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PDBsum entry 1tbn
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Calcium-binding protein PDB id
1tbn

 

 

 

 

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Contents
Protein chain
66 a.a. *
Metals
_ZN ×2
* Residue conservation analysis
PDB id:
1tbn
Name: Calcium-binding protein
Title: Nmr structure of a protein kinasE C-g phorbol-binding domain, minimized average structure
Structure: Protein kinasE C, gamma type. Chain: a. Fragment: cys2 domain. Synonym: rat brain pkc-g. Engineered: yes
Source: Rattus rattus. Black rat. Organism_taxid: 10117. Organ: brain. Expressed in: escherichia coli bl21. Expression_system_taxid: 511693.
NMR struc: 1 models
Authors: R.X.Xu,T.Pawelczyk,T.Xia,S.C.Brown
Key ref:
R.X.Xu et al. (1997). NMR structure of a protein kinase C-gamma phorbol-binding domain and study of protein-lipid micelle interactions. Biochemistry, 36, 10709-10717. PubMed id: 9271501 DOI: 10.1021/bi970833a
Date:
15-Apr-97     Release date:   29-Apr-98    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
P63319  (KPCG_RAT) -  Protein kinase C gamma type from Rattus norvegicus
Seq:
Struc: 		 
Seq:
Struc: 		697 a.a.
66 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class: 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/bi970833a Biochemistry 36:10709-10717 (1997)
PubMed id: 9271501  
 
 
NMR structure of a protein kinase C-gamma phorbol-binding domain and study of protein-lipid micelle interactions.
R.X.Xu, T.Pawelczyk, T.H.Xia, S.C.Brown.
 
