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MetaCyc Enzyme: AICAR transformylase / IMP cyclohydrolase

Gene: purH Accession Numbers: EG10795 (MetaCyc), b4006, ECK3998

Species: Escherichia coli K-12 substr. MG1655

Summary:
In bacteria and eukaryotes the last two reactions of the de novo purine biosynthetic pathway for IMP biosynthesis are sequentially catalyzed by a bifunctional enzyme containing aminoimidazole carboxamide ribonucleotide (AICAR) transformylase and IMP cyclohydrolase activities. To date, much of the biochemical and structural characterization has been done on the enzyme from organisms other than E. coli (see for example [Wolan04, Axelrod08]).

In E. coli early studies suggested an association between AICAR transformylase and IMP cyclohydrolase [Gots69]. Later studies concluded that AICAR transformylase and IMP cyclohydrolase form a bifunctional enzyme with both activities residing on a single polypeptide [Aiba89, Flannigan90]. Complementation studies suggested that the N-terminal domain contains the IMP cyclohydrolase activity and the C-terminal domain contains the AICAR transformylase activity [Aiba89]. More recently recombinant, N-terminally His6-tagged enzyme from E. coli has been expressed, purified, crystallized, and subjected to preliminary X-ray diffraction analysis [Qiu11].

The transformylation reaction is the second of two such reactions in the de novo biosynthesis of purine nucleotides. Like the glycinamide ribonucleotide (GAR) transformylase, AICAR transformylase also utilizes 10-formyl-tetrahydrofolate as the formyl donor. The synthesis of IMP in both E. coli and Salmonella enterica subsp. enterica serovar Typhimurium is under the control of a common regulatory protein, the product of the purR gene [Flannigan90]. The final step in IMP biosynthesis is the ring closure of 5-formylamino-4-imidazolecarboxamide-ribonucleotide (FAICAR) to form IMP which is the first complete purine nucleotide.

Review: [Zhang08c]

Gene Citations: [Peterson91]

Locations: cytosol

Map Position: [4,203,966 <- 4,205,555]

Molecular Weight of Polypeptide: 57.329 kD (from nucleotide sequence)

Unification Links: ASAP:ABE-0013097 , CGSC:338 , EchoBASE:EB0788 , EcoGene:EG10795 , EcoliWiki:b4006 , ModBase:P15639 , OU-Microarray:b4006 , PortEco:purH , PR:PRO_000024869 , Pride:P15639 , Protein Model Portal:P15639 , RefSeq:NP_418434 , RegulonDB:EG10795 , SMR:P15639 , String:511145.b4006 , UniProt:P15639

Relationship Links: InterPro:IN-FAMILY:IPR002695 , InterPro:IN-FAMILY:IPR011607 , InterPro:IN-FAMILY:IPR016193 , InterPro:IN-FAMILY:IPR024051 , Panther:IN-FAMILY:PTHR11692 , Pfam:IN-FAMILY:PF01808 , Pfam:IN-FAMILY:PF02142 , Smart:IN-FAMILY:SM00798 , Smart:IN-FAMILY:SM00851

Gene-Reaction Schematic: ?

GO Terms:

Biological Process: GO:0042710 - biofilm formation Inferred from experiment [Garavaglia12]
GO:0006164 - purine nucleotide biosynthetic process Inferred by computational analysis [UniProtGOA11, GOA06, GOA01]
GO:0006189 - 'de novo' IMP biosynthetic process Inferred by computational analysis [UniProtGOA12]
GO:0008152 - metabolic process Inferred by computational analysis [UniProtGOA11]
Molecular Function: GO:0003937 - IMP cyclohydrolase activity Inferred from experiment Inferred by computational analysis [GOA06, GOA01a, GOA01, Aiba89]
GO:0004643 - phosphoribosylaminoimidazolecarboxamide formyltransferase activity Inferred from experiment Inferred by computational analysis [GOA06, GOA01a, GOA01, Aiba89]
GO:0003824 - catalytic activity Inferred by computational analysis [UniProtGOA11, GOA01]
GO:0016740 - transferase activity Inferred by computational analysis [UniProtGOA11]
GO:0016787 - hydrolase activity Inferred by computational analysis [UniProtGOA11]
Cellular Component: GO:0005829 - cytosol Inferred from experiment Inferred by computational analysis [DiazMejia09, Ishihama08, LopezCampistrou05]

MultiFun Terms: metabolism biosynthesis of building blocks nucleotides purine biosynthesis
metabolism central intermediary metabolism nucleotide and nucleoside conversions

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


Enzymatic reaction of: AICAR transformylase

Synonyms: aminoimidazole carboxamide ribonucleotide transformylase, 5'-phosphoribosyl 5-aminoimidazole-4-carboxamide transformylase

EC Number: 2.1.2.3

an N10-formyl-tetrahydrofolate + 5-amino-1-(5-phospho-D-ribosyl)imidazole-4-carboxamide <=> a tetrahydrofolate + 5-formamido-1-(5-phospho-D-ribosyl)-imidazole-4-carboxamide

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.

In Pathways: superpathway of histidine, purine, and pyrimidine biosynthesis , superpathway of purine nucleotides de novo biosynthesis II , inosine-5'-phosphate biosynthesis I

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

Summary:
Plasmids carrying an ORF encoding AICAR transformylase complemented E. coli mutant cells defective in this activity, as well as Salmonella enterica subsp. enterica serovar Typhimurium cells lacking IMP cyclohydrolase activity [Aiba89].


