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41  structures 4505  species 0  interactions 6712  sequences 64  architectures

Family: FTHFS (PF01268)

Summary: Formate--tetrahydrofolate ligase

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This is the Wikipedia entry entitled "Formate-tetrahydrofolate ligase". More...

Formate-tetrahydrofolate ligase Edit Wikipedia article

This page is based on a Wikipedia article. The text is available under the Creative Commons Attribution/Share-Alike License.

This is the Wikipedia entry entitled "Formate–tetrahydrofolate ligase". More...

Formate–tetrahydrofolate ligase Edit Wikipedia article

formate-tetrahydrofolate ligase
Identifiers
EC no.6.3.4.3
CAS no.9023-66-9
Databases
IntEnzIntEnz view
BRENDABRENDA entry
ExPASyNiceZyme view
KEGGKEGG entry
MetaCycmetabolic pathway
PRIAMprofile
PDB structuresRCSB PDB PDBe PDBsum
Gene OntologyAmiGO / QuickGO
Formate--tetrahydrofolate ligase
PDB 1eg7 EBI.jpg
the crystal structure of formyltetrahydrofolate synthetase from moorella thermoacetica
Identifiers
SymbolFTHFS
PfamPF01268
Pfam clanCL0023
InterProIPR000559
PROSITEPDOC00595
SCOP21fpm / SCOPe / SUPFAM

In enzymology, a formate-tetrahydrofolate ligase (EC 6.3.4.3) is an enzyme that catalyzes the chemical reaction

ATP + formate + tetrahydrofolate ADP + phosphate + 10-formyltetrahydrofolate

The 3 substrates of this enzyme are ATP, formate, and tetrahydrofolate, whereas its 3 products are ADP, phosphate, and 10-formyltetrahydrofolate.

This enzyme belongs to the family of ligases, specifically those forming generic carbon-nitrogen bonds. This enzyme participates in glyoxylate and dicarboxylate metabolism and one carbon pool by folate.

In eukaryotes the FTHFS activity is expressed by a multifunctional enzyme, C-1-tetrahydrofolate synthase (C1-THF synthase), which also catalyses the dehydrogenase and cyclohydrolase activities. Two forms of C1-THF synthases are known, one is located in the mitochondrial matrix, while the second one is cytoplasmic.[1] In both forms the FTHFS domain consists of about 600 amino acid residues and is located in the C-terminal section of C1-THF synthase. In prokaryotes FTHFS activity is expressed by a monofunctional homotetrameric enzyme of about 560 amino acid residues.[2]

Nomenclature

The systematic name of this enzyme class is formate:tetrahydrofolate ligase (ADP-forming). Other names in common use include:

  • formyltetrahydrofolate synthetase,
  • 10-formyltetrahydrofolate synthetase,
  • tetrahydrofolic formylase, and
  • tetrahydrofolate formylase.

Examples

Human genes encoding formate-tetrahydrofolate ligases include:

Structural studies

As of late 2007, 3 structures have been solved for this class of enzymes, with PDB accession codes 1EG7, 1FP7, and 1FPM.

The crystal structure of N(10)-formyltetrahydrofolate synthetase from Moorella thermoacetica shows that the subunit is composed of three domains organised around three mixed beta-sheets. There are two cavities between adjacent domains. One of them was identified as the nucleotide binding site by homology modelling. The large domain contains a seven-stranded beta-sheet surrounded by helices on both sides. The second domain contains a five-stranded beta-sheet with two alpha-helices packed on one side while the other two are a wall of the active site cavity. The third domain contains a four-stranded beta-sheet forming a half-barrel. The concave side is covered by two helices while the convex side is another wall of the large cavity. Arg 97 is likely involved in formyl phosphate binding. The tetrameric molecule is relatively flat with the shape of the letter X, and the active sites are located at the end of the subunits far from the subunit interface.[3]

Related enzymes

The reverse reaction converting 10-formyltetrahydrofolate to tetrahydrofolate is performed by formyltetrahydrofolate dehydrogenase.

References

  1. ^ Shannon KW, Rabinowitz JC (June 1988). "Isolation and characterization of the Saccharomyces cerevisiae MIS1 gene encoding mitochondrial C1-tetrahydrofolate synthase". J. Biol. Chem. 263 (16): 7717–25. PMID 2836393.
  2. ^ Lovell CR, Przybyla A, Ljungdahl LG (June 1990). "Primary structure of the thermostable formyltetrahydrofolate synthetase from Clostridium thermoaceticum". Biochemistry. 29 (24): 5687–94. doi:10.1021/bi00476a007. PMID 2200509.
  3. ^ Radfar R, Shin R, Sheldrick GM, Minor W, Lovell CR, Odom JD, Dunlap RB, Lebioda L (April 2000). "The crystal structure of N(10)-formyltetrahydrofolate synthetase from Moorella thermoacetica". Biochemistry. 39 (14): 3920–6. doi:10.1021/bi992790z. PMID 10747779.

