GLPX_MYCTU
ID GLPX_MYCTU Reviewed; 362 AA.
AC P9WN21; L0T8L8; O53447; Q7D8U9;
DT 16-APR-2014, integrated into UniProtKB/Swiss-Prot.
DT 16-APR-2014, sequence version 1.
DT 03-AUG-2022, entry version 42.
DE RecName: Full=Fructose-1,6-bisphosphatase class 2 {ECO:0000303|PubMed:15470127};
DE Short=FBPase class 2 {ECO:0000303|PubMed:15470127};
DE EC=3.1.3.11 {ECO:0000269|PubMed:15470127, ECO:0000269|PubMed:21451980};
DE AltName: Full=D-fructose-1,6-bisphosphate 1-phosphohydrolase class 2;
DE AltName: Full=Fructose 1,6-bisphosphatase II {ECO:0000303|PubMed:21451980};
GN Name=glpX {ECO:0000303|PubMed:21451980}; OrderedLocusNames=Rv1099c;
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 PROTEIN SEQUENCE OF 2-25.
RC STRAIN=H37Rv;
RX PubMed=34915127; DOI=10.1016/j.ygeno.2021.12.001;
RA Shi J., Meng S., Wan L., Zhang Z., Jiang S., Zhu H., Dai E., Chang L.,
RA Gao H., Wan K., Zhang L., Zhao X., Liu H., Lyu Z., Zhang Y., Xu P.;
RT "Deep N-terminomics of Mycobacterium tuberculosis H37Rv extensively correct
RT annotated encoding genes.";
RL Genomics 114:292-304(2021).
RN [3]
RP DISRUPTION PHENOTYPE.
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=14569030; DOI=10.1073/pnas.2134250100;
RA Sassetti C.M., Rubin E.J.;
RT "Genetic requirements for mycobacterial survival during infection.";
RL Proc. Natl. Acad. Sci. U.S.A. 100:12989-12994(2003).
RN [4]
RP FUNCTION, CATALYTIC ACTIVITY, KINETIC PARAMETERS, ACTIVITY REGULATION, AND
RP INDUCTION.
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=15470127; DOI=10.1099/mic.0.27204-0;
RA Movahedzadeh F., Rison S.C., Wheeler P.R., Kendall S.L., Larson T.J.,
RA Stoker N.G.;
RT "The Mycobacterium tuberculosis Rv1099c gene encodes a GlpX-like class II
RT fructose 1,6-bisphosphatase.";
RL Microbiology 150:3499-3505(2004).
RN [5]
RP IDENTIFICATION BY MASS SPECTROMETRY, DETERMINATION OF TRANSLATIONAL START
RP SITE, CLEAVAGE OF INITIATOR METHIONINE, AND ACETYLATION AT THR-2.
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=17259624; DOI=10.1099/mic.0.2006/001537-0;
RA Rison S.C., Mattow J., Jungblut P.R., Stoker N.G.;
RT "Experimental determination of translational starts using peptide mass
RT mapping and tandem mass spectrometry within the proteome of Mycobacterium
RT tuberculosis.";
RL Microbiology 153:521-528(2007).
RN [6]
RP FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, COFACTOR,
RP ACTIVITY REGULATION, AND SUBUNIT.
RC STRAIN=H37Rv;
RX PubMed=21451980; DOI=10.1007/s12010-011-9219-x;
RA Gutka H.J., Rukseree K., Wheeler P.R., Franzblau S.G., Movahedzadeh F.;
RT "glpX gene of Mycobacterium tuberculosis: heterologous expression,
RT purification, and enzymatic characterization of the encoded fructose 1,6-
RT bisphosphatase II.";
RL Appl. Biochem. Biotechnol. 164:1376-1389(2011).
RN [7]
RP CRYSTALLIZATION, AND SUBUNIT.
RC STRAIN=H37Rv;
RX PubMed=21636919; DOI=10.1107/s1744309111014722;
RA Gutka H.J., Franzblau S.G., Movahedzadeh F., Abad-Zapatero C.;
RT "Crystallization and preliminary X-ray characterization of the glpX-encoded
RT class II fructose-1,6-bisphosphatase from Mycobacterium tuberculosis.";
RL Acta Crystallogr. F 67:710-713(2011).
RN [8]
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 [9]
RP DISRUPTION PHENOTYPE, AND PATHWAY.
RC STRAIN=H37Rv;
RX PubMed=26258286; DOI=10.1038/ncomms8912;
RA Ganapathy U., Marrero J., Calhoun S., Eoh H., de Carvalho L.P., Rhee K.,
RA Ehrt S.;
RT "Two enzymes with redundant fructose bisphosphatase activity sustain
RT gluconeogenesis and virulence in Mycobacterium tuberculosis.";
RL Nat. Commun. 6:7912-7912(2015).
