FOLB_MYCTU
ID FOLB_MYCTU Reviewed; 133 AA.
AC P9WNC5; L0TG79; O06275; P0A580;
DT 16-APR-2014, integrated into UniProtKB/Swiss-Prot.
DT 16-APR-2014, sequence version 1.
DT 03-AUG-2022, entry version 41.
DE RecName: Full=Dihydroneopterin aldolase {ECO:0000303|PubMed:23150985};
DE Short=DHNA {ECO:0000303|PubMed:23150985};
DE EC=4.1.2.25 {ECO:0000269|PubMed:15876368, ECO:0000269|PubMed:23150985, ECO:0000269|PubMed:24855650};
DE AltName: Full=7,8-dihydroneopterin 2'-epimerase;
DE AltName: Full=7,8-dihydroneopterin aldolase {ECO:0000303|PubMed:15876368};
DE AltName: Full=7,8-dihydroneopterin epimerase;
DE EC=5.1.99.8 {ECO:0000269|PubMed:23150985};
DE AltName: Full=7,8-dihydroneopterin hydroxylase;
DE EC=1.13.11.81 {ECO:0000269|PubMed:23150985};
DE AltName: Full=Dihydroneopterin epimerase;
DE AltName: Full=Dihydroneopterin hydroxylase;
GN Name=folB {ECO:0000303|PubMed:15876368}; OrderedLocusNames=Rv3607c;
GN ORFNames=MTCY07H7B.15;
OS Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv).
OC Bacteria; Actinobacteria; Corynebacteriales; Mycobacteriaceae;
OC Mycobacterium; Mycobacterium tuberculosis complex.
OX NCBI_TaxID=83332;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=9634230; DOI=10.1038/31159;
RA Cole S.T., Brosch R., Parkhill J., Garnier T., Churcher C.M., Harris D.E.,
RA Gordon S.V., Eiglmeier K., Gas S., Barry C.E. III, Tekaia F., Badcock K.,
RA Basham D., Brown D., Chillingworth T., Connor R., Davies R.M., Devlin K.,
RA Feltwell T., Gentles S., Hamlin N., Holroyd S., Hornsby T., Jagels K.,
RA Krogh A., McLean J., Moule S., Murphy L.D., Oliver S., Osborne J.,
RA Quail M.A., Rajandream M.A., Rogers J., Rutter S., Seeger K., Skelton S.,
RA Squares S., Squares R., Sulston J.E., Taylor K., Whitehead S.,
RA Barrell B.G.;
RT "Deciphering the biology of Mycobacterium tuberculosis from the complete
RT genome sequence.";
RL Nature 393:537-544(1998).
RN [2]
RP IDENTIFICATION AS A DRUG TARGET [LARGE SCALE ANALYSIS].
RX PubMed=19099550; DOI=10.1186/1752-0509-2-109;
RA Raman K., Yeturu K., Chandra N.;
RT "targetTB: a target identification pipeline for Mycobacterium tuberculosis
RT through an interactome, reactome and genome-scale structural analysis.";
RL BMC Syst. Biol. 2:109-109(2008).
RN [3]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=21969609; DOI=10.1074/mcp.m111.011627;
RA Kelkar D.S., Kumar D., Kumar P., Balakrishnan L., Muthusamy B., Yadav A.K.,
RA Shrivastava P., Marimuthu A., Anand S., Sundaram H., Kingsbury R.,
RA Harsha H.C., Nair B., Prasad T.S., Chauhan D.S., Katoch K., Katoch V.M.,
RA Kumar P., Chaerkady R., Ramachandran S., Dash D., Pandey A.;
RT "Proteogenomic analysis of Mycobacterium tuberculosis by high resolution
RT mass spectrometry.";
RL Mol. Cell. Proteomics 10:M111.011627-M111.011627(2011).
RN [4]
RP FUNCTION, CATALYTIC ACTIVITY, SUBUNIT, MASS SPECTROMETRY, AND
RP BIOPHYSICOCHEMICAL PROPERTIES.
RX PubMed=23150985; DOI=10.1021/ja308350f;
RA Czekster C.M., Blanchard J.S.;
RT "One substrate, five products: reactions catalyzed by the dihydroneopterin
RT aldolase from Mycobacterium tuberculosis.";
RL J. Am. Chem. Soc. 134:19758-19771(2012).
RN [5]
RP FUNCTION, CATALYTIC ACTIVITY, SUBCELLULAR LOCATION, DOMAIN, AND MUTAGENESIS
RP OF 118-SER--VAL-133.
