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PDBsum entry 1l3r

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protein ligands metals Protein-protein interface(s) links
Transferase PDB id
1l3r
Jmol
Contents
Protein chains
341 a.a. *
20 a.a. *
Ligands
ADP-AF3
MPD
Metals
_MG ×2
Waters ×233
* Residue conservation analysis
PDB id:
1l3r
Name: Transferase
Title: Crystal structure of a transition state mimic of the catalytic subunit of camp-dependent protein kinase
Structure: Camp-dependent protein kinase, alpha-catalytic subunit. Chain: e. Synonym: pka c-alpha. Engineered: yes. Camp-dependent protein kinase inhibitor, muscle/brain form. Chain: i. Fragment: residues 5-24.
Source: Mus musculus. House mouse. Organism_taxid: 10090. Expressed in: escherichia coli. Expression_system_taxid: 562. Synthetic: yes. Other_details: the peptide was chemically synthesized. The sequence of the peptide is naturally found in mus musculus (mouse).
Biol. unit: Dimer (from PQS)
Resolution:
2.00Å     R-factor:   0.205     R-free:   0.232
Authors: Madhusudan,P.Akamine,N.-H.Xuong,S.S.Taylor
Key ref:
Madhusudan et al. (2002). Crystal structure of a transition state mimic of the catalytic subunit of cAMP-dependent protein kinase. Nat Struct Biol, 9, 273-277. PubMed id: 11896404 DOI: 10.1038/nsb780
Date:
28-Feb-02     Release date:   20-Mar-02    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
P05132  (KAPCA_MOUSE) -  cAMP-dependent protein kinase catalytic subunit alpha
Seq:
Struc:
351 a.a.
341 a.a.*
Protein chain
Pfam   ArchSchema ?
P63249  (IPKA_RAT) -  cAMP-dependent protein kinase inhibitor alpha
Seq:
Struc:
76 a.a.
20 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 7 residue positions (black crosses)

 Enzyme reactions 
   Enzyme class: Chain E: E.C.2.7.11.11  - cAMP-dependent protein kinase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: ATP + a protein = ADP + a phosphoprotein
ATP
+ protein
=
ADP
Bound ligand (Het Group name = ADP)
corresponds exactly
+ phosphoprotein
Molecule diagrams generated from .mol files obtained from the KEGG ftp site
 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     sperm midpiece   16 terms 
  Biological process     regulation of proteasomal protein catabolic process   18 terms 
  Biochemical function     nucleotide binding     13 terms  

 

 
    reference    
 
 
DOI no: 10.1038/nsb780 Nat Struct Biol 9:273-277 (2002)
PubMed id: 11896404  
 
 
Crystal structure of a transition state mimic of the catalytic subunit of cAMP-dependent protein kinase.
Madhusudan, P.Akamine, N.H.Xuong, S.S.Taylor.
 
  ABSTRACT  
 
To understand the molecular mechanism underlying phosphoryl transfer of cAMP-dependent protein kinase, the structure of the catalytic subunit in complex with ADP, aluminum fluoride, Mg2+ ions and a substrate peptide was determined at 2.0 A resolution. Aluminum fluoride was modeled as AlF3 in a planar geometry; it is positioned 2.3 A from both the donor oxygen of ADP and the hydroxyl group of the recipient Ser residue. In this configuration, the aluminum atom forms a trigonal bipyramidal coordination with the oxygen atoms of the donor and recipient groups at the apical positions. This arrangement suggests that aluminum fluoride mimics the transition state and provides the first direct structural evidence for the in-line mechanism of phosphoryl transfer in a protein kinase.
 