RN [10]
RP DISRUPTION PHENOTYPE.
RC STRAIN=H37Rv;
RX PubMed=26397812; DOI=10.1371/journal.pone.0138436;
RA Gutka H.J., Wang Y., Franzblau S.G., Movahedzadeh F.;
RT "glpx gene in Mycobacterium tuberculosis is required for in vitro
RT gluconeogenic growth and in vivo survival.";
RL PLoS ONE 10:E0138436-E0138436(2015).
CC -!- FUNCTION: Catalyzes the hydrolysis of fructose 1,6-bisphosphate to
CC fructose 6-phosphate (PubMed:15470127, PubMed:21451980). Seems to be
CC the major FBPase of M.tuberculosis and to play a key role in
CC gluconeogenesis for conversion of lipid carbon into cell wall glycans.
CC Does not display activity against inositol 1-phosphate
CC (PubMed:15470127). {ECO:0000269|PubMed:15470127,
CC ECO:0000269|PubMed:21451980}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=beta-D-fructose 1,6-bisphosphate + H2O = beta-D-fructose 6-
CC phosphate + phosphate; Xref=Rhea:RHEA:11064, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:32966, ChEBI:CHEBI:43474, ChEBI:CHEBI:57634; EC=3.1.3.11;
CC Evidence={ECO:0000269|PubMed:15470127, ECO:0000269|PubMed:21451980};
CC -!- COFACTOR:
CC Name=Mn(2+); Xref=ChEBI:CHEBI:29035;
CC Evidence={ECO:0000269|PubMed:21451980};
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000269|PubMed:21451980};
CC Note=Has an absolute requirement of bivalent metal ions Mg(2+) or
CC Mn(2+). {ECO:0000269|PubMed:21451980};
CC -!- ACTIVITY REGULATION: Is inhibited by Li(+) and by inorganic phosphate.
CC {ECO:0000269|PubMed:15470127, ECO:0000269|PubMed:21451980}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=15 uM for D-fructose 1,6-bisphosphate
CC {ECO:0000269|PubMed:15470127};
CC KM=44 uM for D-fructose 1,6-bisphosphate
CC {ECO:0000269|PubMed:21451980};
CC Vmax=1.6 umol/min/mg enzyme {ECO:0000269|PubMed:21451980};
CC Note=kcat is 1.0 sec(-1). {ECO:0000269|PubMed:21451980};
CC pH dependence:
CC Optimum pH is 9.0. Is active over a pH range from 7 to 9.
CC {ECO:0000269|PubMed:21451980};
CC Temperature dependence:
CC Retains its full activity until 30 degrees Celsius. A significant
CC loss in the activity (65% loss) is noted at 40 degrees Celsius.
CC Complete inactivation of the enzyme occurs at temperatures greater
CC than 50 degrees Celsius. {ECO:0000269|PubMed:21451980};
CC -!- PATHWAY: Carbohydrate biosynthesis; gluconeogenesis.
CC {ECO:0000305|PubMed:26258286}.
CC -!- SUBUNIT: Homooligomer (PubMed:21451980). Probably a dimer
CC (PubMed:21636919). {ECO:0000269|PubMed:21451980,
CC ECO:0000269|PubMed:21636919}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250}.
CC -!- INDUCTION: Is expressed during exponential growth, with mRNA levels
CC approximately half of the level of sigA. {ECO:0000269|PubMed:15470127}.
CC -!- DISRUPTION PHENOTYPE: Cells lacking this gene are shown to be highly
CC attenuated in a mouse tuberculosis model (PubMed:14569030). However,
CC another study shows that in a mouse model of M.tuberculosis infection,
CC cells lacking this gene are able to replicate and persist in lungs
CC similar to the wild-type strain (PubMed:26258286). The mutant cells
CC grow on gluconeogenic carbon sources and have detectable FBPase
CC activity, due to the alternative FBPase (Gpm2, Rv3214)
CC (PubMed:26258286). A third study shows that disruption of glpX leads to
CC a growth profile comparable to that of wild-type when grown on the
CC standard enrichment media, but growth is dysgonic with individual
CC gluconeogenic substrates such as oleic acid, glycerol and acetate, and
CC the mutant strain fails to efficiently replicate during the acute phase
CC (i.e. first 30 days post-infection) of infection and begins to die
CC thereafter (PubMed:26397812). Cells lacking both glpX and gpm2 grow as
CC well as wild-type on glucose, but are unable to grow on any of the
CC gluconeogenic carbon sources tested (glycerol, acetate and butyrate);
CC the growth defect on gluconeogenic carbon sources is fully complemented
CC by restoring expression of either GlpX or Gpm2. This double mutant
CC lacks detectable FBPase activity and accumulates FBP. It is also
CC severely attenuated in a mouse model of infection, as it fails to
CC replicate in mouse lungs during the first 10 days of infection and
CC begins to die thereafter (PubMed:26258286).
