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PDBsum entry 1bx6
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protein ligands links
Serine/threonine-protein kinase PDB id
1bx6

 

 

 

 

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Contents
Protein chain
339 a.a. *
Ligands
BA1
Waters ×305
* Residue conservation analysis
PDB id:
1bx6
Name: Serine/threonine-protein kinase
Title: Crystal structure of the potent natural product inhibitor balanol in complex with the catalytic subunit of camp-dependent protein kinase
Structure: Camp-dependent protein kinase. Chain: a. Fragment: catalytic domain. Synonym: capk or pka. Engineered: yes
Source: Mus musculus. House mouse. Organism_taxid: 10090. Expressed in: escherichia coli. Expression_system_taxid: 562
Resolution:
2.10Å     R-factor:   0.210     R-free:   0.340
Authors: N.Narayana,N.-H.Xuong,L.F.Ten Eyck,S.S.Taylor
Key ref:
N.Narayana et al. (1999). Crystal structure of the potent natural product inhibitor balanol in complex with the catalytic subunit of cAMP-dependent protein kinase. Biochemistry, 38, 2367-2376. PubMed id: 10029530 DOI: 10.1021/bi9820659
Date:
13-Oct-98     Release date:   27-Apr-99    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
P05132  (KAPCA_MOUSE) -  cAMP-dependent protein kinase catalytic subunit alpha from Mus musculus
Seq:
Struc: 		351 a.a.
339 a.a.*
Key:    Secondary structure  CATH domain
* PDB and UniProt seqs differ at 1 residue position (black cross)

 Enzyme reactions 
   Enzyme class: E.C.2.7.11.11  - cAMP-dependent 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: 10.1021/bi9820659 Biochemistry 38:2367-2376 (1999)
PubMed id: 10029530  
 
 
Crystal structure of the potent natural product inhibitor balanol in complex with the catalytic subunit of cAMP-dependent protein kinase.
N.Narayana, T.C.Diller, K.Koide, M.E.Bunnage, K.C.Nicolaou, L.L.Brunton, N.H.Xuong, L.F.Ten Eyck, S.S.Taylor.
 
  ABSTRACT  
 
Endogenous protein kinase inhibitors are essential for a wide range of physiological functions. These endogenous inhibitors may mimic peptide substrates as in the case of the heat-stable protein kinase inhibitor (PKI), or they may mimic nucleotide triphosphates. Natural product inhibitors, endogenous to the unique organisms producing them, can be potent exogenous inhibitors against foreign protein kinases. Balanol is a natural product inhibitor exhibiting low nanomolar Ki values against serine and threonine specific kinases, while being ineffective against protein tyrosine kinases. To elucidate balanol's specific inhibitory effects and provide a basis for understanding inhibition-regulated biological processes, a 2.1 A resolution crystal structure of balanol in complex with cAMP-dependent protein kinase (cAPK) was determined. The structure reveals conserved binding regions and displays extensive complementary interactions between balanol and conserved cAPK residues. This report describes the structure of a protein kinase crystallized with a natural ATP mimetic in the absence of metal ions and peptide inhibitor.
 