RC STRAIN=H37Rv;
RX PubMed=24855650; DOI=10.1074/jbc.m114.570119;
RA Contreras H., Joens M.S., McMath L.M., Le V.P., Tullius M.V., Kimmey J.M.,
RA Bionghi N., Horwitz M.A., Fitzpatrick J.A., Goulding C.W.;
RT "Characterization of a Mycobacterium tuberculosis nanocompartment and its
RT potential cargo proteins.";
RL J. Biol. Chem. 289:18279-18289(2014).
RN [6] {ECO:0007744|PDB:1NBU, ECO:0007744|PDB:1Z9W}
RP X-RAY CRYSTALLOGRAPHY (1.60 ANGSTROMS) OF 1-119 OF APOENZYME AND IN COMPLEX
RP WITH 6-HYDROXYMETHYL-7,8-DIHYDROPTERIN, FUNCTION, CATALYTIC ACTIVITY, AND
RP SUBUNIT.
RX PubMed=15876368; DOI=10.1016/j.jmb.2005.03.023;
RA Goulding C.W., Apostol M.I., Sawaya M.R., Phillips M., Parseghian A.,
RA Eisenberg D.;
RT "Regulation by oligomerization in a mycobacterial folate biosynthetic
RT enzyme.";
RL J. Mol. Biol. 349:61-72(2005).
CC -!- FUNCTION: Possible cargo protein of a type 1 encapsulin nanocompartment
CC involved in protection against oxidative stress (Probable). Catalyzes
CC the conversion of 7,8-dihydroneopterin to 6-hydroxymethyl-7,8-
CC dihydropterin, 7,8-dihydromonapterin and 7,8-dihydroxanthopterin,
CC respectively, in equal quantities. After longer incubation times the
CC only product is 6-hydroxymethyl-7,8-dihydropterin (PubMed:23150985,
CC PubMed:24855650). Retains aldolase activity when encapsulated with a
CC slight decrease in rate. It is not known if this protein is normally
CC found in the encapsulin nanocompartment (PubMed:24855650).
CC {ECO:0000269|PubMed:23150985, ECO:0000269|PubMed:24855650,
CC ECO:0000305|PubMed:24855650}.
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:15876368, ECO:0000269|PubMed:23150985,
CC ECO:0000269|PubMed:24855650};
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:0000269|PubMed:23150985};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=7,8-dihydroneopterin + O2 = 7,8-dihydroxanthopterin + formate
CC + glycolaldehyde + H(+); Xref=Rhea:RHEA:45332, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:15379, ChEBI:CHEBI:15740, ChEBI:CHEBI:17001,
CC ChEBI:CHEBI:17071, ChEBI:CHEBI:85130; EC=1.13.11.81;
CC Evidence={ECO:0000269|PubMed:23150985};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=0.165 uM for 7,8-dihydroneopterin in the aldolase reaction
CC {ECO:0000269|PubMed:23150985};
CC KM=0.154 uM for 7,8-dihydromonapterin in the aldolase reaction
CC {ECO:0000269|PubMed:23150985};
CC KM=0.154 uM for 7,8-dihydroneopterin in the epimerase reaction
CC {ECO:0000269|PubMed:23150985};
CC KM=0.154 uM for 7,8-dihydroneopterin in the oxygenase reaction
CC {ECO:0000269|PubMed:23150985};
CC Note=kcat is 0.0054 sec(-1) for the aldolase reaction with 7,8-
CC dihydroneopterin as substrate. kcat is 0.006 sec(-1) for the aldolase
CC reaction with 7,8-dihydromonapterin as substrate. kcat is 0.0015
CC sec(-1) for the epimerization of 7,8-dihydroneopterin. kcat is 0.0011
CC sec(-1) for the oxygenation reaction of 7,8-dihydroneopterin.
CC {ECO:0000269|PubMed:23150985};
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: Homotetramer in the absence of substrate. Homooctamer in the
CC presence of substrate. {ECO:0000269|PubMed:15876368,
CC ECO:0000269|PubMed:23150985}.
CC -!- SUBCELLULAR LOCATION: Encapsulin nanocompartment
CC {ECO:0000269|PubMed:24855650}. Note=Forms an approximately 6 nm
CC diameter cargo inside the encapsulin nanocompartment, would be similar
CC to the size of the homotetramer or homooctamer.
CC {ECO:0000305|PubMed:24855650}.
CC -!- DOMAIN: The C-terminus (residues 119-133) targets the protein to the
CC encapsulin nanocompartment. {ECO:0000269|PubMed:24855650}.
CC -!- MASS SPECTROMETRY: Mass=16585; Method=Electrospray;
CC Evidence={ECO:0000269|PubMed:23150985};
CC -!- MISCELLANEOUS: Was identified as a high-confidence drug target.
