PFKA_MYCTU
ID PFKA_MYCTU Reviewed; 343 AA.
AC P9WID7; L0TBI5; O53257; P65690;
DT 16-APR-2014, integrated into UniProtKB/Swiss-Prot.
DT 16-APR-2014, sequence version 1.
DT 03-AUG-2022, entry version 44.
DE RecName: Full=ATP-dependent 6-phosphofructokinase {ECO:0000255|HAMAP-Rule:MF_01976};
DE Short=ATP-PFK {ECO:0000255|HAMAP-Rule:MF_01976};
DE Short=Phosphofructokinase {ECO:0000255|HAMAP-Rule:MF_01976};
DE EC=2.7.1.11 {ECO:0000255|HAMAP-Rule:MF_01976, ECO:0000269|PubMed:33540748};
DE AltName: Full=Phosphofructokinase A {ECO:0000303|PubMed:33540748};
DE AltName: Full=Phosphohexokinase {ECO:0000255|HAMAP-Rule:MF_01976};
DE AltName: Full=Tagatose-6-phosphate kinase {ECO:0000305};
DE EC=2.7.1.144 {ECO:0000269|PubMed:33540748};
GN Name=pfkA {ECO:0000255|HAMAP-Rule:MF_01976, ECO:0000303|PubMed:33540748};
GN OrderedLocusNames=Rv3010c; ORFNames=MTV012.24c;
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 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 [3]
RP FUNCTION, CATALYTIC ACTIVITY, COFACTOR, ACTIVITY REGULATION,
RP BIOPHYSICOCHEMICAL PROPERTIES, AND PATHWAY.
RX PubMed=33540748; DOI=10.3390/ijms22031483;
RA Snasel J., Machova I., Solinova V., Kasicka V., Krecmerova M., Pichova I.;
RT "Phosphofructokinases A and B from Mycobacterium tuberculosis display
RT different catalytic properties and allosteric regulation.";
RL Int. J. Mol. Sci. 22:0-0(2021).
CC -!- FUNCTION: Catalyzes the phosphorylation of D-fructose 6-phosphate to
CC fructose 1,6-bisphosphate by ATP, the first committing step of
CC glycolysis (PubMed:33540748). Can also catalyze the phosphorylation of
CC tagatose-6-phosphate. Both sugar phosphates can function equivalently
CC as substrates (PubMed:33540748). Cannot catalyze the reverse
CC gluconeogenic reaction (PubMed:33540748).
CC {ECO:0000269|PubMed:33540748}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + beta-D-fructose 6-phosphate = ADP + beta-D-fructose 1,6-
CC bisphosphate + H(+); Xref=Rhea:RHEA:16109, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:30616, ChEBI:CHEBI:32966, ChEBI:CHEBI:57634,
CC ChEBI:CHEBI:456216; EC=2.7.1.11; Evidence={ECO:0000255|HAMAP-
CC Rule:MF_01976, ECO:0000269|PubMed:33540748};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:16110;
CC Evidence={ECO:0000269|PubMed:33540748};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + D-tagatofuranose 6-phosphate = ADP + D-tagatofuranose
CC 1,6-bisphosphate + H(+); Xref=Rhea:RHEA:12420, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:30616, ChEBI:CHEBI:58694, ChEBI:CHEBI:58695,
CC ChEBI:CHEBI:456216; EC=2.7.1.144;
CC Evidence={ECO:0000269|PubMed:33540748};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000255|HAMAP-Rule:MF_01976,
CC ECO:0000269|PubMed:33540748};
CC Note=Magnesium may play a role in formation and maintaining of proper
CC enzyme conformation and multimerization. {ECO:0000269|PubMed:33540748};
CC -!- ACTIVITY REGULATION: Inhibited by high concentrations of the substrates
CC fructose 6-phosphate and ATP, and by the reaction products, fructose
CC 1,6-bisphosphate and ADP. Allosterically inhibited by
CC phosphoenolpyruvate (PEP), guanosine diphosphate (GDP) and citrate.
CC {ECO:0000269|PubMed:33540748}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=0.4 mM for fructose 6-phosphate {ECO:0000269|PubMed:33540748};
CC KM=1.0 mM for ATP {ECO:0000269|PubMed:33540748};
CC KM=0.43 mM for tagatose-6-phosphate {ECO:0000269|PubMed:33540748};
CC Vmax=20 umol/min/mg enzyme with fructose 6-phosphate as substrate
CC {ECO:0000269|PubMed:33540748};
CC Vmax=19 umol/min/mg enzyme with ATP as substrate
CC {ECO:0000269|PubMed:33540748};
CC Vmax=30 umol/min/mg enzyme with tagatose-6-phosphate as substrate
CC {ECO:0000269|PubMed:33540748};
CC -!- PATHWAY: Carbohydrate degradation; glycolysis; D-glyceraldehyde 3-
CC phosphate and glycerone phosphate from D-glucose: step 3/4.
CC {ECO:0000255|HAMAP-Rule:MF_01976, ECO:0000305|PubMed:33540748}.
CC -!- SUBUNIT: Homodimer or homotetramer. {ECO:0000255|HAMAP-Rule:MF_01976}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000255|HAMAP-Rule:MF_01976}.
CC -!- MISCELLANEOUS: Activity of PfkA is tenfold higher than that of PfkB
CC (PubMed:33540748). Activity with tagatose-6-phosphate suggests that
CC PfkA and/or PfkB may substitute for tagatose-6-phosphate kinase and
CC further support glycolysis (PubMed:33540748).
CC {ECO:0000269|PubMed:33540748}.
CC -!- SIMILARITY: Belongs to the phosphofructokinase type A (PFKA) family.