CC {ECO:0000269|PubMed:14569030, ECO:0000269|PubMed:26258286,
CC ECO:0000269|PubMed:26397812}.
CC -!- MISCELLANEOUS: Gluconeogenesis is critical to M.tuberculosis ability to
CC establish infection and is necessary for its survival in the host.
CC {ECO:0000269|PubMed:26258286}.
CC -!- SIMILARITY: Belongs to the FBPase class 2 family. {ECO:0000305}.
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DR EMBL; AL123456; CCP43852.1; -; Genomic_DNA.
DR PIR; A70897; A70897.
DR RefSeq; NP_215615.3; NC_000962.3.
DR RefSeq; WP_003898726.1; NZ_NVQJ01000021.1.
DR AlphaFoldDB; P9WN21; -.
DR SMR; P9WN21; -.
DR STRING; 83332.Rv1099c; -.
DR iPTMnet; P9WN21; -.
DR PaxDb; P9WN21; -.
DR PRIDE; P9WN21; -.
DR DNASU; 885861; -.
DR GeneID; 45425073; -.
DR GeneID; 885861; -.
DR KEGG; mtu:Rv1099c; -.
DR PATRIC; fig|83332.111.peg.1226; -.
DR TubercuList; Rv1099c; -.
DR eggNOG; COG1494; Bacteria.
DR BRENDA; 3.1.3.11; 3445.
DR UniPathway; UPA00138; -.
DR PHI-base; PHI:6486; -.
DR PHI-base; PHI:6487; -.
DR Proteomes; UP000001584; Chromosome.
DR GO; GO:0005829; C:cytosol; HDA:MTBBASE.
DR GO; GO:0042132; F:fructose 1,6-bisphosphate 1-phosphatase activity; IDA:MTBBASE.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0030388; P:fructose 1,6-bisphosphate metabolic process; IBA:GO_Central.
DR GO; GO:0006094; P:gluconeogenesis; IMP:MTBBASE.
DR GO; GO:0006071; P:glycerol metabolic process; IEA:InterPro.
DR CDD; cd01516; FBPase_glpX; 1.
DR InterPro; IPR004464; FBPase_class-2/SBPase.
DR PANTHER; PTHR30447; PTHR30447; 1.
DR Pfam; PF03320; FBPase_glpX; 1.
DR PIRSF; PIRSF004532; GlpX; 1.
DR TIGRFAMs; TIGR00330; glpX; 1.
PE 1: Evidence at protein level;
KW Acetylation; Carbohydrate metabolism; Cytoplasm; Direct protein sequencing;
KW Gluconeogenesis; Hydrolase; Manganese; Metal-binding; Reference proteome.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000269|PubMed:17259624,
FT ECO:0000269|PubMed:34915127"
FT CHAIN 2..362
FT /note="Fructose-1,6-bisphosphatase class 2"
FT /id="PRO_0000403673"
FT REGION 1..32
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1..17
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 61
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P0A9C9"
FT BINDING 85
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P0A9C9"
FT BINDING 113
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P0A9C9"
FT BINDING 116..118
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:P0A9C9"
FT BINDING 116
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P0A9C9"
FT BINDING 148
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:P0A9C9"
FT BINDING 193..195
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:P0A9C9"
FT BINDING 215..217
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:P0A9C9"
FT BINDING 239
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:P0A9C9"
FT BINDING 242
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P0A9C9"
FT MOD_RES 2
FT /note="N-acetylthreonine; partial"
FT /evidence="ECO:0000269|PubMed:17259624"
SQ SEQUENCE 362 AA; 38084 MW; 113D5BA2742F06E9 CRC64;
MTAEGSGSST AAVASHDPSH TRPSRREAPD RNLAMELVRV TEAGAMAAGR WVGRGDKEGG
DGAAVDAMRE LVNSVSMRGV VVIGEGEKDH APMLYNGEEV GNGDGPECDF AVDPIDGTTL
MSKGMTNAIS VLAVADRGTM FDPSAVFYMN KIAVGPDAAH VLDITAPISE NIRAVAKVKD
LSVRDMTVCI LDRPRHAQLI HDVRATGARI RLITDGDVAG AISACRPHSG TDLLAGIGGT
PEGIIAAAAI RCMGGAIQAQ LAPRDDAERR KALEAGYDLN QVLTTEDLVS GENVFFCATG
VTDGDLLKGV RYYPGGCTTH SIVMRSKSGT VRMIEAYHRL SKLNEYSAID FTGDSSAVYP
LP
