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PDBsum entry 2uvm
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Contents |
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* Residue conservation analysis
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PDB id:
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Transferase
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Title:
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Structure of pkbalpha ph domain in complex with a novel inositol headgroup surrogate, benzene 1,2,3,4-tetrakisphosphate
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Structure:
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Rac-alpha serine/threonine-protein kinase. Chain: a. Fragment: pleckstrin homology (ph) domain, residues 1-123. Synonym: protein kinase b alpha, rac-pk-alpha, protein kinase b, pkb, c-akt. Engineered: yes
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Source:
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Homo sapiens. Human. Organism_taxid: 9606. Expressed in: escherichia coli. Expression_system_taxid: 511693.
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Resolution:
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1.94Å
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R-factor:
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0.252
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R-free:
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0.269
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Authors:
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D.Komander,S.J.Mills,M.N.Trusselle,S.T.Safrany,D.M.F.Van Aalten, B.V.L.Potter
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Key ref:
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S.J.Mills
et al.
(2007).
Novel inositol phospholipid headgroup surrogate crystallized in the pleckstrin homology domain of protein kinase Balpha.
Acs Chem Biol,
2,
242-246.
PubMed id:
DOI:
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Date:
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12-Mar-07
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Release date:
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17-Apr-07
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PROCHECK
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Headers
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References
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P31749
(AKT1_HUMAN) -
RAC-alpha serine/threonine-protein kinase from Homo sapiens
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Seq:
Struc:
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480 a.a.
116 a.a.
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Key: |
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PfamA domain |
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Secondary structure |
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CATH domain |
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Enzyme class:
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E.C.2.7.11.1
- non-specific serine/threonine protein kinase.
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Reaction:
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1.
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L-seryl-[protein] + ATP = O-phospho-L-seryl-[protein] + ADP + H+
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2.
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L-threonyl-[protein] + ATP = O-phospho-L-threonyl-[protein] + ADP + H+
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L-seryl-[protein]
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+
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ATP
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=
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O-phospho-L-seryl-[protein]
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+
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ADP
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+
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H(+)
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L-threonyl-[protein]
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+
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ATP
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=
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O-phospho-L-threonyl-[protein]
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+
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ADP
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+
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H(+)
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Molecule diagrams generated from .mol files obtained from the
KEGG ftp site
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DOI no:
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Acs Chem Biol
2:242-246
(2007)
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PubMed id:
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Novel inositol phospholipid headgroup surrogate crystallized in the pleckstrin homology domain of protein kinase Balpha.
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S.J.Mills,
D.Komander,
M.N.Trusselle,
S.T.Safrany,
D.M.van Aalten,
B.V.Potter.
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ABSTRACT
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Protein kinase B (PKB/Akt) plays a key role in cell signaling. The PH domain of
PKB binds phosphatidylinositol 3,4,5-trisphosphate translocating PKB to the
plasma membrane for activation by 3-phosphoinositide-dependent protein kinase 1.
The crystal structure of the headgroup inositol 1,3,4,5-tetrakisphosphate
Ins(1,3,4,5)P4-PKB complex facilitates in silico ligand design. The novel
achiral analogue benzene 1,2,3,4-tetrakisphosphate (Bz(1,2,3,4)P4) possesses
phosphate regiochemistry different from that of Ins(1,3,4,5)P4 and surprisingly
binds with similar affinity as the natural headgroup. Bz(1,2,3,4)P4
co-crystallizes with the PKBalpha PH domain in a fashion also predictable in
silico. The 2-phosphate of Bz(1,2,3,4)P4 does not interact with any residue, and
the D5-phosphate of Ins(1,3,4,5)P4 is not mimicked by Bz(1,2,3,4)P4.
Bz(1,2,3,4)P4 is an example of a simple inositol phosphate surrogate
crystallized in a protein, and this approach could be applied to design
modulators of inositol polyphosphate binding proteins.
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Literature references that cite this PDB file's key reference
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PubMed id
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Reference
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M.D.Best,
H.Zhang,
and
G.D.Prestwich
(2010).
Inositol polyphosphates, diphosphoinositol polyphosphates and phosphatidylinositol polyphosphate lipids: structure, synthesis, and development of probes for studying biological activity.
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Nat Prod Rep,
27,
1403-1430.
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M.Falasca,
D.Chiozzotto,
H.Y.Godage,
M.Mazzoletti,
A.M.Riley,
S.Previdi,
B.V.Potter,
M.Broggini,
and
T.Maffucci
(2010).
A novel inhibitor of the PI3K/Akt pathway based on the structure of inositol 1,3,4,5,6-pentakisphosphate.
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Br J Cancer,
102,
104-114.
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L.Du-Cuny,
Z.Song,
S.Moses,
G.Powis,
E.A.Mash,
E.J.Meuillet,
and
S.Zhang
(2009).
Computational modeling of novel inhibitors targeting the Akt pleckstrin homology domain.
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Bioorg Med Chem,
17,
6983-6992.
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S.J.Mills,
F.Vandeput,
M.N.Trusselle,
S.T.Safrany,
C.Erneux,
and
B.V.Potter
(2008).
Benzene polyphosphates as tools for cell signalling: inhibition of inositol 1,4,5-trisphosphate 5-phosphatase and interaction with the PH domain of protein kinase Balpha.
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Chembiochem,
9,
1757-1766.
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The most recent references are shown first.
Citation data come partly from CiteXplore and partly
from an automated harvesting procedure. Note that this is likely to be
only a partial list as not all journals are covered by
either method. However, we are continually building up the citation data
so more and more references will be included with time.
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Links
