MPTA_METJA
ID MPTA_METJA Reviewed; 313 AA.
AC Q58185;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT 05-MAY-2009, sequence version 2.
DT 03-AUG-2022, entry version 111.
DE RecName: Full=GTP cyclohydrolase MptA;
DE EC=3.5.4.39;
DE AltName: Full=GTP cyclohydrolase IV;
GN Name=mptA; OrderedLocusNames=MJ0775;
OS Methanocaldococcus jannaschii (strain ATCC 43067 / DSM 2661 / JAL-1 / JCM
OS 10045 / NBRC 100440) (Methanococcus jannaschii).
OC Archaea; Euryarchaeota; Methanomada group; Methanococci; Methanococcales;
OC Methanocaldococcaceae; Methanocaldococcus.
OX NCBI_TaxID=243232;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 43067 / DSM 2661 / JAL-1 / JCM 10045 / NBRC 100440;
RX PubMed=8688087; DOI=10.1126/science.273.5278.1058;
RA Bult C.J., White O., Olsen G.J., Zhou L., Fleischmann R.D., Sutton G.G.,
RA Blake J.A., FitzGerald L.M., Clayton R.A., Gocayne J.D., Kerlavage A.R.,
RA Dougherty B.A., Tomb J.-F., Adams M.D., Reich C.I., Overbeek R.,
RA Kirkness E.F., Weinstock K.G., Merrick J.M., Glodek A., Scott J.L.,
RA Geoghagen N.S.M., Weidman J.F., Fuhrmann J.L., Nguyen D., Utterback T.R.,
RA Kelley J.M., Peterson J.D., Sadow P.W., Hanna M.C., Cotton M.D.,
RA Roberts K.M., Hurst M.A., Kaine B.P., Borodovsky M., Klenk H.-P.,
RA Fraser C.M., Smith H.O., Woese C.R., Venter J.C.;
RT "Complete genome sequence of the methanogenic archaeon, Methanococcus
RT jannaschii.";
RL Science 273:1058-1073(1996).
RN [2]
RP FUNCTION, CATALYTIC ACTIVITY, SUBUNIT, COFACTOR, SUBSTRATE SPECIFICITY,
RP ACTIVITY REGULATION, REACTION MECHANISM, MUTAGENESIS OF GLU-47; HIS-98;
RP HIS-197; HIS-290 AND HIS-292, AND BIOPHYSICOCHEMICAL PROPERTIES.
RX PubMed=17497938; DOI=10.1021/bi700052a;
RA Grochowski L.L., Xu H., Leung K., White R.H.;
RT "Characterization of an Fe(2+)-dependent archaeal-specific GTP
RT cyclohydrolase, MptA, from Methanocaldococcus jannaschii.";
RL Biochemistry 46:6658-6667(2007).
CC -!- FUNCTION: Converts GTP to 7,8-dihydro-D-neopterin 2',3'-cyclic
CC phosphate, the first intermediate in the biosynthesis of coenzyme
CC methanopterin. It is also able to utilize a variety of GTP analogs as
CC substrates, including GDP, beta,gamma-methylene-GTP and GTP-[gamma-
CC thio]. {ECO:0000269|PubMed:17497938}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=GTP + H2O = 7,8-dihydroneopterin 2',3'-cyclic phosphate +
CC diphosphate + formate + H(+); Xref=Rhea:RHEA:25860,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15740,
CC ChEBI:CHEBI:33019, ChEBI:CHEBI:37565, ChEBI:CHEBI:58854; EC=3.5.4.39;
CC Evidence={ECO:0000269|PubMed:17497938};
CC -!- COFACTOR:
CC Name=Fe(2+); Xref=ChEBI:CHEBI:29033;
CC Evidence={ECO:0000269|PubMed:17497938};
CC Note=Binds 1 Fe(2+) ion per subunit. Mn(2+) and Zn(2+) can be used to a
CC lesser extent, but not at a relevant physiological concentration.
CC {ECO:0000269|PubMed:17497938};
CC -!- ACTIVITY REGULATION: Inhibited by GTP concentrations greater than 0.3
CC mM and by 2-amino-5-formylamino-6-ribofuranosylamino-4(3H)-pyrimidinone
CC 5'-phosphate (fapyGMP). Partial inhibition is observed when 2 mM GMP,
CC dGTP, or 7-methyl-GTP was included along with 2 mM GTP.
CC {ECO:0000269|PubMed:17497938}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC Vmax=13 nmol/min/mg enzyme with GDP as substrate (at pH 7.2)
CC {ECO:0000269|PubMed:17497938};
CC Vmax=30 nmol/min/mg enzyme with GTP as substrate (at pH 7.2)
CC {ECO:0000269|PubMed:17497938};
CC Vmax=39 nmol/min/mg enzyme with GTP-[gamma-thio] as substrate (at pH
CC 7.2) {ECO:0000269|PubMed:17497938};
CC Vmax=3 nmol/min/mg enzyme with beta,gamma-methylene-GTP as substrate
CC (at pH 7.2) {ECO:0000269|PubMed:17497938};
CC Note=Other purine nucleotides including ATP, ITP, dGTP, GMP, and 7-
CC methyl-GTP do not serve as substrates.;
CC pH dependence:
CC Optimum pH is 6.5. {ECO:0000269|PubMed:17497938};
CC Temperature dependence:
CC MptA loses 27% activity when it incubates for 10 min at 80 degrees
CC Celsius, 60% activity at 90 degrees Celsius, and 89% activity at 100
CC degrees Celsius. {ECO:0000269|PubMed:17497938};
CC -!- PATHWAY: Cofactor biosynthesis; 5,6,7,8-tetrahydromethanopterin
CC biosynthesis.