CC Mixed-substrate PFK group III subfamily. {ECO:0000255|HAMAP-
CC Rule:MF_01976}.
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DR EMBL; AL123456; CCP45816.1; -; Genomic_DNA.
DR PIR; E70856; E70856.
DR RefSeq; NP_217526.1; NC_000962.3.
DR RefSeq; WP_003415251.1; NZ_NVQJ01000041.1.
DR AlphaFoldDB; P9WID7; -.
DR SMR; P9WID7; -.
DR STRING; 83332.Rv3010c; -.
DR PaxDb; P9WID7; -.
DR DNASU; 888509; -.
DR GeneID; 888509; -.
DR KEGG; mtu:Rv3010c; -.
DR TubercuList; Rv3010c; -.
DR eggNOG; COG0205; Bacteria.
DR OMA; KFAVICV; -.
DR PhylomeDB; P9WID7; -.
DR UniPathway; UPA00109; UER00182.
DR Proteomes; UP000001584; Chromosome.
DR GO; GO:0005945; C:6-phosphofructokinase complex; IBA:GO_Central.
DR GO; GO:0009274; C:peptidoglycan-based cell wall; HDA:MTBBASE.
DR GO; GO:0005886; C:plasma membrane; HDA:MTBBASE.
DR GO; GO:0003872; F:6-phosphofructokinase activity; IBA:GO_Central.
DR GO; GO:0016208; F:AMP binding; IBA:GO_Central.
DR GO; GO:0005524; F:ATP binding; IBA:GO_Central.
DR GO; GO:0047334; F:diphosphate-fructose-6-phosphate 1-phosphotransferase activity; IEA:InterPro.
DR GO; GO:0070095; F:fructose-6-phosphate binding; IBA:GO_Central.
DR GO; GO:0042802; F:identical protein binding; IBA:GO_Central.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0048029; F:monosaccharide binding; IBA:GO_Central.
DR GO; GO:0009024; F:tagatose-6-phosphate kinase activity; IEA:RHEA.
DR GO; GO:0061621; P:canonical glycolysis; IBA:GO_Central.
DR GO; GO:0030388; P:fructose 1,6-bisphosphate metabolic process; IBA:GO_Central.
DR GO; GO:0006002; P:fructose 6-phosphate metabolic process; IBA:GO_Central.
DR Gene3D; 3.40.50.460; -; 1.
DR HAMAP; MF_01976; Phosphofructokinase_III; 1.
DR InterPro; IPR022953; ATP_PFK.
DR InterPro; IPR012003; ATP_PFK_prok-type.
DR InterPro; IPR015912; Phosphofructokinase_CS.
DR InterPro; IPR000023; Phosphofructokinase_dom.
DR InterPro; IPR012829; Phosphofructokinase_III.
DR InterPro; IPR035966; PKF_sf.
DR Pfam; PF00365; PFK; 1.
DR PIRSF; PIRSF000532; ATP_PFK_prok; 1.
DR PRINTS; PR00476; PHFRCTKINASE.
DR SUPFAM; SSF53784; SSF53784; 1.
DR TIGRFAMs; TIGR02483; PFK_mixed; 1.
DR PROSITE; PS00433; PHOSPHOFRUCTOKINASE; 1.
PE 1: Evidence at protein level;
KW Allosteric enzyme; ATP-binding; Cytoplasm; Glycolysis; Kinase; Magnesium;
KW Metal-binding; Nucleotide-binding; Reference proteome; Transferase.
FT CHAIN 1..343
FT /note="ATP-dependent 6-phosphofructokinase"
FT /id="PRO_0000111968"
FT ACT_SITE 128
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01976"
FT BINDING 10
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01976"
FT BINDING 73..74
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01976"
FT BINDING 103..106
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01976"
FT BINDING 104
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01976"
FT BINDING 126..128
FT /ligand="substrate"
FT /ligand_note="ligand shared between dimeric partners"
FT /note="in other chain"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01976"
FT BINDING 163
FT /ligand="substrate"
FT /ligand_note="ligand shared between dimeric partners"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01976"
FT BINDING 170..172
FT /ligand="substrate"
FT /ligand_note="ligand shared between dimeric partners"
FT /note="in other chain"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01976"
FT BINDING 223
FT /ligand="substrate"
FT /ligand_note="ligand shared between dimeric partners"
FT /note="in other chain"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01976"
FT BINDING 267
FT /ligand="substrate"
FT /ligand_note="ligand shared between dimeric partners"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01976"
FT BINDING 273..276
FT /ligand="substrate"
FT /ligand_note="ligand shared between dimeric partners"
FT /note="in other chain"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01976"
FT SITE 105
FT /note="Important for substrate specificity; cannot use PPi
FT as phosphoryl donor"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01976"
SQ SEQUENCE 343 AA; 36880 MW; 826E5FF16A6ECABA CRC64;
MRIGVLTGGG DCPGLNAVIR AVVRTCHARY GSSVVGFQNG FRGLLENRRV QLHNDDRNDR
LLAKGGTMLG TARVHPDKLR AGLPQIMQTL DDNGIDVLIP IGGEGTLTAA SWLSEENVPV
VGVPKTIDND IDCTDVTFGH DTALTVATEA IDRLHSTAES HERVMLVEVM GRHAGWIALN
AGLASGAHMT LIPEQPFDIE EVCRLVKGRF QRGDSHFICV VAEGAKPAPG TIMLREGGLD
EFGHERFTGV AAQLAVEVEK RINKDVRVTV LGHIQRGGTP TAYDRVLATR FGVNAADAAH
AGEYGQMVTL RGQDIGRVPL ADAVRKLKLV PQSRYDDAAA FFG
