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4  structures 72  species 0  interactions 75  sequences 1  architecture

Family: Pfk_N (PF18468)

Summary: Phosphofructokinase N-terminal domain yeast

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Phosphofructokinase Edit Wikipedia article

Phosphofructokinase
Identifiers
Symbol Ppfruckinase
Pfam PF00365
InterPro IPR000023
PROSITE PDOC00336

Phosphofructokinase is a kinase enzyme that phosphorylates fructose 6-phosphate in glycolysis.

Function

The enzyme-catalysed transfer of a phosphoryl group from ATP is an important reaction in a wide variety of biological processes.[1] One enzyme that utilizes this reaction is phosphofructokinase (PFK), which catalyses the phosphorylation of fructose-6-phosphate to fructose-1,6- bisphosphate, a key regulatory step in the glycolytic pathway.[2][3] It is allosterically inhibited by ATP and allosterically activated by AMP, thus indicating the cell's energetic needs when it undergoes the glycolytic pathway.[4] PFK exists as a homotetramer in bacteria and mammals (where each monomer possesses 2 similar domains) and as an octomer in yeast (where there are 4 alpha- (PFK1) and 4 beta-chains (PFK2), the latter, like the mammalian monomers, possessing 2 similar domains[3]). This protein may use the morpheein model of allosteric regulation.[5]

PFK is about 300 amino acids in length, and structural studies of the bacterial enzyme have shown it comprises two similar (alpha/beta) lobes: one involved in ATP binding and the other housing both the substrate-binding site and the allosteric site (a regulatory binding site distinct from the active site, but that affects enzyme activity). The identical tetramer subunits adopt 2 different conformations: in a 'closed' state, the bound magnesium ion bridges the phosphoryl groups of the enzyme products (ADP and fructose-1,6- bisphosphate); and in an 'open' state, the magnesium ion binds only the ADP,[6] as the 2 products are now further apart. These conformations are thought to be successive stages of a reaction pathway that requires subunit closure to bring the 2 molecules sufficiently close to react.[6]

PFK belongs to the phosphofructokinase B (PfkB) family of sugar kinases [7]. Other members of this family (also known as the Ribokinase family) include ribokinase (RK) adenosine kinase (AK), inosine kinase, and 1-phosphofructokinase.[7][8][9] The members of the PfkB/RK family are identified by the presence of three conserved sequence motifs.[7][8][10] The structures of several PfK family of proteins have been determined from a number of organisms and the enzymatic activity of this family of protein shows a dependence on the presence of pentavalent ions.[11] [7][10]

Deficiency in PFK leads to glycogenosis type VII (Tarui's disease), an autosomal recessive disorder characterised by severe nausea, vomiting, muscle cramps and myoglobinuria in response to bursts of intense or vigorous exercise.[3] Sufferers are usually able to lead a reasonably ordinary life by learning to adjust activity levels.[3]

The reverse reaction is catalyzed by the enzyme Fructose-1,6-bisphosphatase.

Regulation

There are two different phosphofructokinase enzymes in humans:

Type Synonyms EC number Substrate Product Subunit genes
Phosphofructokinase 1 6-phosphofructokinase
phosphohexokinase
EC 2.7.1.11 Beta-D-fructose-6-phosphate wpmp.png
Fructose 6-phosphate
Beta-D-fructose-1,6-bisphosphate wpmp.png
Fructose-1,6-bisphosphate
PFKL, PFKM, PFKP
Phosphofructokinase 2 6-phosphofructo-2-kinase EC 2.7.1.105 Fructose 2,6-bisphosphate.svg
Fructose-2,6-bisphosphate
PFKFB1, PFKFB2, PFKFB3, PFKFB4