CC -!- MISCELLANEOUS: Cloning (to improve crystallization) removed residues
CC 121-133 which corresponds to the target-loading peptide for the
CC encapsulin nanocompartment. Target peptide removal does not change
CC enzyme activity. {ECO:0000269|PubMed:15876368}.
CC -!- SIMILARITY: Belongs to the DHNA family. {ECO:0000305}.
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DR EMBL; AL123456; CCP46430.1; -; Genomic_DNA.
DR PIR; H70955; H70955.
DR RefSeq; WP_003419537.1; NZ_NVQJ01000056.1.
DR RefSeq; YP_177996.1; NC_000962.3.
DR PDB; 1NBU; X-ray; 1.60 A; A/B/C/D/E/F/G/H=1-119.
DR PDB; 1Z9W; X-ray; 2.50 A; A=1-133.
DR PDBsum; 1NBU; -.
DR PDBsum; 1Z9W; -.
DR AlphaFoldDB; P9WNC5; -.
DR SMR; P9WNC5; -.
DR STRING; 83332.Rv3607c; -.
DR PaxDb; P9WNC5; -.
DR DNASU; 885345; -.
DR GeneID; 45427593; -.
DR GeneID; 885345; -.
DR KEGG; mtu:Rv3607c; -.
DR TubercuList; Rv3607c; -.
DR eggNOG; COG1539; Bacteria.
DR OMA; GHYKSVA; -.
DR PhylomeDB; P9WNC5; -.
DR BRENDA; 1.13.11.81; 3445.
DR BRENDA; 4.1.2.25; 3445.
DR UniPathway; UPA00077; UER00154.
DR Proteomes; UP000001584; Chromosome.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0004150; F:dihydroneopterin aldolase activity; IBA:GO_Central.
DR GO; GO:0016853; F:isomerase activity; IEA:UniProtKB-KW.
DR GO; GO:0016491; F:oxidoreductase 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 PANTHER; PTHR42844; PTHR42844; 1.
DR Pfam; PF02152; FolB; 1.
DR SMART; SM00905; FolB; 1.
DR TIGRFAMs; TIGR00525; folB; 1.
DR TIGRFAMs; TIGR00526; folB_dom; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Encapsulin nanocompartment; Folate biosynthesis; Isomerase;
KW Lyase; Oxidoreductase; Reference proteome.
FT CHAIN 1..133
FT /note="Dihydroneopterin aldolase"
FT /id="PRO_0000168275"
FT REGION 119..133
FT /note="Targeting peptide"
FT /evidence="ECO:0000269|PubMed:24855650"
FT ACT_SITE 99
FT /note="Proton donor/acceptor"
FT /evidence="ECO:0000250|UniProtKB:P56740, ECO:0000305"
FT BINDING 22
FT /ligand="substrate"
FT /evidence="ECO:0000305|PubMed:15876368,
FT ECO:0007744|PDB:1NBU"
FT BINDING 54
FT /ligand="substrate"
FT /evidence="ECO:0000305|PubMed:15876368,
FT ECO:0007744|PDB:1NBU"
FT BINDING 73..74
FT /ligand="substrate"
FT /evidence="ECO:0000305|PubMed:15876368,
FT ECO:0007744|PDB:1NBU"
FT MUTAGEN 118..133
FT /note="Missing: Protein no longer targeted to encapsulin
FT nanocompartments."
FT /evidence="ECO:0000269|PubMed:24855650"
FT STRAND 4..14
FT /evidence="ECO:0007829|PDB:1NBU"
FT HELIX 22..25
FT /evidence="ECO:0007829|PDB:1NBU"
FT STRAND 27..36
FT /evidence="ECO:0007829|PDB:1NBU"
FT HELIX 40..45
FT /evidence="ECO:0007829|PDB:1NBU"
FT HELIX 48..50
FT /evidence="ECO:0007829|PDB:1NBU"
FT HELIX 54..66
FT /evidence="ECO:0007829|PDB:1NBU"
FT STRAND 67..69
FT /evidence="ECO:0007829|PDB:1Z9W"
FT HELIX 73..85
FT /evidence="ECO:0007829|PDB:1NBU"
FT STRAND 92..98
FT /evidence="ECO:0007829|PDB:1NBU"
FT STRAND 105..107
FT /evidence="ECO:0007829|PDB:1NBU"
FT STRAND 109..118
FT /evidence="ECO:0007829|PDB:1NBU"
SQ SEQUENCE 133 AA; 14552 MW; B7BD7CD0D71AFB54 CRC64;
MADRIELRGL TVHGRHGVYD HERVAGQRFV IDVTVWIDLA EAANSDDLAD TYDYVRLASR
AAEIVAGPPR KLIETVGAEI ADHVMDDQRV HAVEVAVHKP QAPIPQTFDD VAVVIRRSRR
GGRGWVVPAG GAV