  ABSTRACT  
 
Classical protein kinase C (PKC) family members are activated by the binding of various ligands to one of several cysteine-rich domains of the enzyme. The natural agonist, diacylglycerol (DAG), and the natural product superagonist, phorbol dibutyrate (PDB), activate the enzyme to produce wide-ranging physiological effects. The second cysteine-rich (Cys2) domain of rat brain PKC-gamma was expressed and labeled with 15N and 13C, and the solution structure was determined to high resolution using multidimensional heteronuclear NMR methods. The phorbol binding site was identified by titrating this domain with phorbol-12,13-dibutyrate (PDB) in the presence of organic cosolvents. Titrations of this domain with lipid micelles, in the absence and presence of phorbols, indicate selective broadening of some resonances. The observed behavior indicates conformational exchange between bound and free states upon protein-micelle interaction. The data also suggest that half of the domain, including the phorbol site and one of the zinc sites, is capable of inserting into membranes.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
21419781 M.D.Stewart, B.Morgan, F.Massi, and T.I.Igumenova (2011).
Probing the determinants of diacylglycerol binding affinity in the C1B domain of protein kinase Cα.
  J Mol Biol, 408, 949-970.  
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
18505819 C.A.Farah, I.Nagakura, D.Weatherill, X.Fan, and W.S.Sossin (2008).
Physiological role for phosphatidic acid in the translocation of the novel protein kinase C Apl II in Aplysia neurons.
  Mol Cell Biol, 28, 4719-4733.  
18707088 S.El Kazzouli, N.E.Lewin, P.M.Blumberg, and V.E.Marquez (2008).
Conformationally constrained analogues of diacylglycerol. 30. An investigation of diacylglycerol-lactones containing heteroaryl groups reveals compounds with high selectivity for Ras guanyl nucleotide-releasing proteins.
  J Med Chem, 51, 5371-5386.  
  18923184 S.F.Steinberg (2008).
Structural basis of protein kinase C isoform function.
  Physiol Rev, 88, 1341-1378.  
17603894 A.L.Lomize, I.D.Pogozheva, M.A.Lomize, and H.I.Mosberg (2007).
The role of hydrophobic interactions in positioning of peripheral proteins in membranes.
  BMC Struct Biol, 7, 44.  
17493614 D.Lin, D.Shanks, O.Prakash, and D.J.Takemoto (2007).
Protein kinase C gamma mutations in the C1B domain cause caspase-3-linked apoptosis in lens epithelial cells through gap junctions.
  Exp Eye Res, 85, 113-122.  
17071619 D.R.Dries, L.L.Gallegos, and A.C.Newton (2007).
A single residue in the C1 domain sensitizes novel protein kinase C isoforms to cellular diacylglycerol production.
  J Biol Chem, 282, 826-830.  
17500509 H.Al-Ali, T.J.Ragan, X.Gao, and T.K.Harris (2007).
Reconstitution of modular PDK1 functions on trans-splicing of the regulatory PH and catalytic kinase domains.
  Bioconjug Chem, 18, 1294-1302.  
17697049 Y.Shirai, T.Murakami, M.Kuramasu, L.Iijima, and N.Saito (2007).
A novel PIP2 binding of epsilonPKC and its contribution to the neurite induction ability.
  J Neurochem, 102, 1635-1644.  
16698549 E.Harjes, S.Harjes, S.Wohlgemuth, K.H.Müller, E.Krieger, C.Herrmann, and P.Bayer (2006).
GTP-Ras disrupts the intramolecular complex of C1 and RA domains of Nore1.
  Structure, 14, 881-888.
PDB code: 2fnf
16943444 J.Das, X.Zhou, and K.W.Miller (2006).
Identification of an alcohol binding site in the first cysteine-rich domain of protein kinase Cdelta.
  Protein Sci, 15, 2107-2119.  
16616874 J.H.Hurley (2006).
Membrane binding domains.
  Biochim Biophys Acta, 1761, 805-811.  
15642736 D.Lin, and D.J.Takemoto (2005).
Oxidative activation of protein kinase Cgamma through the C1 domain. Effects on gap junctions.
  J Biol Chem, 280, 13682-13693.  
16041745 K.Irie, Y.Nakagawa, and H.Ohigashi (2005).
Toward the development of new medicinal leads with selectivity for protein kinase C isozymes.
  Chem Rec, 5, 185-195.  
15718244 M.Ling, U.Trollér, R.Zeidman, H.Stensman, A.Schultz, and C.Larsson (2005).
Identification of conserved amino acids N-terminal of the PKC epsilon C1b domain crucial for protein kinase C epsilon-mediated induction of neurite outgrowth.
  J Biol Chem, 280, 17910-17919.  
16079140 R.V.Stahelin, J.Wang, N.R.Blatner, J.D.Rafter, D.Murray, and W.Cho (2005).
The origin of C1A-C2 interdomain interactions in protein kinase Calpha.
  J Biol Chem, 280, 36452-36463.  
15869386 W.Cho, and R.V.Stahelin (2005).
Membrane-protein interactions in cell signaling and membrane trafficking.
