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PDBsum entry 2i0e
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protein ligands Protein-protein interface(s) links
Transferase PDB id
2i0e

 

 

 

 

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Contents
Protein chains
329 a.a. *
302 a.a. *
Ligands
PDS ×2
Waters ×115
* Residue conservation analysis
PDB id:
2i0e
Name: Transferase
Title: Structure of catalytic domain of human protein kinasE C beta ii complexed with a bisindolylmaleimide inhibitor
Structure: Protein kinasE C-beta ii. Chain: a, b. Fragment: catalytic domain, residues 321-673. Engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Expressed in: spodoptera frugiperda. Expression_system_taxid: 7108.
Resolution:
2.60Å     R-factor:   0.237     R-free:   0.290
Authors: N.B.Grodsky,R.L.Love
Key ref: N.Grodsky et al. (2006). Structure of the catalytic domain of human protein kinase C beta II complexed with a bisindolylmaleimide inhibitor. Biochemistry, 45, 13970-13981. PubMed id: 17115692 DOI: 10.1021/bi061128h
Date:
10-Aug-06     Release date:   14-Nov-06    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
P05771  (KPCB_HUMAN) -  Protein kinase C beta type from Homo sapiens
Seq:
Struc: 		 
Seq:
Struc: 		671 a.a.
329 a.a.*
Protein chain
Pfam   ArchSchema ?
P05771  (KPCB_HUMAN) -  Protein kinase C beta type from Homo sapiens
Seq:
Struc: 		 
Seq:
Struc: 		671 a.a.
302 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 41 residue positions (black crosses)

 Enzyme reactions 
   Enzyme class: Chains A, B: E.C.2.7.11.13  - protein kinase C.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction:
1. L-seryl-[protein] + ATP = O-phospho-L-seryl-[protein] + ADP + H+
2. L-threonyl-[protein] + ATP = O-phospho-L-threonyl-[protein] + ADP + H+
L-seryl-[protein]
 + ATP
 = O-phospho-L-seryl-[protein]
 + ADP
 + H(+)
L-threonyl-[protein]
 + ATP
 = O-phospho-L-threonyl-[protein]
 + ADP
 + H(+)
Molecule diagrams generated from .mol files obtained from the KEGG ftp site

 

 
    reference    
 
 
DOI no: 10.1021/bi061128h Biochemistry 45:13970-13981 (2006)
PubMed id: 17115692  
 
 
Structure of the catalytic domain of human protein kinase C beta II complexed with a bisindolylmaleimide inhibitor.
N.Grodsky, Y.Li, D.Bouzida, R.Love, J.Jensen, B.Nodes, J.Nonomiya, S.Grant.
 
