ID   FOLB_STAAU              Reviewed;         121 AA.
AC   P56740;
DT   30-MAY-2000, integrated into UniProtKB/Swiss-Prot.
DT   30-MAY-2000, sequence version 1.
DT   27-MAR-2024, entry version 107.
DE   RecName: Full=Dihydroneopterin aldolase {ECO:0000303|PubMed:9586996};
DE            Short=DHNA {ECO:0000303|PubMed:9586996};
DE            EC=4.1.2.25 {ECO:0000269|PubMed:9586996};
DE   AltName: Full=7,8-dihydroneopterin 2'-epimerase;
DE   AltName: Full=7,8-dihydroneopterin aldolase;
DE   AltName: Full=7,8-dihydroneopterin epimerase;
DE            EC=5.1.99.8 {ECO:0000250|UniProtKB:P0AC16};
DE   AltName: Full=Dihydroneopterin epimerase;
GN   Name=folB;
OS   Staphylococcus aureus.
OC   Bacteria; Bacillota; Bacilli; Bacillales; Staphylococcaceae;
OC   Staphylococcus.
OX   NCBI_TaxID=1280;
RN   [1]
RP   X-RAY CRYSTALLOGRAPHY (1.65 ANGSTROMS) OF APOENZYME AND IN COMPLEX WITH
RP   6-HYDROXYMETHYL-7,8-DIHYDRONEOPTERIN, FUNCTION, CATALYTIC ACTIVITY,
RP   BIOPHYSICOCHEMICAL PROPERTIES, REACTION MECHANISM, ACTIVE SITE, AND
RP   SUBUNIT.
RC   STRAIN=ATCC 25923 / DSM 1104 / JCM 2413 / NBRC 14462 / NCIMB 12702 /
RC   NCTC 12981 / Seattle 1945;
RX   PubMed=9586996; DOI=10.1038/nsb0598-357;
RA   Hennig M., D'Arcy A., Hampele I.C., Page M.G., Oefner C., Dale G.E.;
RT   "Crystal structure and reaction mechanism of 7,8-dihydroneopterin aldolase
RT   from Staphylococcus aureus.";
RL   Nat. Struct. Biol. 5:357-362(1998).
RN   [2]
RP   X-RAY CRYSTALLOGRAPHY (2.00 ANGSTROMS) IN COMPLEXES WITH
RP   7,8-DIHYDRONEOPTERIN ANALOGS.
RX   PubMed=15027862; DOI=10.1021/jm030497y;
RA   Sanders W.J., Nienaber V.L., Lerner C.G., McCall J.O., Merrick S.M.,
RA   Swanson S.J., Harlan J.E., Stoll V.S., Stamper G.F., Betz S.F.,
RA   Condroski K.R., Meadows R.P., Severin J.M., Walter K.A., Magdalinos P.,
RA   Jakob C.G., Wagner R., Beutel B.A.;
RT   "Discovery of potent inhibitors of dihydroneopterin aldolase using
RT   CrystaLEAD high-throughput X-ray crystallographic screening and structure-
RT   directed lead optimization.";
RL   J. Med. Chem. 47:1709-1718(2004).
RN   [3]
RP   X-RAY CRYSTALLOGRAPHY (1.68 ANGSTROMS) IN COMPLEXES WITH D-MONAPTERIN AND
RP   L-NEOPTERIN, FUNCTION, REACTION MECHANISM, AND ACTIVE SITE.
RX   PubMed=17331536; DOI=10.1016/j.jmb.2007.02.009;
RA   Blaszczyk J., Li Y., Gan J., Yan H., Ji X.;
RT   "Structural basis for the aldolase and epimerase activities of
RT   Staphylococcus aureus dihydroneopterin aldolase.";
RL   J. Mol. Biol. 368:161-169(2007).
CC   -!- FUNCTION: Catalyzes the conversion of 7,8-dihydroneopterin to 6-
CC       hydroxymethyl-7,8-dihydropterin. Can also catalyze the epimerization of
CC       carbon 2' of dihydroneopterin to dihydromonapterin.
