProt version 15.8 released on 2009-10-01 00:00:00." Database.

UniProt10: UniProt Consortium (2010). "UniProt version 2010-11 released on 2010-11-02 00:00:00." Database.

UniProt11a: UniProt Consortium (2011). "UniProt version 2011-06 released on 2011-06-30 00:00:00." Database.

UniProt14: UniProt Consortium (2014). "UniProt version 2014-01 released on 2014-01-01 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 MetaCyc: Caspi et al, Nucleic Acids Research 42:D459-D471 2014
Page generated by SRI International Pathway Tools version 18.5 on Tue Nov 25, 2014, BIOCYC14B.