Enzymatic reaction of: IMP cyclohydrolase

EC Number: 3.5.4.10

IMP + H2O <=> 5-formamido-1-(5-phospho-D-ribosyl)-imidazole-4-carboxamide

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.

In Pathways: superpathway of histidine, purine, and pyrimidine biosynthesis , superpathway of purine nucleotides de novo biosynthesis II , inosine-5'-phosphate biosynthesis I

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

Summary:
Plasmids carrying an ORF encoding AICAR transformylase complemented E. coli mutant cells defective in this activity, as well as Salmonella enterica subsp. enterica serovar Typhimurium cells lacking IMP cyclohydrolase activity [Aiba89].


Sequence Features

Feature Class Location Citations Comment
Acetylation-Modification 287
[Zhang09, UniProt11]
UniProt: N6-acetyllysine.

History:
10/20/97 Gene b4006 from Blattner lab Genbank (v. M52) entry merged into EcoCyc gene EG10795; confirmed by SwissProt match.


References

Aiba89: Aiba A, Mizobuchi K (1989). "Nucleotide sequence analysis of genes purH and purD involved in the de novo purine nucleotide biosynthesis of Escherichia coli." J Biol Chem 1989;264(35);21239-46. PMID: 2687276

Axelrod08: Axelrod HL, McMullan D, Krishna SS, Miller MD, Elsliger MA, Abdubek P, Ambing E, Astakhova T, Carlton D, Chiu HJ, Clayton T, Duan L, Feuerhelm J, Grzechnik SK, Hale J, Han GW, Haugen J, Jaroszewski L, Jin KK, Klock HE, Knuth MW, Koesema E, Morse AT, Nigoghossian E, Okach L, Oommachen S, Paulsen J, Quijano K, Reyes R, Rife CL, van den Bedem H, Weekes D, White A, Wolf G, Xu Q, Hodgson KO, Wooley J, Deacon AM, Godzik A, Lesley SA, Wilson IA (2008). "Crystal structure of AICAR transformylase IMP cyclohydrolase (TM1249) from Thermotoga maritima at 1.88 A resolution." Proteins 71(2);1042-9. PMID: 18260100

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

Flannigan90: Flannigan KA, Hennigan SH, Vogelbacker HH, Gots JS, Smith JM (1990). "Purine biosynthesis in Escherichia coli K12: structure and DNA sequence studies of the purHD locus." Mol Microbiol 1990;4(3);381-92. PMID: 2192230

Garavaglia12: Garavaglia M, Rossi E, Landini P (2012). "The pyrimidine nucleotide biosynthetic pathway modulates production of biofilm determinants in Escherichia coli." PLoS One 7(2);e31252. PMID: 22359582

GOA01: GOA, DDB, FB, MGI, ZFIN (2001). "Gene Ontology annotation through association of InterPro records with GO terms."

GOA01a: GOA, MGI (2001). "Gene Ontology annotation based on Enzyme Commission mapping." Genomics 74;121-128.

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

Gots69: Gots JS, Dalal FR, Shumas SR (1969). "Genetic eparation of the inosinic acid cyclohydrolase-transformylase complex of Salmonella typhimurium." J Bacteriol 99(2);441-9. PMID: 4897111

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

LopezCampistrou05: Lopez-Campistrous A, Semchuk P, Burke L, Palmer-Stone T, Brokx SJ, Broderick G, Bottorff D, Bolch S, Weiner JH, Ellison MJ (2005). "Localization, annotation, and comparison of the Escherichia coli K-12 proteome under two states of growth." Mol Cell Proteomics 4(8);1205-9. PMID: 15911532

Peterson91: Peterson JW, Chopra AK, Prasad R (1991). "Fine mapping of the rrnE, purHD, and hydGH operons on the Escherichia coli chromosome." J Bacteriol 173(11);3274-5. PMID: 2045358

Qiu11: Qiu X, Yuan Y, Gao Y (2011). "Expression, purification, crystallization and preliminary X-ray diffraction crystallographic study of PurH from Escherichia coli." Acta Crystallogr Sect F Struct Biol Cryst Commun 67(Pt 12);1590-4. PMID: 22139174

UniProt11: UniProt Consortium (2011). "UniProt version 2011-06 released on 2011-06-30 00:00:00." Database.

UniProtGOA11: 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."

Wolan04: Wolan DW, Cheong CG, Greasley SE, Wilson IA (2004). "Structural insights into the human and avian IMP cyclohydrolase mechanism via crystal structures with the bound XMP inhibitor." Biochemistry 43(5);1171-83. PMID: 14756553

Zhang08c: Zhang Y, Morar M, Ealick SE (2008). "Structural biology of the purine biosynthetic pathway." Cell Mol Life Sci 65(23);3699-724. PMID: 18712276

Zhang09: Zhang J, Sprung R, Pei J, Tan X, Kim S, Zhu H, Liu CF, Grishin NV, Zhao Y (2009). "Lysine acetylation is a highly abundant and evolutionarily conserved modification in Escherichia coli." Mol Cell Proteomics 8(2);215-25. PMID: 18723842


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 Sun Nov 23, 2014, biocyc14.