CC       {ECO:0000269|PubMed:17331536, ECO:0000269|PubMed:9586996}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=7,8-dihydroneopterin = 6-hydroxymethyl-7,8-dihydropterin +
CC         glycolaldehyde; Xref=Rhea:RHEA:10540, ChEBI:CHEBI:17001,
CC         ChEBI:CHEBI:17071, ChEBI:CHEBI:44841; EC=4.1.2.25;
CC         Evidence={ECO:0000269|PubMed:9586996};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=7,8-dihydroneopterin = 7,8-dihydromonapterin;
CC         Xref=Rhea:RHEA:45328, ChEBI:CHEBI:17001, ChEBI:CHEBI:71175;
CC         EC=5.1.99.8; Evidence={ECO:0000250|UniProtKB:P0AC16};
CC   -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC       pH dependence:
CC         Optimum pH is 9.5. {ECO:0000269|PubMed:9586996};
CC   -!- PATHWAY: Cofactor biosynthesis; tetrahydrofolate biosynthesis; 2-amino-
CC       4-hydroxy-6-hydroxymethyl-7,8-dihydropteridine diphosphate from 7,8-
CC       dihydroneopterin triphosphate: step 3/4.
CC   -!- SUBUNIT: Homooctamer. Four molecules assemble into a ring, and two
CC       rings come together to give a cylinder with a hole of at least 13 a
CC       diameter. {ECO:0000269|PubMed:9586996}.
CC   -!- SIMILARITY: Belongs to the DHNA family. {ECO:0000305}.
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DR   RefSeq; WP_001154303.1; NZ_WKIS01000026.1.
DR   PDB; 1DHN; X-ray; 1.65 A; A=1-121.
DR   PDB; 1RRI; X-ray; 2.00 A; A=1-121.
DR   PDB; 1RRW; X-ray; 2.21 A; A=1-121.
DR   PDB; 1RRY; X-ray; 2.70 A; A=1-121.
DR   PDB; 1RS2; X-ray; 2.31 A; A=1-121.
DR   PDB; 1RS4; X-ray; 2.70 A; A=1-121.
DR   PDB; 1RSD; X-ray; 2.50 A; A=1-121.
DR   PDB; 1RSI; X-ray; 2.20 A; A=1-121.
DR   PDB; 1U68; X-ray; 2.40 A; A=1-121.
DR   PDB; 2DHN; X-ray; 2.20 A; A=1-121.
DR   PDB; 2NM2; X-ray; 1.70 A; A/B/C/D=1-121.
DR   PDB; 2NM3; X-ray; 1.68 A; A=1-121.
DR   PDBsum; 1DHN; -.
DR   PDBsum; 1RRI; -.
DR   PDBsum; 1RRW; -.
DR   PDBsum; 1RRY; -.
DR   PDBsum; 1RS2; -.
DR   PDBsum; 1RS4; -.
DR   PDBsum; 1RSD; -.
DR   PDBsum; 1RSI; -.
DR   PDBsum; 1U68; -.
DR   PDBsum; 2DHN; -.
DR   PDBsum; 2NM2; -.
DR   PDBsum; 2NM3; -.
DR   AlphaFoldDB; P56740; -.
DR   BMRB; P56740; -.
DR   SMR; P56740; -.
DR   ChEMBL; CHEMBL3217378; -.
DR   DrugBank; DB01906; 3-(5-amino-7-hydroxy-(1,2,3)triazolo(4,5-d)pyrimidin-2-yl)benzoic acid.
DR   DrugBank; DB03571; 3-(5-amino-7-hydroxy-[1,2,3]triazolo[4,5-d]pyrimidin-2-yl)-N-(3,5-dichlorobenzyl)-benzamide.
DR   DrugBank; DB03231; 3-(5-Amino-7-oxo-3,7-dihydro-2H-[1,2,3]triazolo[4,5-d]pyrimidin-2-yl)-N-(2-{[2-(hydroxymethyl)phenyl]sulfanyl}benzyl)benzamide.
DR   DrugBank; DB02119; 6-Hydroxymethyl-7,8-Dihydropterin.
DR   DrugBank; DB04425; 7,8-Dihydroneopterin.
DR   DrugBank; DB01778; 8-Aminotheophylline.
DR   DrugBank; DB02489; 9-Methylguanine.
DR   DrugBank; DB04168; Bropirimine.