  Annu Rev Biophys Biomol Struct, 34, 119-151.  
15507211 B.Canagarajah, F.C.Leskow, J.Y.Ho, H.Mischak, L.F.Saidi, M.G.Kazanietz, and J.H.Hurley (2004).
Structural mechanism for lipid activation of the Rac-specific GAP, beta2-chimaerin.
  Cell, 119, 407-418.
PDB code: 1xa6
15576038 M.D.Tibbetts, E.N.Shiozaki, L.Gu, E.R.McDonald, W.S.El-Deiry, and Y.Shi (2004).
Crystal structure of a FYVE-type zinc finger domain from the caspase regulator CARP2.
  Structure, 12, 2257-2263.
PDB code: 1y02
15064353 S.Carrasco, and I.Merida (2004).
Diacylglycerol-dependent binding recruits PKCtheta and RasGRP1 C1 domains to specific subcellular localizations in living T lymphocytes.
  Mol Biol Cell, 15, 2932-2942.  
15459208 T.A.Nguyen, L.J.Takemoto, and D.J.Takemoto (2004).
Inhibition of gap junction activity through the release of the C1B domain of protein kinase Cgamma (PKCgamma) from 14-3-3: identification of PKCgamma-binding sites.
  J Biol Chem, 279, 52714-52725.  
12954613 B.Ananthanarayanan, R.V.Stahelin, M.A.Digman, and W.Cho (2003).
Activation mechanisms of conventional protein kinase C isoforms are determined by the ligand affinity and conformational flexibility of their C1 domains.
  J Biol Chem, 278, 46886-46894.  
12644968 D.H.Chen, Z.Brkanac, C.L.Verlinde, X.J.Tan, L.Bylenok, D.Nochlin, M.Matsushita, H.Lipe, J.Wolff, M.Fernandez, P.J.Cimino, T.D.Bird, and W.H.Raskind (2003).
Missense mutations in the regulatory domain of PKC gamma: a new mechanism for dominant nonepisodic cerebellar ataxia.
  Am J Hum Genet, 72, 839-849.  
12621060 M.Shindo, K.Irie, A.Masuda, H.Ohigashi, Y.Shirai, K.Miyasaka, and N.Saito (2003).
Synthesis and phorbol ester binding of the cysteine-rich domains of diacylglycerol kinase (DGK) isozymes. DGKgamma and DGKbeta are new targets of tumor-promoting phorbol esters.
  J Biol Chem, 278, 18448-18454.  
12191619 K.Irie, A.Nakahara, Y.Nakagawa, H.Ohigashi, M.Shindo, H.Fukuda, H.Konishi, U.Kikkawa, K.Kashiwagi, and N.Saito (2002).
Establishment of a binding assay for protein kinase C isozymes using synthetic C1 peptides and development of new medicinal leads with protein kinase C isozyme and C1 domain selectivity.
  Pharmacol Ther, 93, 271-281.  
11956218 Y.Yang, L.Li, G.W.Wong, S.A.Krilis, M.S.Madhusudhan, A.Sali, and R.L.Stevens (2002).
RasGRP4, a new mast cell-restricted Ras guanine nucleotide-releasing protein with calcium- and diacylglycerol-binding motifs. Identification of defective variants of this signaling protein in asthma, mastocytosis, and mast cell leukemia patients and demonstration of the importance of RasGRP4 in mast cell development and function.
  J Biol Chem, 277, 25756-25774.  
11292843 N.V.Grishin (2001).
Treble clef finger--a functionally diverse zinc-binding structural motif.
  Nucleic Acids Res, 29, 1703-1714.  
10940243 J.H.Hurley, and S.Misra (2000).
Signaling and subcellular targeting by membrane-binding domains.
  Annu Rev Biophys Biomol Struct, 29, 49-79.  
10391930 M.Medkova, and W.Cho (1999).
Interplay of C1 and C2 domains of protein kinase C-alpha in its membrane binding and activation.
  J Biol Chem, 274, 19852-19861.  
10090770 S.J.Slater, S.K.Milano, B.A.Stagliano, K.J.Gergich, C.Ho, A.Mazurek, F.J.Taddeo, M.B.Kelly, M.D.Yeager, and C.D.Stubbs (1999).
Synergistic activation of protein kinase Calpha, -betaI, and -gamma isoforms induced by diacylglycerol and phorbol ester: roles of membrane association and activating conformational changes.
  Biochemistry, 38, 3804-3815.  
10367894 S.Misra, and J.H.Hurley (1999).
Crystal structure of a phosphatidylinositol 3-phosphate-specific membrane-targeting motif, the FYVE domain of Vps27p.
  Cell, 97, 657-666.
PDB code: 1vfy
9724512 J.E.Johnson, M.L.Zimmerman, D.L.Daleke, and A.C.Newton (1998).
Lipid structure and not membrane structure is the major determinant in the regulation of protein kinase C by phosphatidylserine.
  Biochemistry, 37, 12020-12025.  
  9774683 M.Daub, J.Jöckel, T.Quack, C.K.Weber, F.Schmitz, U.R.Rapp, A.Wittinghofer, and C.Block (1998).
The RafC1 cysteine-rich domain contains multiple distinct regulatory epitopes which control Ras-dependent Raf activation.
  Mol Cell Biol, 18, 6698-6710.  
9538007 M.Medkova, and W.Cho (1998).
Differential membrane-binding and activation mechanisms of protein kinase C-alpha and -epsilon.
  Biochemistry, 37, 4892-4900.  
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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