Schultz et al. (1998) Proc. Natl. Acad. Sci. USA 95, 5857-5864
Letunic et al. (2012) Nucleic Acids Res , doi:10.1093/nar/gkr931

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AICARFT_IMPCHas AICARFT/IMPCHase bienzyme

SMART accession number:	SM00798
Description:	This is a family of bifunctional enzymes catalysing the last two steps in de novo purine biosynthesis. The bifunctional enzyme is found in both prokaryotes and eukaryotes. The second last step is catalysed by 5-aminoimidazole-4-carboxamide ribonucleotide formyltransferase (AICARFT), this enzyme catalyses the formylation of AICAR with 10-formyl-tetrahydrofolate to yield FAICAR and tetrahydrofolate. The last step is catalysed by IMP (Inosine monophosphate) cyclohydrolase (IMPCHase), cyclizing FAICAR (5-formylaminoimidazole-4-carboxamide ribonucleotide) to IMP.
Interpro abstract (IPR002695):	This is a family of bifunctional enzymes catalysing the last two steps in de novo purine biosynthesis. The bifunctional enzyme is found in both prokaryotes and eukaryotes. The second last step is catalysed by 5-aminoimidazole-4-carboxamide ribonucleotide formyltransferase EC 2.1.2.3 (AICARFT), this enzyme catalyses the formylation of AICAR with 10-formyl-tetrahydrofolate to yield FAICAR and tetrahydrofolate [(PUBMED:9332377)]. The last step is catalysed by IMP (Inosine monophosphate) cyclohydrolase EC 3.5.4.10 (IMPCHase), cyclizing FAICAR (5-formylaminoimidazole-4-carboxamide ribonucleotide) to IMP [(PUBMED:9332377)].
GO process:	purine nucleotide biosynthetic process (GO:0006164)
GO function:	phosphoribosylaminoimidazolecarboxamide formyltransferase activity (GO:0004643), IMP cyclohydrolase activity (GO:0003937)
Family alignment:	View or CHROMA formatCLUSTALW formatMSF formatFASTA formatPIR format

There are 1868 AICARFT_IMPCHas domains in 1868 proteins in SMART's nrdb database.

Click on the following links for more information.

• Evolution (species in which this domain is found)

• Click on to expand nodes. To display all proteins with a AICARFT_IMPCHas domain in a specific node, click on it.

  This tree shows only several representative species. The complete taxonomic breakdown of all proteins with AICARFT_IMPCHas domain is also avaliable.

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  Go to specific node: Anopheles gambiae, Arabidopsis thaliana, Caenorhabditis elegans, Drosophila melanogaster, Homo sapiens, Mus musculus, Rattus norvegicus, Saccharomyces cerevisiae, Takifugu rubripes

• Cellular role (predicted cellular role)

• Cellular role: metabolism
  Binding / catalysis: This is a family of bifunctional enzymes catalysing the last two steps in de novo purine biosynthesis.

• Literature (relevant references for this domain)

• Primary literature is listed below; Automatically-derived, secondary literature is also avaliable.

  • Akira T et al.
  • Molecular cloning and expression of a rat cDNA encoding 5-aminoimidazole-4-carboxamide ribonucleotide formyltransferase/IMP cyclohydrolase.
  • Gene. 1997; 197: 289-93
  • Display abstract

  • The cDNA of a 5-aminoimidazole-4-carboxamide ribonucleotide formyltransferase/IMP cyclohydrolase (AICARFT/IMPCHase) was isolated from rat liver RNA by reverse transcription and the polymerase chain reaction (PCR). The rat AICARFT/IMPCHase cDNA included 1928 bp containing a coding region of 1779 bp for a 592-amino acid polypeptide (Mr = 64 200). Rat and human AICARFT/IMPCHase cDNAs show 84 and 91% homology at the nucleotide and amino acid sequence level, respectively. The protein produced by the rat cDNA using pET-expression system catalysed the penultimate and final steps of de novo purine biosynthesis. Northern analysis identified a 2.8-kb AICARFT/IMPCHase mRNA and the level of the AICARFT/IMPCHase transcripts increased markedly at 24 h after partial (70%) hepatectomy.

