P9WID3 · PFKB_MYCTU
- ProteinATP-dependent 6-phosphofructokinase isozyme 2
- GenepfkB
- StatusUniProtKB reviewed (Swiss-Prot)
- Amino acids339 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
Catalyzes the phosphorylation of D-fructose 6-phosphate to fructose 1,6-bisphosphate by ATP, the first committing step of glycolysis (PubMed:33540748).
Can also catalyze the phosphorylation of tagatose-6-phosphate. The catalytic efficiency with tagatose-6-phosphate is about 1.8 times lower than that with fructose 6-phosphate (PubMed:33540748).
Can use phosphate donors other than ATP (GTP and ITP), with lower efficiency (PubMed:33540748).
In addition, can catalyze the reverse gluconeogenic reaction, albeit with low efficiency (PubMed:33540748).
May support and maintain basic glycolysis and metabolic fluxes during conditions inhibiting PfkA (PubMed:33540748).
Can also catalyze the phosphorylation of tagatose-6-phosphate. The catalytic efficiency with tagatose-6-phosphate is about 1.8 times lower than that with fructose 6-phosphate (PubMed:33540748).
Can use phosphate donors other than ATP (GTP and ITP), with lower efficiency (PubMed:33540748).
In addition, can catalyze the reverse gluconeogenic reaction, albeit with low efficiency (PubMed:33540748).
May support and maintain basic glycolysis and metabolic fluxes during conditions inhibiting PfkA (PubMed:33540748).
Miscellaneous
Activity of PfkB is tenfold lower than that of PfkA (PubMed:33540748).
Activity with tagatose-6-phosphate suggests that PfkA and/or PfkB may substitute for tagatose-6-phosphate kinase and further support glycolysis (PubMed:33540748).
Activity with tagatose-6-phosphate suggests that PfkA and/or PfkB may substitute for tagatose-6-phosphate kinase and further support glycolysis (PubMed:33540748).
Was identified as a high-confidence drug target.
Catalytic activity
- ATP + beta-D-fructose 6-phosphate = ADP + beta-D-fructose 1,6-bisphosphate + H+This reaction proceeds in the forward and the backward directions.
Cofactor
Note: The magnesium does not function as an allosteric effector but is essential for glycolytic reaction.
Activity regulation
Not inhibited by an excess of substrates and common allosteric inhibitors. Inhibited by high concentrations of the reaction products, fructose 1,6-bisphosphate and ADP.
Biotechnology
Has strong T-cell and IFN-gamma inducing capacity in human tuberculin skin test positive patients, indicating this might be a good vaccine candidate.
Kinetics
KM | SUBSTRATE | pH | TEMPERATURE[C] | NOTES | EVIDENCE | |
---|---|---|---|---|---|---|
0.04 mM | fructose 6-phosphate | |||||
0.052 mM | ATP | |||||
0.09 mM | tagatose-6-phosphate | |||||
17.5 mM | fructose 1,6-bisphosphate (for gluconeogenic reaction) | |||||
12.9 mM | ADP (for gluconeogenic reaction) | |||||
0.27 mM | IDP (for gluconeogenic reaction) | |||||
0.28 mM | GDP (for gluconeogenic reaction) |
Vmax | pH | TEMPERATURE[C] | NOTES | EVIDENCE | |
---|---|---|---|---|---|
1.2 μmol/min/mg | with fructose 6-phosphate as substrate | ||||
0.8 μmol/min/mg | with ATP as substrate | ||||
1.5 μmol/min/mg | with tagatose-6-phosphate as substrate | ||||
0.39 μmol/min/mg | with fructose 1,6-bisphosphate as substrate (for gluconeogenic reaction) | ||||
3.6 μmol/min/mg | with ADP as substrate (for gluconeogenic reaction) | ||||
0.37 μmol/min/mg | with IDP as substrate (for gluconeogenic reaction) | ||||
0.32 μmol/min/mg | with GDP as substrate (for gluconeogenic reaction) |
Pathway
Carbohydrate degradation; glycolysis; D-glyceraldehyde 3-phosphate and glycerone phosphate from D-glucose: step 3/4.
