5mwl | pdb_00005mwl
INOSITOL 1,3,4,5,6-PENTAKISPHOSPHATE 2-KINASE FROM M. MUSCULUS IN COMPLEX WITH ATP and IP5
Structural highlights
Function[IPPK_MOUSE] Phosphorylates Ins(1,3,4,5,6)P5 at position 2 to form Ins(1,2,3,4,5,6)P6 (InsP6 or phytate). InsP6 is involved in many processes such as mRNA export, non-homologous end-joining, endocytosis, ion channel regulation. It also protects cells from TNF-alpha-induced apoptosis.[1] Publication Abstract from PubMedInositol 1,3,4,5,6-pentakisphosphate 2-kinases (IP5 2-Ks) comprise a family of enzymes in charge of synthesizing inositol hexakisphosphate (IP6) in eukaryotic cells. This protein and its product IP6 present many roles in cells, participating in mRNA export, embryonic development, and apoptosis. We reported previously that the full-length IP5 2-K from Arabidopsis thaliana (At) is a zinc metallo-enzyme including two separated lobes (the N and C lobes). We have also shown conformational changes in IP5 2-K and have identified the residues involved in substrate recognition and catalysis. However, the specific features of mammalian IP5 2-Ks remain unknown. To this end, we report here the first structure for a murine IP5 2-K in complex with ATP/IP5 or IP6 Our structural findings indicated that the general folding in N and C lobes is conserved with AtIP5 2-K. A helical scaffold in the C lobe constitutes the inositol phosphate (IP)-binding site, which, along with the participation of the N lobe, endows high specificity to this protein. However, we also noted large structural differences between the orthologous from these two eukaryotic kingdoms. These differences include a novel zinc-binding site and regions unique to the mammalian IP5 2-K, as an unexpected basic patch on the protein surface. In conclusion, our findings have uncovered distinct features of a mammalian IP5 2-K and set the stage for investigations into protein-protein or protein-RNA interactions important for IP5 2-K function and activity. The Crystal Structure of Mammalian Inositol 1,3,4,5,6-Pentakisphosphate 2-Kinase Reveals a New Zinc Binding Site and Key Features for Protein Function.,Franco-Echevarria E, Sanz-Aparicio J, Brearley CA, Gonzalez-Rubio JM, Gonzalez B J Biol Chem. 2017 Apr 27. pii: jbc.M117.780395. doi: 10.1074/jbc.M117.780395. PMID:28450399[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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