Literature references that cite this PDB file's key reference Google scholar

  PubMed id Reference
19934406 A.C.Newton (2010).
Protein kinase C: poised to signal.
  Am J Physiol Endocrinol Metab, 298, E395-E402.  
20128603 J.J.Tesmer, V.M.Tesmer, D.T.Lodowski, H.Steinhagen, and J.Huber (2010).
Structure of human G protein-coupled receptor kinase 2 in complex with the kinase inhibitor balanol.
  J Med Chem, 53, 1867-1870.
PDB codes: 3cik 3krw 3krx
19551802 H.Decornez, A.Gulyás-Forró, A.Papp, M.Szabó, G.Sármay, I.Hajdú, S.Cseh, G.Dormán, and D.B.Kitchen (2009).
Design, selection, and evaluation of a general kinase-focused library.
  ChemMedChem, 4, 1273-1278.  
18711718 Z.Huang, and C.F.Wong (2009).
Conformational selection of protein kinase A revealed by flexible-ligand flexible-protein docking.
  J Comput Chem, 30, 631-644.  
19845408 Z.Huang, and C.F.Wong (2009).
Docking flexible peptide to flexible protein by molecular dynamics using two implicit-solvent models: an evaluation in protein kinase and phosphatase systems.
  J Phys Chem B, 113, 14343-14354.  
17957770 Z.Huang, C.F.Wong, and R.A.Wheeler (2008).
Flexible protein-flexible ligand docking with disrupted velocity simulated annealing.
  Proteins, 71, 440-454.  
17228977 M.Wang, and C.F.Wong (2007).
Rank-ordering protein-ligand binding affinity by a quantum mechanics/molecular mechanics/Poisson-Boltzmann-surface area model.
  J Chem Phys, 126, 026101.  
16245317 C.F.Wong, J.Kua, Y.Zhang, T.P.Straatsma, and J.A.McCammon (2005).
Molecular docking of balanol to dynamics snapshots of protein kinase A.
  Proteins, 61, 850-858.  
15731862 J.López-Prados, F.Cuevas, N.C.Reichardt, J.L.de Paz, E.Q.Morales, and M.Martín-Lomas (2005).
Design and synthesis of inositolphosphoglycan putative insulin mediators.
  Org Biomol Chem, 3, 764-786.  
16253959 J.Wu, J.Yang, N.Kannan, Madhusudan, N.H.Xuong, L.F.Ten Eyck, and S.S.Taylor (2005).
Crystal structure of the E230Q mutant of cAMP-dependent protein kinase reveals an unexpected apoenzyme conformation and an extended N-terminal A helix.
  Protein Sci, 14, 2871-2879.
PDB code: 1syk
14962382 D.Komander, G.S.Kular, A.W.Schüttelkopf, M.Deak, K.R.Prakash, J.Bain, M.Elliott, M.Garrido-Franco, A.P.Kozikowski, D.R.Alessi, and D.M.van Aalten (2004).
Interactions of LY333531 and other bisindolyl maleimide inhibitors with PDK1.
  Structure, 12, 215-226.
PDB codes: 1uu3 1uu7 1uu8 1uu9 1uvr
14996846 M.Gassel, C.B.Breitenlechner, N.König, R.Huber, R.A.Engh, and D.Bossemeyer (2004).
The protein kinase C inhibitor bisindolyl maleimide 2 binds with reversed orientations to different conformations of protein kinase A.
  J Biol Chem, 279, 23679-23690.
PDB code: 1szm
15185335 P.A.Sims, C.F.Wong, and J.A.McCammon (2004).
Charge optimization of the interface between protein kinases and their ligands.
  J Comput Chem, 25, 1416-1429.  
14656443 C.Breitenlechner, M.Gassel, H.Hidaka, V.Kinzel, R.Huber, R.A.Engh, and D.Bossemeyer (2003).
Protein kinase A in complex with Rho-kinase inhibitors Y-27632, Fasudil, and H-1152P: structural basis of selectivity.
  Structure, 11, 1595-1607.
PDB codes: 1q8t 1q8u 1q8w
12517337 X.Huang, M.Begley, K.A.Morgenstern, Y.Gu, P.Rose, H.Zhao, and X.Zhu (2003).
Crystal structure of an inactive Akt2 kinase domain.
  Structure, 11, 21-30.
PDB codes: 1mrv 1mry
12191603 R.A.Engh, and D.Bossemeyer (2002).
Structural aspects of protein kinase control-role of conformational flexibility.
  Pharmacol Ther, 93, 99.  
12169624 R.M.Biondi, D.Komander, C.C.Thomas, J.M.Lizcano, M.Deak, D.R.Alessi, and D.M.van Aalten (2002).
High resolution crystal structure of the human PDK1 catalytic domain defines the regulatory phosphopeptide docking site.
  EMBO J, 21, 4219-4228.
PDB code: 1h1w
10608920 C.García-Echeverría, P.Traxler, and D.B.Evans (2000).
ATP site-directed competitive and irreversible inhibitors of protein kinases.
  Med Res Rev, 20, 28-57.  
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 codes are shown on the right.

 

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