SMART: FolB domain annotation

FolB Dihydroneopterin aldolase

SMART accession number:	SM00905
Description:	Dihydroneopterin aldolase catalyses the conversion of 7,8-dihydroneopterin to 6-hydroxymethyl-7,8-dihydropterin in the biosynthetic pathway of tetrahydrofolate. In the opportunistic pathogen Pneumocystis carinii, dihydroneopterin aldolase function is expressed as the N-terminal portion of the multifunctional folic acid synthesis protein (Fas). This region encompasses two domains, FasA and FasB, which are 27% amino acid identical. FasA and FasB also share significant amino acid sequence similarity with bacterial dihydroneopterin aldolases. This region consists of two tandem sequences each homologous to folB and which form tetramers (PUBMED:9709001).
Interpro abstract (IPR006157):	Dihydroneopterin aldolase catalyses the conversion of 7,8-dihydroneopterin to 6-hydroxymethyl-7,8-dihydropterin in the biosynthetic pathway of tetrahydrofolate. In the opportunistic pathogen Pneumocystis carinii, dihydroneopterin aldolase function is expressed as the N-terminal portion of the multifunctional folic acid synthesis protein (Fas). This region encompasses two domains, FasA and FasB, which are 27% amino acid identical. FasA and FasB also share significant amino acid sequence similarity with bacterial dihydroneopterin aldolases. This region consists of two tandem sequences each homologous to folB and which form tetramers [(PUBMED:9709001)].
GO process:	folic acid-containing compound metabolic process (GO:0006760)
GO function:	dihydroneopterin aldolase activity (GO:0004150)
Family alignment:	View or

There are 1454 FolB domains in 1423 proteins in SMART's nrdb database.

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Evolution (species in which this domain is found)
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Go to specific node: Arabidopsis thaliana, Saccharomyces cerevisiae
Cellular role (predicted cellular role)
Cellular role: metabolism
Literature (relevant references for this domain)
Primary literature is listed below; Automatically-derived, secondary literature is also avaliable.
- Haussmann C, Rohdich F, Schmidt E, Bacher A, Richter G
- Biosynthesis of pteridines in Escherichia coli. Structural and mechanisticsimilarity of dihydroneopterin-triphosphate epimerase and dihydroneopterinaldolase.
- J Biol Chem. 1998; 273: 17418-24
- Display abstract
- An open reading frame located at 69.0 kilobases on the Escherichia colichromosome was shown to code for dihydroneopterin aldolase, catalyzing theconversion of 7,8-dihydroneopterin to 6-hydroxymethyl-7,8-dihydropterin inthe biosynthetic pathway of tetrahydrofolate. The gene was subsequentlydesignated folB. The FolB protein shows 30% identity to the paralogousdihydroneopterin-triphosphate epimerase, which is specified by the folXgene located at 2427 kilobases on the E. coli chromosome. The folX andfolB gene products were both expressed to high yield in recombinant E.coli strains, and the recombinant proteins were purified to homogeneity.Both enzymes form homo-octamers. Aldolase can use L-threo-dihydroneopterinand D-erythro-dihydroneopterin as substrates for the formation of6-hydroxymethyldihydropterin, but it can also catalyze the epimerizationof carbon 2' of dihydroneopterin and dihydromonapterin at appreciablevelocity. Epimerase catalyzes the epimerization of carbon 2' in thetriphosphates of dihydroneopterin and dihydromonapterin. However, theenzyme can also catalyze the cleavage of the position 6 side chain ofseveral pteridine derivatives at a slow rate. Steady-state kineticparameters are reported for the various enzyme-catalyzed reactions. Wepropose that the polarization of the 2'-hydroxy group of the substratecould serve as the initial reaction step for the aldolase as well as forthe epimerase activity. A deletion mutant obtained by targeting the folXgene of E. coli has normal growth properties on complete medium as well ason minimal medium. Thus, the physiological role of the E. coli epimeraseremains unknown. The open reading frame ygiG of Hemophilus influenzaespecifies a protein with the catalytic properties of an aldolase. However,the genome of H. influenzae does not specify adihydroneopterin-triphosphate epimerase.
- Thomas MC, Ballantine SP, Bethell SS, Bains S, Kellam P, Delves CJ
- Single amino acid substitutions disrupt tetramer formation in thedihydroneopterin aldolase enzyme of Pneumocystis carinii.
- Biochemistry. 1998; 37: 11629-36
- Display abstract
- In the opportunistic pathogen Pneumocystis carinii, dihydroneopterinaldolase function is expressed as the N-terminal portion of themultifunctional folic acid synthesis protein (Fas). This regionencompasses two domains, FasA and FasB, which are 27% amino acididentical. FasA and FasB also share significant amino acid sequencesimilarity with bacterial dihydroneopterin aldolases. In the presentstudy, this enzyme function has been overproduced as an independentmonofunctional activity in Escherichia coli. Recombinant FasAB-Met23(amino acids 23-290 of the predicted open reading frame) was purified andshown to contain dihydroneopterin aldolase activity. The nativeFasAB-Met23 is a tetramer of the 30-kDa subunit, demonstratingcharacteristics of an associating-dissociating equilibrium system in whichonly the multimeric form of the enzyme is active. Multiple sequencealignment of FasA and FasB with other dihydroneopterin aldolaseshighlights only three positions where the amino acid is invariable betweenall the predicted proteins. The role of these conserved amino acidresidues in enzyme function was investigated using site-directedmutagenesis. Mutant FasAB-Met23 species were overproduced and purified tonear homogeneity. Three FasA domain mutants and two FasB domain mutantshad little or no detectable dihydroneopterin aldolase activity,implicating both FasA and FasB in the catalytic mechanism. We show thateach mutant protein containing an inactivating amino acid substitution haslost its ability to form stable tetramers.
Structure (3D structures containing this domain)