Further reading

  • JAENICKE L, BRODE E (1961). "[Research on monocarbon compounds. I. The tetrahydrofolate formylase from pigeon liver. Purification and mechanism.]". Biochem. Z. 334: 108–32. PMID 13789141.
  • Long CW; Levitzki A; Houston LL; Koshland DE, Jr (1969). "Subunit structures and interactions of CTP synthetase". Fed. Proc. 28: 342.
  • RABINOWITZ JC, PRICER WE (1962). "Formyltetrahydrofolate synthetase. I. Isolation and crystallization of the enzyme". J. Biol. Chem. 237: 2898–902. PMID 14489619.
  • Whiteley HR, Osborn MJ, Huennekens FM (1959). "Purification and properties of the formate-activating enzyme from Micrococcus aerogenes". J. Biol. Chem. 234 (6): 1538–1543. PMID 13654413.
This article incorporates text from the public domain Pfam and InterPro: IPR000559


This page is based on a Wikipedia article. The text is available under the Creative Commons Attribution/Share-Alike License.

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Formate--tetrahydrofolate ligase Provide feedback

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Internal database links

External database links

This tab holds annotation information from the InterPro database.

InterPro entry IPR000559

Formate--tetrahydrofolate ligase ( EC ) (formyltetrahydrofolate synthetase) (FTHFS) is one of the enzymes participating in the transfer of one-carbon units, an essential element of various biosynthetic pathways. FTHFS catalyzes the ATP-dependent activation of formate ion via its addition to the N10 position of tetrahydrofolate. FTHFS is a highly expressed key enzyme in both the Wood-Ljungdahl pathway of autotrophic CO 2 fixation (acetogenesis) and the glycine synthase/reductase pathways of purinolysis. The key physiological role of this enzyme in acetogens is to catalyze the formylation of tetrahydrofolate, an initial step in the reduction of carbon dioxide and other one-carbon precursors to acetate. In purinolytic organisms, the enzymatic reaction is reversed, liberating formate from 10-formyltetrahydrofolate with concurrent production of ATP [ PUBMED:11087401 , PUBMED:10747779 ]. In many of these processes the transfers of one-carbon units are mediated by the coenzyme tetrahydrofolate (THF). In eukaryotes the FTHFS activity is expressed by a multifunctional enzyme, C-1-tetrahydrofolate synthase (C1-THF synthase), which also catalyses the dehydrogenase and cyclohydrolase activities. Two forms of C1-THF synthases are known [ PUBMED:2836393 ], one is located in the mitochondrial matrix, while the second one is cytoplasmic. In both forms the FTHFS domain consists of about 600 amino acid residues and is located in the C-terminal section of C1-THF synthase. In prokaryotes FTHFS activity is expressed by a monofunctional homotetrameric enzyme of about 560 amino acid residues [ PUBMED:2200509 ].

The crystal structure of N(10)-formyltetrahydrofolate synthetase from Moorella thermoacetica shows that the subunit is composed of three domains organised around three mixed beta-sheets. There are two cavities between adjacent domains. One of them was identified as the nucleotide binding site by homology modelling. The large domain contains a seven-stranded beta-sheet surrounded by helices on both sides. The second domain contains a five-stranded beta-sheet with two alpha-helices packed on one side while the other two are a wall of the active site cavity. The third domain contains a four-stranded beta-sheet forming a half-barrel. The concave side is covered by two helices while the convex side is another wall of the large cavity. Arg 97 is likely involved in formyl phosphate binding. The tetrameric molecule is relatively flat with the shape of the letter X, and the active sites are located at the end of the subunits far from the subunit interface [ PUBMED:10747779 ].

Gene Ontology

The mapping between Pfam and Gene Ontology is provided by InterPro. If you use this data please cite InterPro.

Domain organisation

Below is a listing of the unique domain organisations or architectures in which this domain is found. More...

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Pfam Clan

This family is a member of clan P-loop_NTPase (CL0023), which has the following description:

AAA family proteins often perform chaperone-like functions that assist in the assembly, operation, or disassembly of protein complexes [2].