  • Rayl EA, Moroson BA, Beardsley GP
  • The human purH gene product, 5-aminoimidazole-4-carboxamide ribonucleotide formyltransferase/IMP cyclohydrolase. Cloning, sequencing, expression, purification, kinetic analysis, and domain mapping.
  • J Biol Chem. 1996; 271: 2225-33
  • Display abstract

  • We report here the cloning and sequencing of the cDNA, purification, steady state kinetic analysis, and truncation mapping studies of the human 5-aminoimidazole- 4-carboxamide ribonucleotide formyltransferase/IMP cyclohydrolase (AICARFT/IMPCHase). These steps of de novo purine biosynthesis, respectively. In all species of both prokaryotes and eukaryotes studied, these two activities are present on a single bifunctional polypeptide encoded on the purH gene. The human purH cDNA is 1776 base pairs in length encoding for a 591-amino acid polypeptic (Mr = 64,425). The human and avian purH cDNAs are 75 and 81% similar on the nucleotide and amino acid sequence level, respectively. The Km values for AICAR and (6R,6S)10-formyltetrahydrofolate are 16.8 microM +/- 1.5 and 60.2 microM +/- 5.0, respectively, for the cloned, purified human enzyme. A 10-amino acid sequence within the COOH-terminal portion of human AICARFT/IMPCHase has some degree of homology to a previously noted "folate binding site." Site directed mutagenesis studies indicate that this sequence plays no role in enzymatic activity. We have constructed truncation mutants which demonstrate that each of the two enzyme activities can be expressed independent of the other. IMPCHase and AICARFT activities are located within the NH2-terminal 223 and COOH-terminal 406 amino acids, respectively. The truncation mutant possessing AICARFT activity displays steady state kinetic parameters identical to those of the holoenzyme.

• Metabolism (metabolic pathways involving proteins which contain this domain)

• Click the image to view the interactive version of the map in iPath

  % proteins involved KEGG pathway ID Description 51.65 map00230 Purine metabolism 48.35 map00670 One carbon pool by folate This information is based on mapping of SMART genomic protein database to KEGG orthologous groups. Percentage points are related to the number of proteins with AICARFT_IMPCHas domain which could be assigned to a KEGG orthologous group, and not all proteins containing AICARFT_IMPCHas domain. Please note that proteins can be included in multiple pathways, ie. the numbers above will not always add up to 100%.

• Structure (3D structures containing this domain)

• 3D Structures of AICARFT_IMPCHas domains in PDB

  PDB code	Main view	Title
  1g8m		Crystal structure of avian atic, a bifunctional transformylase and cyclohydrolase enzyme in purine biosynthesis at 1.75 ang. resolution
  1m9n		Crystal structure of the homodimeric bifunctional transformylase and cyclohydrolase enzyme avian atic in complex with aicar and xmp at 1.93 angstroms.
  1oz0		Crystal structure of the homodimeric bifunctional transformylase and cyclohydrolase enzyme avian atic in complex with a multisubstrate adduct inhibitor beta-dadf.
  1p4r		Crystal structure of human atic in complex with folate- based inhibitor bw1540u88ud
  1pkx		Crystal structure of human atic in complex with xmp
  1pl0		Crystal structure of human atic in complex with folate- based inhibitor, bw2315u89uc
  1thz		Crystal structure of avian aicar transformylase in complex with a novel inhibitor identified by virtual ligand screening
  1zcz		Crystal structure of phosphoribosylaminoimidazolecarboxamide formyltransferase / imp cyclohydrolase (tm1249) from thermotoga maritima at 1.88 a resolution
  2b1g		Crystal structures of transition state analogue inhibitors of inosine monophosphate cyclohydrolase
  2b1i		Crystal structures of transition state analogue inhibitors of inosine monophosphate cyclohydrolase
  2iu0		Crystal structures of transition state analogue inhibitors of inosine monophosphate cyclohydrolase
  2iu3		Crystal structures of transition state analogue inhibitors of inosine monophosphate cyclohydrolase

• Links (links to other resources describing this domain)

• PFAM	AICARFT_IMPCHas
  INTERPRO	IPR002695

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