DR   DrugBank; DB06906; ethyl 2-amino-4-hydroxypyrimidine-5-carboxylate.
DR   DrugBank; DB04400; L-erythro-7,8-dihydrobiopterin.
DR   OMA; GHYKSVA; -.
DR   BRENDA; 4.1.2.25; 3352.
DR   BRENDA; 5.1.99.8; 3352.
DR   UniPathway; UPA00077; UER00154.
DR   EvolutionaryTrace; P56740; -.
DR   GO; GO:0004150; F:dihydroneopterin aldolase activity; IEA:UniProtKB-EC.
DR   GO; GO:0016853; F:isomerase activity; IEA:UniProtKB-KW.
DR   GO; GO:0046656; P:folic acid biosynthetic process; IEA:UniProtKB-KW.
DR   GO; GO:0046654; P:tetrahydrofolate biosynthetic process; IEA:UniProtKB-UniPathway.
DR   CDD; cd00534; DHNA_DHNTPE; 1.
DR   Gene3D; 3.30.1130.10; -; 1.
DR   InterPro; IPR006156; Dihydroneopterin_aldolase.
DR   InterPro; IPR006157; FolB_dom.
DR   InterPro; IPR043133; GTP-CH-I_C/QueF.
DR   NCBIfam; TIGR00525; folB; 1.
DR   NCBIfam; TIGR00526; folB_dom; 1.
DR   PANTHER; PTHR42844; DIHYDRONEOPTERIN ALDOLASE 1-RELATED; 1.
DR   PANTHER; PTHR42844:SF1; DIHYDRONEOPTERIN ALDOLASE 1-RELATED; 1.
DR   Pfam; PF02152; FolB; 1.
DR   SMART; SM00905; FolB; 1.
DR   SUPFAM; SSF55620; Tetrahydrobiopterin biosynthesis enzymes-like; 1.
PE   1: Evidence at protein level;
KW   3D-structure; Folate biosynthesis; Isomerase; Lyase.
FT   CHAIN           1..121
FT                   /note="Dihydroneopterin aldolase"
FT                   /id="PRO_0000168283"
FT   ACT_SITE        100
FT                   /note="Proton donor/acceptor"
FT                   /evidence="ECO:0000305|PubMed:17331536,
FT                   ECO:0000305|PubMed:9586996"
FT   BINDING         22
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000305|PubMed:17331536,
FT                   ECO:0000305|PubMed:9586996, ECO:0007744|PDB:2NM2"
FT   BINDING         54
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000305|PubMed:17331536,
FT                   ECO:0000305|PubMed:9586996, ECO:0007744|PDB:2NM2"
FT   BINDING         73..74
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000305|PubMed:17331536,
FT                   ECO:0000305|PubMed:9586996, ECO:0007744|PDB:2NM2"
FT   STRAND          4..14
FT                   /evidence="ECO:0007829|PDB:1DHN"
FT   STRAND          17..19
FT                   /evidence="ECO:0007829|PDB:1DHN"
FT   HELIX           20..25
FT                   /evidence="ECO:0007829|PDB:1DHN"
FT   STRAND          27..37
FT                   /evidence="ECO:0007829|PDB:1DHN"
FT   HELIX           40..45
FT                   /evidence="ECO:0007829|PDB:1DHN"
FT   HELIX           48..50
FT                   /evidence="ECO:0007829|PDB:1DHN"
FT   HELIX           54..65
FT                   /evidence="ECO:0007829|PDB:1DHN"
FT   STRAND          66..68
FT                   /evidence="ECO:0007829|PDB:2NM2"
FT   HELIX           73..87
FT                   /evidence="ECO:0007829|PDB:1DHN"
FT   STRAND          91..102
FT                   /evidence="ECO:0007829|PDB:1DHN"
FT   STRAND          112..119
FT                   /evidence="ECO:0007829|PDB:1DHN"
SQ   SEQUENCE   121 AA;  13751 MW;  55B267FB69CA3D8D CRC64;
     MQDTIFLKGM RFYGYHGALS AENEIGQIFK VDVTLKVDLS EAGRTDNVID TVHYGEVFEE
     VKSIMEGKAV NLLEHLAERI ANRINSQYNR VMETKVRITK ENPPIPGHYD GVGIEIVREN
     K
//