Features
Showing features for binding site, active site.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Binding site | 22-24 | substrate | ||||
Sequence: ALD | ||||||
Binding site | 37 | ATP (UniProtKB | ChEBI); ligand shared between dimeric partners | ||||
Sequence: K | ||||||
Binding site | 37-39 | substrate | ||||
Sequence: KMR | ||||||
Binding site | 49-53 | substrate | ||||
Sequence: GGGIN | ||||||
Binding site | 100-102 | substrate | ||||
Sequence: RES | ||||||
Binding site | 150 | substrate | ||||
Sequence: S | ||||||
Binding site | 194-196 | ATP (UniProtKB | ChEBI); ligand shared between dimeric partners; in other chain | ||||
Sequence: KAS | ||||||
Binding site | 199 | Mg2+ (UniProtKB | ChEBI); catalytic | ||||
Sequence: E | ||||||
Binding site | 233-238 | ATP (UniProtKB | ChEBI); ligand shared between dimeric partners; in other chain | ||||
Sequence: SLGSQG | ||||||
Binding site | 259 | K+ (UniProtKB | ChEBI) | ||||
Sequence: S | ||||||
Binding site | 261 | K+ (UniProtKB | ChEBI) | ||||
Sequence: V | ||||||
Active site | 265 | |||||
Sequence: D | ||||||
Binding site | 265 | substrate | ||||
Sequence: D | ||||||
Binding site | 295 | K+ (UniProtKB | ChEBI) | ||||
Sequence: M | ||||||
Binding site | 298 | K+ (UniProtKB | ChEBI) | ||||
Sequence: T | ||||||
Binding site | 300 | K+ (UniProtKB | ChEBI) | ||||
Sequence: G | ||||||
Binding site | 302 | K+ (UniProtKB | ChEBI) | ||||
Sequence: A |
GO annotations
Aspect | Term | |
---|---|---|
Cellular Component | cytosol | |
Molecular Function | 6-phosphofructokinase activity | |
Molecular Function | ATP binding | |
Molecular Function | metal ion binding | |
Molecular Function | tagatose-6-phosphate kinase activity |
Keywords
- Molecular function
- Biological process
- Ligand
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended nameATP-dependent 6-phosphofructokinase isozyme 2
- EC number
- Short namesATP-PFK 2; Phosphofructokinase 2
- Alternative names
Gene names
Organism names
- Strain
- Taxonomic lineageBacteria > Actinomycetota > Actinomycetes > Mycobacteriales > Mycobacteriaceae > Mycobacterium > Mycobacterium tuberculosis complex
Accessions
- Primary accessionP9WID3
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
UniProt Annotation
GO Annotation
Phenotypes & Variants
PTM/Processing
Features
Showing features for initiator methionine, modified residue, chain, cross-link.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Initiator methionine | 1 | Removed | ||||
Sequence: M | ||||||
Modified residue | 2 | N-acetylthreonine | ||||
Sequence: T | ||||||
Chain | PRO_0000392912 | 2-339 | ATP-dependent 6-phosphofructokinase isozyme 2 | |||
Sequence: TEPAAWDEGKPRIITLTMNPALDITTSVDVVRPTEKMRCGAPRYDPGGGGINVARIVHVLGGCSTALFPAGGSTGSLLMALLGDAGVPFRVIPIAASTRESFTVNESRTAKQYRFVLPGPSLTVAEQEQCLDELRGAAASAAFVVASGSLPPGVAADYYQRVADICRRSSTPLILDTSGGGLQHISSGVFLLKASVRELRECVGSELLTEPEQLAAAHELIDRGRAEVVVVSLGSQGALLATRHASHRFSSIPMTAVSGVGAGDAMVAAITVGLSRGWSLIKSVRLGNAAGAAMLLTPGTAACNRDDVERFFELAAEPTEVGQDQYVWHPIVNPEASP | ||||||
Cross-link | 283 | Isoglutamyl lysine isopeptide (Lys-Gln) (interchain with Q-Cter in protein Pup) | ||||
Sequence: K |
Keywords
- PTM
Proteomic databases
PTM databases
Expression
Induction
A member of the dormancy regulon. Induced in response to reduced oxygen tension (hypoxia), low levels of nitric oxide (NO) and carbon monoxide (CO). It is hoped that this regulon will give insight into the latent, or dormant phase of infection.
Interaction
Protein-protein interaction databases
Structure
Sequence
- Sequence statusComplete
- Length339
- Mass (Da)35,401
- Last updated2014-04-16 v1
- ChecksumD773E363FF73DADD
Keywords
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
AL123456 EMBL· GenBank· DDBJ | CCP44802.1 EMBL· GenBank· DDBJ | Genomic DNA |