The clan contains the following 245 members:

6PF2K AAA AAA-ATPase_like AAA_10 AAA_11 AAA_12 AAA_13 AAA_14 AAA_15 AAA_16 AAA_17 AAA_18 AAA_19 AAA_2 AAA_21 AAA_22 AAA_23 AAA_24 AAA_25 AAA_26 AAA_27 AAA_28 AAA_29 AAA_3 AAA_30 AAA_31 AAA_32 AAA_33 AAA_34 AAA_35 AAA_5 AAA_6 AAA_7 AAA_8 AAA_9 AAA_PrkA ABC_ATPase ABC_tran ABC_tran_Xtn Adeno_IVa2 Adenylsucc_synt ADK AFG1_ATPase AIG1 APS_kinase Arf ArsA_ATPase ATP-synt_ab ATP_bind_1 ATP_bind_2 ATPase ATPase_2 Bac_DnaA BCA_ABC_TP_C Beta-Casp bpMoxR BrxC_BrxD BrxL_ATPase Cas_Csn2 Cas_St_Csn2 CbiA CBP_BcsQ CDC73_C CENP-M CFTR_R CLP1_P CMS1 CoaE CobA_CobO_BtuR CobU cobW CPT CSM2 CTP_synth_N Cytidylate_kin Cytidylate_kin2 DAP3 DEAD DEAD_2 divDNAB DLIC DNA_pack_C DNA_pack_N DNA_pol3_delta DNA_pol3_delta2 DnaB_C dNK DO-GTPase1 DO-GTPase2 DUF1611 DUF2075 DUF2326 DUF2478 DUF257 DUF2813 DUF3584 DUF463 DUF4914 DUF5906 DUF6079 DUF815 DUF835 DUF87 DUF927 Dynamin_N Dynein_heavy Elong_Iki1 ELP6 ERCC3_RAD25_C Exonuc_V_gamma FeoB_N Fer4_NifH Flavi_DEAD FTHFS FtsK_SpoIIIE G-alpha Gal-3-0_sulfotr GBP GBP_C GpA_ATPase GpA_nuclease GTP_EFTU Gtr1_RagA Guanylate_kin GvpD_P-loop HDA2-3 Helicase_C Helicase_C_2 Helicase_C_4 Helicase_RecD HerA_C Herpes_Helicase Herpes_ori_bp Herpes_TK HydF_dimer HydF_tetramer Hydin_ADK IIGP IPPT IPT iSTAND IstB_IS21 KAP_NTPase KdpD Kinase-PPPase Kinesin KTI12 LAP1_C LpxK MCM MeaB MEDS Mg_chelatase Microtub_bd MipZ MMR_HSR1 MMR_HSR1_C MobB MukB Mur_ligase_M MutS_V Myosin_head NACHT NAT_N NB-ARC NOG1 NTPase_1 NTPase_P4 ORC3_N P-loop_TraG ParA Parvo_NS1 PAXNEB PduV-EutP PhoH PIF1 Ploopntkinase1 Ploopntkinase2 Ploopntkinase3 Podovirus_Gp16 Polyoma_lg_T_C Pox_A32 PPK2 PPV_E1_C PRK PSY3 Rad17 Rad51 Ras RecA ResIII RHD3_GTPase RhoGAP_pG1_pG2 RHSP RNA12 RNA_helicase Roc RsgA_GTPase RuvB_N SbcC_Walker_B SecA_DEAD Senescence Septin Sigma54_activ_2 Sigma54_activat SKI SMC_N SNF2-rel_dom SpoIVA_ATPase Spore_III_AA SRP54 SRPRB SulA Sulfotransfer_1 Sulfotransfer_2 Sulfotransfer_3 Sulfotransfer_4 Sulfotransfer_5 Sulphotransf SWI2_SNF2 T2SSE T4SS-DNA_transf TerL_ATPase Terminase_3 Terminase_6N Thymidylate_kin TIP49 TK TmcA_N TniB Torsin TraG-D_C tRNA_lig_kinase TrwB_AAD_bind TsaE UvrB UvrD-helicase UvrD_C UvrD_C_2 Viral_helicase1 VirC1 VirE YqeC Zeta_toxin Zot

Alignments

We store a range of different sequence alignments for families. As well as the seed alignment from which the family is built, we provide the full alignment, generated by searching the sequence database (reference proteomes) using the family HMM. We also generate alignments using four representative proteomes (RP) sets and the UniProtKB sequence database. More...

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We make a range of alignments for each Pfam-A family. You can see a description of each above. You can view these alignments in various ways but please note that some types of alignment are never generated while others may not be available for all families, most commonly because the alignments are too large to handle.

