4RH3
AMPPCP-bound structure of human platelet phosphofructokinase in an R-state, crystal form II
Summary for 4RH3
| Entry DOI | 10.2210/pdb4rh3/pdb |
| Related | 3OPY 4OMT 4U1R 4WLO 4XZ2 |
| Descriptor | ATP-dependent 6-phosphofructokinase, platelet type, PHOSPHOMETHYLPHOSPHONIC ACID ADENYLATE ESTER, PHOSPHATE ION (3 entities in total) |
| Functional Keywords | phosphohexokinase, transferase |
| Biological source | Homo sapiens (human) |
| Cellular location | Cytoplasm : Q01813 |
| Total number of polymer chains | 4 |
| Total formula weight | 327133.01 |
| Authors | Kloos, M. (deposition date: 2014-10-01, release date: 2015-06-24, Last modification date: 2024-02-28) |
| Primary citation | Kloos, M.,Bruser, A.,Kirchberger, J.,Schoneberg, T.,Strater, N. Crystal structure of human platelet phosphofructokinase-1 locked in an activated conformation. Biochem.J., 469:421-432, 2015 Cited by PubMed Abstract: Phosphofructokinase-1 (Pfk) acts as the main control point of flux through glycolysis. It is involved in complex allosteric regulation and Pfk mutations have been linked to cancer development. Whereas the 3D structure and structural basis of allosteric regulation of prokaryotic Pfk has been studied in great detail, our knowledge about the molecular basis of the allosteric behaviour of the more complex mammalian Pfk is still very limited. To characterize the structural basis of allosteric regulation, the subunit interfaces and the functional consequences of modifications in Tarui's disease and cancer, we analysed the physiological homotetramer of human platelet Pfk at up to 2.67 Å resolution in two crystal forms. The crystallized enzyme is permanently activated by a deletion of the 22 C-terminal residues. Complex structures with ADP and fructose-6-phosphate (F6P) and with ATP suggest a role of three aspartates in the deprotonation of the OH-nucleophile of F6P and in the co-ordination of the catalytic magnesium ion. Changes at the dimer interface, including an asymmetry observed in both crystal forms, are the primary mechanism of allosteric regulation of Pfk by influencing the F6P-binding site. Whereas the nature of this conformational switch appears to be largely conserved in bacterial, yeast and mammalian Pfk, initiation of these changes differs significantly in eukaryotic Pfk. PubMed: 26205495DOI: 10.1042/BJ20150251 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (3.02 Å) |
Structure validation
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