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Literature summary extracted from

  • Franco-Echevarria, E.; Sanz-Aparicio, J.; Brearley, C.A.; Gonzalez-Rubio, J.M.; Gonzalez, B.
    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 (2017), J. Biol. Chem., 292, 10534-10548 .
    View publication on PubMedView publication on EuropePMC

Crystallization (Commentary)

EC Number Crystallization (Comment) Organism
2.7.1.158 purified recombinant truncated enzyme lacking the 21 C-terminal residues (DELTAC-mIP5 2-K) in complex with IP5 and ATP or with IP6, X-ray diffraction structure determination and analysis at 2.4-3.2 A resolution. mIP5 2-K cyrstals are not obtained in the absence of inositide, structure for mIP5 2-K in the presence of one or both ligands, forming binary complexes (IP6) or ternary complexes Mus musculus

Protein Variants

EC Number Protein Variants Comment Organism
2.7.1.158 D437A site-directed mutagenesis, the mutant enzyme shows highly reduced activity Mus musculus
2.7.1.158 D439A site-directed mutagenesis, nearly inactive mutant enzyme Mus musculus
2.7.1.158 K138A site-directed mutagenesis, the mutant enzyme shows highly reduced activity Mus musculus

General Stability

EC Number General Stability Organism
2.7.1.158 the first bound Zn2+ ion, Zn1, is necessary for protein folding and stability Mus musculus

Metals/Ions

EC Number Metals/Ions Comment Organism Structure
2.7.1.158 Mg2+ required Mus musculus
2.7.1.158 Zn2+ mammalian IP5 2-Ks share a zinc-binding site with a distinct structure. Murine mIP5 2-K presents two zinc ions in its structure, one in the CIP-lobe (Zn1) and the other close to the hinge region (Zn2), binding structure, overview. The Zn1 site is formed by residues from two CIP lobe elements: Cys159, Cys162, and Cys181 from CIP-I and Cys291 from CIP-II. This site presents the typical zinc geometry and coordination. Zn1 is necessary for protein folding and stability Mus musculus

Natural Substrates/ Products (Substrates)

EC Number Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
2.7.1.158 ATP + 1D-myo-inositol 1,3,4,5,6-pentakisphosphate Mus musculus
-
 ADP + 1D-myo-inositol hexakisphosphate
-
 ?

Organism

EC Number Organism UniProt Comment Textmining
2.7.1.158 Mus musculus Q6P1C1
-
-

Substrates and Products (Substrate)

EC Number Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
2.7.1.158 ATP + 1D-myo-inositol 1,3,4,5,6-pentakisphosphate
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 Mus musculus ADP + 1D-myo-inositol hexakisphosphate
-
 ?
2.7.1.158 additional information mIP5 2-K active site and substrate recognition, overview. The adenine is strongly recognized through polar and hydrophobic interactions with both protein lobes and the hinge connecting them. In particular, it forms polar interactions with His14 and the backbones of Pro116 and Leu118. The ribose OHs interact with the C-lobe residues Glu136 and Arg209. The triphosphate moiety is tightly bound to the N-lobe of the enzyme through polar interactions and to the C-lobe through two magnesium ions. In particular, phosphate interaction with residue Arg-33, with a flexible loop (G-loop, residues Gly15-Ser20) and with an acidic residue (Asp437) through the magnesium ions, is conserved throughout the PK superfamily and is essential for nucleotide binding and kinase activity Mus musculus ?
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-

Subunits

EC Number Subunits Comment Organism
2.7.1.158 More mouse IP5 2-K folds in two lobes, N- and C-terminal lobes, connected by a hinge, thereby conserving the general fold scheme of PKs and IPKs, and in a similar way, both lobes coordinate the nucleotide between them. The N-lobe core forms a beta-sheet from five antiparallel beta-strands (beta1-beta5) showing two helical segments. The first helical segment (N-I) harbors alpha1, equivalent to the helix alphaC characterized in all protein kinases, whereas the second one (N-II) is a specific insertion different in every IPK subfamily. Structure comparisons Mus musculus

Synonyms

EC Number Synonyms Comment Organism
2.7.1.158 inositol 1,3,4,5,6-pentakisphosphate 2-kinase
-
 Mus musculus
2.7.1.158 IP5 2-K
-
 Mus musculus
2.7.1.158 mIP5 2-K
-
 Mus musculus

Cofactor

EC Number Cofactor Comment Organism Structure
2.7.1.158 ATP
-
 Mus musculus

General Information

EC Number General Information Comment Organism
2.7.1.158 evolution most residues involved in substrate binding and catalysis are conserved between mammal and plant IP5 2-Ks, but some differences in the inositide P1 and P3 coordination are observed. InmIP5 2-K, additional interactions with P1 are produced through the side chain of Lys173, a residue non-conserved with the plant IP5 2-Ks but absolutely conserved in mammal enzymes, whereas conservative substitutions can be observed in other vertebrates Mus musculus