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PDBsum entry 1mrv
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Transferase PDB id
1mrv

 

 

 

 

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Contents
Protein chain
261 a.a. *
Waters ×74
* Residue conservation analysis
PDB id:
1mrv
Name: Transferase
Title: Crystal structure of an inactive akt2 kinase domain
Structure: Rac-beta serine/threonine kinase. Chain: a. Fragment: kinase domain. Synonym: rac-pk-beta. Protein kinase akt-2. Protein kinase b, beta. Pkb beta. Engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Gene: akt2. Expressed in: spodoptera frugiperda. Expression_system_taxid: 7108.
Resolution:
2.80Å     R-factor:   0.247     R-free:   0.295
Authors: X.Huang,M.Begley,K.A.Morgenstern,Y.Gu,P.Rose,H.Zhao,X.Zhu
Key ref:
X.Huang et al. (2003). Crystal structure of an inactive Akt2 kinase domain. Structure, 11, 21-30. PubMed id: 12517337 DOI: 10.1016/S0969-2126(02)00937-1
Date:
18-Sep-02     Release date:   23-Sep-03    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
P31751  (AKT2_HUMAN) -  RAC-beta serine/threonine-protein kinase from Homo sapiens
Seq:
Struc: 		481 a.a.
261 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class: E.C.2.7.11.1  - non-specific serine/threonine protein kinase.
[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: 10.1016/S0969-2126(02)00937-1 Structure 11:21-30 (2003)
PubMed id: 12517337  
 
 
Crystal structure of an inactive Akt2 kinase domain.
X.Huang, M.Begley, K.A.Morgenstern, Y.Gu, P.Rose, H.Zhao, X.Zhu.
 
  ABSTRACT  
 
Akt/PKB represents a subfamily of three isoforms from the AGC serine/threonine kinase family. Amplification of Akt activity has been implicated in diseases that involve inappropriate cell survival, including a number of human malignancies. The structure of an inactive and unliganded Akt2 kinase domain reveals several features that distinguish it from other kinases. Most of the alpha helix C is disordered. The activation loop in this structure adopts a conformation that appears to sterically hinder the binding of both ATP and peptide substrate. In addition, an intramolecular disulfide bond is observed between two cysteines in the activation loop. Residues within the linker region between the N- and C-terminal lobes also contribute to the inactive conformation by partially occupying the ATP binding site.
 
  Selected figure(s)  
 
Figure 1.
Figure 1. Structure of the Kinase Domain of Unphosphorylated Akt2(A) Ribbon diagram showing the overall fold of the Akt2 kinase domain.(B) Backbone trace of Akt2 and PKA in which the Ca atoms of the a-helical cores are superposed. Akt2, blue; PKA, red. The Cas of PKA in the closed conformation in the ternary complex is used here. (A) was prepared with MOLSCRIPT, and (B) was prepared with GRASP.
 