CC -!- SUBUNIT: Homodimer. {ECO:0000269|PubMed:17497938}.
CC -!- MISCELLANEOUS: MptA is the archetype of a new class of GTP
CC cyclohydrolases that catalyzes a series of reactions most similar to
CC that seen with GTPCHI but unique in that the cyclic phosphate is the
CC product.
CC -!- SIMILARITY: Belongs to the GTP cyclohydrolase IV family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAB98765.1; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR EMBL; L77117; AAB98765.1; ALT_INIT; Genomic_DNA.
DR PIR; G64396; G64396.
DR RefSeq; WP_064496622.1; NC_000909.1.
DR AlphaFoldDB; Q58185; -.
DR SMR; Q58185; -.
DR STRING; 243232.MJ_0775; -.
DR DNASU; 1451652; -.
DR EnsemblBacteria; AAB98765; AAB98765; MJ_0775.
DR GeneID; 1451652; -.
DR KEGG; mja:MJ_0775; -.
DR eggNOG; arCOG04301; Archaea.
DR HOGENOM; CLU_062816_1_0_2; -.
DR InParanoid; Q58185; -.
DR OMA; PCSQGMS; -.
DR OrthoDB; 109805at2157; -.
DR PhylomeDB; Q58185; -.
DR BioCyc; MetaCyc:MON-14599; -.
DR BRENDA; 3.5.4.39; 3260.
DR UniPathway; UPA00065; -.
DR Proteomes; UP000000805; Chromosome.
DR GO; GO:0044682; F:archaeal-specific GTP cyclohydrolase activity; IDA:MENGO.
DR GO; GO:0008198; F:ferrous iron binding; IDA:UniProtKB.
DR GO; GO:0003933; F:GTP cyclohydrolase activity; IBA:GO_Central.
DR GO; GO:0042802; F:identical protein binding; IDA:UniProtKB.
DR GO; GO:0042803; F:protein homodimerization activity; IDA:UniProtKB.
DR GO; GO:2001116; P:methanopterin-containing compound biosynthetic process; IDA:UniProtKB.
DR HAMAP; MF_01527_A; GTP_cyclohydrol_A; 1.
DR InterPro; IPR003801; GTP_cyclohydrolase_FolE2/MptA.
DR InterPro; IPR022840; GTP_cyclohydrolase_MptA.
DR PANTHER; PTHR36445; PTHR36445; 1.
DR Pfam; PF02649; GCHY-1; 1.
DR TIGRFAMs; TIGR00294; TIGR00294; 1.
PE 1: Evidence at protein level;
KW Hydrolase; Iron; Manganese; Metal-binding; Reference proteome; Zinc.
FT CHAIN 1..313
FT /note="GTP cyclohydrolase MptA"
FT /id="PRO_0000147743"
FT SITE 160
FT /note="May be catalytically important"
FT MUTAGEN 47
FT /note="E->D: Unchanged."
FT /evidence="ECO:0000269|PubMed:17497938"
FT MUTAGEN 98
FT /note="H->N: Unchanged."
FT /evidence="ECO:0000269|PubMed:17497938"
FT MUTAGEN 197
FT /note="H->N: Strong decrease in specific activity."
FT /evidence="ECO:0000269|PubMed:17497938"
FT MUTAGEN 290
FT /note="H->N: Strong decrease in specific activity."
FT /evidence="ECO:0000269|PubMed:17497938"
FT MUTAGEN 292
FT /note="H->N: Strong decrease in specific activity."
FT /evidence="ECO:0000269|PubMed:17497938"
SQ SEQUENCE 313 AA; 35873 MW; 4CCA67352C1773CF CRC64;
MNWRCDVQNF EPDVKISLTR VGVTNLKKLV RLKRTNKRPI ILLSTFEVFV NLPSSQKGIH
MSRNPEVIEG IIDEALELES YEMETICEEI VKRLFEKHEY ATEAEVFMVS DFMTKEKSPI
SGKYSQEIHK IMGGAKGIKK DDEIELTKIV GAEVVGITAC PCAQNLIKEI CIKNLKEKGF
SDEDIDKILD SVIFATHNQR GIGRIILEVP TGYDIEIMDI IEIIKKSMSA EIHGILKRAD
EAYVVEQSHK NPKFVEDCVR EMAKRVVEKF KHLPDETKVL IRQINMESIH RHDAFAEKVA
TLGELRRELL SYE