See also

References

  1. ^ Evans PR, Hellinga HW (1987). "Mutations in the active site of Escherichia coli phosphofructokinase". Nature. 327 (6121): 437–439. doi:10.1038/327437a0. PMID 2953977. 
  2. ^ Wegener G, Krause U (2002). "Different modes of activating phosphofructokinase, a key regulatory enzyme of glycolysis, in working vertebrate muscle". Biochem. Soc. Trans. 30 (2): 264–270. doi:10.1042/bst0300264. PMID 12023862. 
  3. ^ a b c d Raben N, Exelbert R, Spiegel R, Sherman JB, Nakajima H, Plotz P, Heinisch J (1995). "Functional expression of human mutant phosphofructokinase in yeast: genetic defects in French Canadian and Swiss patients with phosphofructokinase deficiency". Am. J. Hum. Genet. 56 (1): 131–141. PMC 1801305Freely accessible. PMID 7825568. 
  4. ^ Garrett, Reginald; Grisham, Reginald (2012). Biochemistry. Cengage Learning. p. 585. ISBN 978-1133106296. 
  5. ^ T. Selwood; E. K. Jaffe. (2011). "Dynamic dissociating homo-oligomers and the control of protein function". Arch. Biochem. Biophys. 519 (2): 131–43. doi:10.1016/j.abb.2011.11.020. PMC 3298769Freely accessible. PMID 22182754. 
  6. ^ a b Shirakihara Y, Evans PR (1988). "Crystal structure of the complex of phosphofructokinase from Escherichia coli with its reaction products". J. Mol. Biol. 204 (4): 973–994. doi:10.1016/0022-2836(88)90056-3. PMID 2975709. 
  7. ^ a b c d Park J, Gupta RS: Adenosine kinase and ribokinase--the RK family of proteins. Cell Mol Life Sci 2008, 65: 2875-2896.
  8. ^ a b Bork P, Sander C, Valencia A: Convergent evolution of similar enzymatic function on different protein folds: the hexokinase, ribokinase, and galactokinase families of sugar kinases. Protein Sci 1993, 2: 31-40.
  9. ^ Spychala J, Datta NS, Takabayashi K, Datta M, Fox IH, Gribbin T, Mitchell BS: Cloning of human adenosine kinase cDNA: sequence similarity to microbial ribokinases and fructokinases. Proc Natl Acad Sci U S A 1996, 93: 1232-1237.
  10. ^ a b Maj MC, Singh B, Gupta RS: Pentavalent ions dependency is a conserved property of adenosine kinase from diverse sources: identification of a novel motif implicated in phosphate and magnesium ion binding and substrate inhibition. Biochemistry 2002, 41: 4059-4069.
  11. ^ Sigrell JA, Cameron AD, Jones TA, Mowbray SL: Structure of Escherichia coli ribokinase in complex with ribose and dinucleotide determined to 1.8 A resolution: insights into a new family of kinase structures. Structure 1998, 6: 183-193.

External links

This article incorporates text from the public domain Pfam and InterPro IPR000023


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This tab holds the annotation information that is stored in the Pfam database. As we move to using Wikipedia as our main source of annotation, the contents of this tab will be gradually replaced by the Wikipedia tab.

Phosphofructokinase N-terminal domain yeast Provide feedback

This is a phosphofructokinase (Pfk) N-terminal domain found in yeast ATP-dependent 6-phosphofructokinase subunit alpha. ATP-dependent 6-phosphofructokinases (Pfks, EC 2.7.1.11) catalyze the phosphorylation of fructose 6-phosphate (F-6-P) to fructose 1,6-bisphosphate, a key control step of glycolysis in most organisms. The N-terminal domain contains the active site and is related to glyoxalase I (E.C. 4.4.1.5) [1].

Literature references

  1. Strater N, Marek S, Kuettner EB, Kloos M, Keim A, Bruser A, Kirchberger J, Schoneberg T;, FASEB J. 2011;25:89-98.: Molecular architecture and structural basis of allosteric regulation of eukaryotic phosphofructokinases. PUBMED:20833871 EPMC:20833871


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Domain organisation

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Pfam Clan

This family is a member of clan PFK (CL0240), which has the following description:

This clan includes two SCOP superfamilies. Strong similarities between NAD kinases, DAG kinase, sphingosine kinase and PFK have previously been shown[1].

The clan contains the following 4 members:

DAGK_cat NAD_kinase PFK Pfk_N

Alignments

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RP35
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RP55
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RP75
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(9)
Full
(75)
Representative proteomes UniProt
(117)
NCBI
(136)
Meta
(0)
RP15
(22)
RP35
(47)
RP55
(63)
RP75
(72)
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Curation and family details

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This family is new in this Pfam release.

Seed source: ECOD:EUF02430
Previous IDs: none
Type: Domain
Sequence Ontology: SO:0000417
Author: El-Gebali S
Number in seed: 9
Number in full: 75
Average length of the domain: 94.30 aa
Average identity of full alignment: 39 %
Average coverage of the sequence by the domain: 9.61 %

HMM information View help on HMM parameters

HMM build commands:
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 45638612 -E 1000 --cpu 4 HMM pfamseq
Model details:
Parameter Sequence Domain
Gathering cut-off 26.8 26.8
Trusted cut-off 27.4 28.0
Noise cut-off 25.6 26.2
Model length: 98
Family (HMM) version: 1
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Structures

For those sequences which have a structure in the Protein DataBank, we use the mapping between UniProt, PDB and Pfam coordinate systems from the PDBe group, to allow us to map Pfam domains onto UniProt sequences and three-dimensional protein structures. The table below shows the structures on which the Pfk_N domain has been found. There are 4 instances of this domain found in the PDB. Note that there may be multiple copies of the domain in a single PDB structure, since many structures contain multiple copies of the same protein sequence.

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