  Seed
(386)
Full
(6712)
Representative proteomes UniProt
(28571)
RP15
(1100)
RP35
(3210)
RP55
(6112)
RP75
(9257)
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  Seed
(386)
Full
(6712)
Representative proteomes UniProt
(28571)
RP15
(1100)
RP35
(3210)
RP55
(6112)
RP75
(9257)
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  Seed
(386)
Full
(6712)
Representative proteomes UniProt
(28571)
RP15
(1100)
RP35
(3210)
RP55
(6112)
RP75
(9257)
Raw Stockholm Download   Download   Download   Download   Download   Download   Download  
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You can also download a FASTA format file containing the full-length sequences for all sequences in the full alignment.

HMM logo

HMM logos is one way of visualising profile HMMs. Logos provide a quick overview of the properties of an HMM in a graphical form. You can see a more detailed description of HMM logos and find out how you can interpret them here. More...

Trees

This page displays the phylogenetic tree for this family's seed alignment. We use FastTree to calculate neighbour join trees with a local bootstrap based on 100 resamples (shown next to the tree nodes). FastTree calculates approximately-maximum-likelihood phylogenetic trees from our seed alignment.

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Curation and family details

This section shows the detailed information about the Pfam family. You can see the definitions of many of the terms in this section in the glossary and a fuller explanation of the scoring system that we use in the scores section of the help pages.

Curation View help on the curation process

Seed source: Prosite
Previous IDs: none
Type: Family
Sequence Ontology: SO:0100021
Author: Finn RD , Bateman A
Number in seed: 386
Number in full: 6712
Average length of the domain: 529.30 aa
Average identity of full alignment: 51 %
Average coverage of the sequence by the domain: 82.68 %

HMM information View help on HMM parameters

HMM build commands:
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 61295632 -E 1000 --cpu 4 HMM pfamseq
Model details:
Parameter Sequence Domain
Gathering cut-off 27.0 27.0
Trusted cut-off 27.0 27.2
Noise cut-off 26.9 26.9
Model length: 556
Family (HMM) version: 22
Download: download the raw HMM for this family

Species distribution

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Structures

For those sequences which have a structure in the Protein DataBank, we use the mapping between UniProt, PDB and Pfam coordinate systems from the PDBe group, to allow us to map Pfam domains onto UniProt sequences and three-dimensional protein structures. The table below shows the structures on which the FTHFS domain has been found. There are 41 instances of this domain found in the PDB. Note that there may be multiple copies of the domain in a single PDB structure, since many structures contain multiple copies of the same protein sequence.

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AlphaFold Structure Predictions

The list of proteins below match this family and have AlphaFold predicted structures. Click on the protein accession to view the predicted structure.

Protein Predicted structure External Information
A0A1D6I5L0 View 3D Structure Click here
A0A1D8PRL4 View 3D Structure Click here
A0A2R8RW82 View 3D Structure Click here
A0JZ10 View 3D Structure Click here
A0KIN9 View 3D Structure Click here
A0LLR3 View 3D Structure Click here
A0PXN0 View 3D Structure Click here
A1B1M8 View 3D Structure Click here
A1R8N9 View 3D Structure Click here
A1SAE2 View 3D Structure Click here
A1SQH3 View 3D Structure Click here
A2SKX8 View 3D Structure Click here
A2SS72 View 3D Structure Click here
A3CL27 View 3D Structure Click here
A3CN49 View 3D Structure Click here
A3DI22 View 3D Structure Click here
A3MZI4 View 3D Structure Click here
A3QA17 View 3D Structure Click here
A4FL80 View 3D Structure Click here
A4I5T5 View 3D Structure Click here
A4J0S6 View 3D Structure Click here
A4VU67 View 3D Structure Click here
A5G276 View 3D Structure Click here
A5I7P9 View 3D Structure Click here
A5N5B3 View 3D Structure Click here
A5UPV2 View 3D Structure Click here
A5VHS9 View 3D Structure Click here
A6L4P0 View 3D Structure Click here
A6LAR6 View 3D Structure Click here
A7GZZ0 View 3D Structure Click here
A7HLZ4 View 3D Structure Click here
A8F7D5 View 3D Structure Click here
A8FEC9 View 3D Structure Click here
A8H8Z4 View 3D Structure Click here
A8LIR1 View 3D Structure Click here
A8MIN1 View 3D Structure Click here
A8ZZJ0 View 3D Structure Click here
A9B4H8 View 3D Structure Click here
A9KNJ5 View 3D Structure Click here
A9NE95 View 3D Structure Click here