  ABSTRACT  
 
The conventional protein kinase C isoform, PKCII, is a signaling kinase activated during the hyperglycemic state and has been associated with the development of microvascular abnormalities associated with diabetes. PKCII, therefore, has been identified as a therapeutic target where inhibitors of its kinase activity are being pursued for treatment of microvascular-related diabetic complications. In this report, we describe the crystal structure of the catalytic domain of PKCbetaII complexed with an inhibitor at 2.6 A resolution. The kinase domain of PKCbetaII was cleaved and purified from full-length PKCbetaII expressed in baculovirus-infected insect cells. The overall kinase domain structure follows the classical bilobal fold and is in its fully activated conformation with three well-defined phosphorylated residues: Thr-500, Thr-641, and Ser-660. Different from the crystal structures of nonconventional PKC isoforms, the C-terminus of the PKCbetaII catalytic domain is almost fully ordered and features a novel alpha helix in the turn motif. An ATP-competitive inhibitor, 2-methyl-1H-indol-3-yl-BIM-1, was crystallized with the PKCbetaII catalytic domain as a dimer of two enzyme-inhibitor complexes. The bound inhibitor adopts a nonplanar conformation in the ATP-binding site, with the kinase domain taking on an intermediate, open conformation. This PKCbetaII-inhibitor complex represents the first structural description of any conventional PKC kinase domain. Given the pathogenic role of PKCbetaII in the development of diabetic complications, this structure can serve as a template for the rational design of inhibitors as potential therapeutic agents.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
21474065 N.Jura, X.Zhang, N.F.Endres, M.A.Seeliger, T.Schindler, and J.Kuriyan (2011).
Catalytic control in the EGF receptor and its connection to general kinase regulatory mechanisms.
  Mol Cell, 42, 9.  
21215369 T.A.Leonard, B.Różycki, L.F.Saidi, G.Hummer, and J.H.Hurley (2011).
Crystal structure and allosteric activation of protein kinase C βII.
  Cell, 144, 55-66.
PDB code: 3pfq
19934406 A.C.Newton (2010).
Protein kinase C: poised to signal.
  Am J Physiol Endocrinol Metab, 298, E395-E402.  
20094051 C.Rosse, M.Linch, S.Kermorgant, A.J.Cameron, K.Boeckeler, and P.J.Parker (2010).
PKC and the control of localized signal dynamics.
  Nat Rev Mol Cell Biol, 11, 103-112.  
20237675 J.van Ameijde, A.J.Poot, L.T.van Wandelen, A.E.Wammes, R.Ruijtenbeek, D.T.Rijkers, and R.M.Liskamp (2010).
Preparation of novel alkylated arginine derivatives suitable for click-cycloaddition chemistry and their incorporation into pseudosubstrate- and bisubstrate-based kinase inhibitors.
  Org Biomol Chem, 8, 1629-1639.  
20027184 L.R.Pearce, D.Komander, and D.R.Alessi (2010).
The nuts and bolts of AGC protein kinases.
  Nat Rev Mol Cell Biol, 11, 9.  
20188672 N.Hoshi, L.K.Langeberg, C.M.Gould, A.C.Newton, and J.D.Scott (2010).
Interaction with AKAP79 modifies the cellular pharmacology of PKC.
  Mol Cell, 37, 541-550.  
20445233 T.Takimura, K.Kamata, K.Fukasawa, H.Ohsawa, H.Komatani, T.Yoshizumi, I.Takahashi, H.Kotani, and Y.Iwasawa (2010).
Structures of the PKC-iota kinase domain in its ATP-bound and apo forms reveal defined structures of residues 533-551 in the C-terminal tail and their roles in ATP binding.
  Acta Crystallogr D Biol Crystallogr, 66, 577-583.
PDB codes: 3a8w 3a8x
19465915 A.J.Cameron, C.Escribano, A.T.Saurin, B.Kostelecky, and P.J.Parker (2009).
PKC maturation is promoted by nucleotide pocket occupation independently of intrinsic kinase activity.
  Nat Struct Mol Biol, 16, 624-630.  
19618415 A.J.Poot, J.van Ameijde, M.Slijper, A.van den Berg, R.Hilhorst, R.Ruijtenbeek, D.T.Rijkers, and R.M.Liskamp (2009).
Development of selective bisubstrate-based inhibitors against protein kinase C (PKC) isozymes by using dynamic peptide microarrays.
  Chembiochem, 10, 2042-2051.  
19091746 C.M.Gould, N.Kannan, S.S.Taylor, and A.C.Newton (2009).
The Chaperones Hsp90 and Cdc37 Mediate the Maturation and Stabilization of Protein Kinase C through a Conserved PXXP Motif in the C-terminal Tail.
  J Biol Chem, 284, 4921-4935.  
  18923184 S.F.Steinberg (2008).
Structural basis of protein kinase C isoform function.
  Physiol Rev, 88, 1341-1378.  
18566586 V.Facchinetti, W.Ouyang, H.Wei, N.Soto, A.Lazorchak, C.Gould, C.Lowry, A.C.Newton, Y.Mao, R.Q.Miao, W.C.Sessa, J.Qin, P.Zhang, B.Su, and E.Jacinto (2008).
The mammalian target of rapamycin complex 2 controls folding and stability of Akt and protein kinase C.
  EMBO J, 27, 1932-1943.  
17673466 H.Stensman, and C.Larsson (2007).
Identification of acidic amino acid residues in the protein kinase C alpha V5 domain that contribute to its insensitivity to diacylglycerol.
  J Biol Chem, 282, 28627-28638.  
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. Where a reference describes a PDB structure, the PDB code is shown on the right.

 

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