  The above figure is reprinted by permission from Cell Press: Structure (2003, 11, 21-30) copyright 2003.  
  Figure was selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
20624032 M.C.van den Berg, and B.M.Burgering (2011).
Integrating opposing signals toward Forkhead box O.
  Antioxid Redox Signal, 14, 607-621.  
20626320 P.L.de Keizer, B.M.Burgering, and T.B.Dansen (2011).
Forkhead box o as a sensor, mediator, and regulator of redox signaling.
  Antioxid Redox Signal, 14, 1093-1106.  
19965870 J.M.Steichen, G.H.Iyer, S.Li, S.A.Saldanha, M.S.Deal, V.L.Woods, and S.S.Taylor (2010).
Global consequences of activation loop phosphorylation on protein kinase A.
  J Biol Chem, 285, 3825-3832.  
20886116 W.I.Wu, W.C.Voegtli, H.L.Sturgis, F.P.Dizon, G.P.Vigers, and B.J.Brandhuber (2010).
Crystal structure of human AKT1 with an allosteric inhibitor reveals a new mode of kinase inhibition.
  PLoS One, 5, e12913.
PDB code: 3o96
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.  
19462409 M.Guo, B.X.Huang, and H.Y.Kim (2009).
Conformational changes in Akt1 activation probed by amide hydrogen/deuterium exchange and nano-electrospray ionization mass spectrometry.
  Rapid Commun Mass Spectrom, 23, 1885-1891.  
19723632 R.Dettori, S.Sonzogni, L.Meyer, L.A.Lopez-Garcia, N.A.Morrice, S.Zeuzem, M.Engel, A.Piiper, S.Neimanis, M.Frödin, and R.M.Biondi (2009).
Regulation of the interaction between protein kinase C-related protein kinase 2 (PRK2) and its upstream kinase, 3-phosphoinositide-dependent protein kinase 1 (PDK1).
  J Biol Chem, 284, 30318-30327.  
19651772 R.Scholz, M.Suter, T.Weimann, C.Polge, P.V.Konarev, R.F.Thali, R.D.Tuerk, B.Viollet, T.Wallimann, U.Schlattner, and D.Neumann (2009).
Homo-oligomerization and activation of AMP-activated protein kinase are mediated by the kinase domain alphaG-helix.
  J Biol Chem, 284, 27425-27437.  
19598234 S.W.Fan, R.A.George, N.L.Haworth, L.L.Feng, J.Y.Liu, and M.A.Wouters (2009).
Conformational changes in redox pairs of protein structures.
  Protein Sci, 18, 1745-1765.  
19568789 V.Calleja, M.Laguerre, and B.Larijani (2009).
3-D structure and dynamics of protein kinase B-new mechanism for the allosteric regulation of an AGC kinase.
  J Chem Biol, 2, 11-25.  
19718043 V.Hindie, A.Stroba, H.Zhang, L.A.Lopez-Garcia, L.Idrissova, S.Zeuzem, D.Hirschberg, F.Schaeffer, T.J.Jørgensen, M.Engel, P.M.Alzari, and R.M.Biondi (2009).
Structure and allosteric effects of low-molecular-weight activators on the protein kinase PDK1.
  Nat Chem Biol, 5, 758-764.
PDB codes: 3hrc 3hrf
18722498 C.Volonté, N.D'Ambrosi, and S.Amadio (2008).
Protein cooperation: from neurons to networks.
  Prog Neurobiol, 86, 61-71.  
17186497 B.Venkatesan, L.Mahimainathan, F.Das, N.Ghosh-Choudhury, and G.Ghosh Choudhury (2007).
Downregulation of catalase by reactive oxygen species via PI 3 kinase/Akt signaling in mesangial cells.
  J Cell Physiol, 211, 457-467.  
17965184 B.Zhao, R.Lehr, A.M.Smallwood, T.F.Ho, K.Maley, T.Randall, M.S.Head, K.K.Koretke, and C.G.Schnackenberg (2007).
Crystal structure of the kinase domain of serum and glucocorticoid-regulated kinase 1 in complex with AMP PNP.
  Protein Sci, 16, 2761-2769.
PDB code: 2r5t
17386267 J.Brognard, E.Sierecki, T.Gao, and A.C.Newton (2007).
PHLPP and a second isoform, PHLPP2, differentially attenuate the amplitude of Akt signaling by regulating distinct Akt isoforms.
  Mol Cell, 25, 917-931.  
17965187 M.Ikuta, M.Kornienko, N.Byrne, J.C.Reid, S.Mizuarai, H.Kotani, and S.K.Munshi (2007).
Crystal structures of the N-terminal kinase domain of human RSK1 bound to three different ligands: Implications for the design of RSK1 specific inhibitors.
  Protein Sci, 16, 2626-2635.
PDB codes: 2z7q 2z7r 2z7s
17407381 V.Calleja, D.Alcor, M.Laguerre, J.Park, B.Vojnovic, B.A.Hemmings, J.Downward, P.J.Parker, and B.Larijani (2007).
Intramolecular and intermolecular interactions of protein kinase B define its activation in vivo.
  PLoS Biol, 5, e95.  
17822369 W.Malorni, I.Campesi, E.Straface, S.Vella, and F.Franconi (2007).
Redox features of the cell: a gender perspective.
  Antioxid Redox Signal, 9, 1779-1801.  
17084073 M.G.Gold, D.Barford, and D.Komander (2006).
Lining the pockets of kinases and phosphatases.
  Curr Opin Struct Biol, 16, 693-701.  
16987030 N.R.Leslie (2006).
The redox regulation of PI 3-kinase-dependent signaling.
  Antioxid Redox Signal, 8, 1765-1774.  
16972266 Y.J.Lee, J.H.Lee, and H.J.Han (2006).
Extracellular adenosine triphosphate protects oxidative stress-induced increase of p21(WAF1/Cip1) and p27(Kip1) expression in primary cultured renal proximal tubule cells: role of PI3K and Akt signaling.
  J Cell Physiol, 209, 802-810.  
16549430 Y.Urata, Y.Ihara, H.Murata, S.Goto, T.Koji, J.Yodoi, S.Inoue, and T.Kondo (2006).
17Beta-estradiol protects against oxidative stress-induced cell death through the glutathione/glutaredoxin-dependent redox regulation of Akt in myocardiac H9c2 cells.
  J Biol Chem, 281, 13092-13102.  
16288296 C.C.Kumar, and V.Madison (2005).
AKT crystal structure and AKT-specific inhibitors.
  Oncogene, 24, 7493-7501.  
16288287 K.Du, and P.N.Tsichlis (2005).
Regulation of the Akt kinase by interacting proteins.
  Oncogene, 24, 7401-7409.  
16221682 R.C.Hresko, and M.Mueckler (2005).
mTOR.RICTOR is the Ser473 kinase for Akt/protein kinase B in 3T3-L1 adipocytes.
  J Biol Chem, 280, 40406-40416.  
15274926 K.J.Smith, P.S.Carter, A.Bridges, P.Horrocks, C.Lewis, G.Pettman, A.Clarke, M.Brown, J.Hughes, M.Wilkinson, B.Bax, and A.Reith (2004).
The structure of MSK1 reveals a novel autoinhibitory conformation for a dual kinase protein.
  Structure, 12, 1067-1077.
PDB code: 1vzo
  15150572 S.Hövelmann, T.L.Beckers, and M.Schmidt (2004).
Molecular alterations in apoptotic pathways after PKB/Akt-mediated chemoresistance in NCI H460 cells.
  Br J Cancer, 90, 2370-2377.  
14522978 H.Murata, Y.Ihara, H.Nakamura, J.Yodoi, K.Sumikawa, and T.Kondo (2003).
Glutaredoxin exerts an antiapoptotic effect by regulating the redox state of Akt.
  J Biol Chem, 278, 50226-50233.  
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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