Links (links to other resources describing this domain)
PFAM FolB
INTERPRO IPR006157

PDB code	Main view	Title
1b9l		7,8-dihydroneopterin triphosphate epimerase
1dhn		1.65 angstrom resolution structure of 7,8-dihydroneopterin aldolase from staphylococcus aureus
1nbu		7,8-dihydroneopterin aldolase complexed with product from mycobacterium tuberculosis
1rri		Dhna complex with 3-(5-amino-7-hydroxy-[1,2,3] triazolo [4, 5-d]pyrimidin-2-yl)-benzoic acid
1rrw		Dhna complexed with 9-methylguanine
1rry		Dhna complexed with 2-amino-4-hydroxy-5- carboxyethylpyrimidine
1rs2		Dhna complex with 8-amino-1,3-dimethyl-3,7-dihydropurine-2, 6-dione
1rs4		Dhna, 7,8-dihydroneopterin aldolase complexed with 3-(5- amino-7-hydroxy-[1,2,3]triazolo[4,5-d]pyrimidin-2-yl)-n-(3, 5-dichlorobenzyl)-benzamide
1rsd		Dhna complex with 3-(5-amino-7-hydroxy-[1,2,3]triazolo[4,5- d]pyrimidin-2-yl)-n-[2-(2-hydroxymethyl-phenylsulfanyl)- benzyl]-benzamide
1rsi		Dhna complex with 2-amino-5-bromo-3-hydroxy-6- phenylpyrimidine
1sql		Crystal structure of 7,8-dihydroneopterin aldolase in complex with guanine
1u68		Dhna 7,8 dihydroneopterin complex
1z9w		Tetrameric structure of apo-7,8-dihydroneopterin aldolase from mycobacterium tuberculosis
2cg8		The bifunctional dihydroneopterin aldolase 6-hydroxymethyl- 7,8-dihydropterin synthase from streptococcus pneumoniae
2dhn		Complex of 7,8-dihydroneopterin aldolase from staphylococcus aureus with 6-hydroxymethyl-7,8- dihydropterin at 2.2 a resolution
2nm2		Crystal structure of dihydroneopterin aldolase from s. aureus in complex with (1s,2r)-neopterin at 1.50 angstrom resolution
2nm3		Crystal structure of dihydroneopterin aldolase from s. aureus in complex with (1s,2s)-monapterin at 1.68 angstrom resolution
2o90		Atomic resolution crystal structure of e.coli dihydroneopterin aldolase in complex with neopterin

PFAM	FolB
INTERPRO	IPR006157

FolB

3D Structures of FolB domains in PDB