  Selected figure(s)  
 
Figure 1.
Figure 1. Overall view of the Mg[2]ADP -SP20 -AlF[3] complex of the catalytic subunit (cAPK) with the difference density at the position of AlF[3]. a, The disordered region of the catalytic subunit consisting of residues 5 -13 is indicated by dashes. SP20 and Mg2+ ions are displayed in yellow and red, respectively, and ADP and AlF[3] are shown in green. The Gly-rich loop is colored in magenta, and black spheres indicate the three phosphorylation sites observed in the structure. The MPD molecule is displayed in cyan. This figure was generated using MOLSCRIPT33. b, Stereo view of the annealed F[o] - F[c] omit map contoured at 6.0 . This figure was generated from BOBSCRIPT33, 34. Dashed lines indicate the aluminum (Al) coordination with the -phosphate of ADP and the hydroxyl group of Ser from the SP20.
Figure 3.
Figure 3. Schematic representation depicting the detailed interactions of aluminum fluoride with Mg[2]ADP, active site residues of the catalytic subunit, water molecules and the phosphorylation site Ser from SP20. Mg2+ ions and water molecules are indicated in large and small spheres, respectively. Residues displayed in ball-and-stick representation exhibit the exact conformation and relative orientation as observed in the crystal structure; however, they have been displaced with respect to one another for clarity.
 
  The above figures are reprinted by permission from Macmillan Publishers Ltd: Nat Struct Biol (2002, 9, 273-277) copyright 2002.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
21052604 M.Montenegro, M.Garcia-Viloca, J.M.Lluch, and A.González-Lafont (2011).
A QM/MM study of the phosphoryl transfer to the Kemptide substrate catalyzed by protein kinase A. The effect of the phosphorylation state of the protein on the mechanism.
  Phys Chem Chem Phys, 13, 530-539.  
20652880 S.Re, T.Imai, J.Jung, S.Ten-No, and Y.Sugita (2011).
Geometrically associative yet electronically dissociative character in the transition state of enzymatic reversible phosphorylation.
  J Comput Chem, 32, 260-270.  
20971646 S.S.Taylor, and A.P.Kornev (2011).
Protein kinases: evolution of dynamic regulatory proteins.
  Trends Biochem Sci, 36, 65-77.  
20729810 C.A.Boguth, P.Singh, C.C.Huang, and J.J.Tesmer (2010).
Molecular basis for activation of G protein-coupled receptor kinases.
  EMBO J, 29, 3249-3259.
PDB codes: 3nyn 3nyo
20077512 E.D.Scheeff, H.L.Axelrod, M.D.Miller, H.J.Chiu, A.M.Deacon, I.A.Wilson, and G.Manning (2010).
Genomics, evolution, and crystal structure of a new family of bacterial spore kinases.
  Proteins, 78, 1470-1482.
PDB code: 2q83
21105670 I.Buch, D.Fishelovitch, N.London, B.Raveh, H.J.Wolfson, and R.Nussinov (2010).
Allosteric regulation of glycogen synthase kinase 3β: a theoretical study.
  Biochemistry, 49, 10890-10901.  
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
20336692 M.Rabiller, M.Getlik, S.Klüter, A.Richters, S.Tückmantel, J.R.Simard, and D.Rauh (2010).
Proteus in the world of proteins: conformational changes in protein kinases.
  Arch Pharm (Weinheim), 343, 193-206.  
20563625 P.Gruszczyński, M.Obuchowski, and R.Kaźmierkiewicz (2010).
Phosphorylation and ATP-binding induced conformational changes in the PrkC, Ser/Thr kinase from B. subtilis.
  J Comput Aided Mol Des, 24, 733-747.  
19361221 A.G.Turjanski, G.Hummer, and J.S.Gutkind (2009).
How mitogen-activated protein kinases recognize and phosphorylate their targets: A QM/MM study.
  J Am Chem Soc, 131, 6141-6148.  
19364770 C.C.Huang, K.Yoshino-Koh, and J.J.Tesmer (2009).
A Surface of the Kinase Domain Critical for the Allosteric Activation of G Protein-coupled Receptor Kinases.
  J Biol Chem, 284, 17206-17215.  
19433564 D.H.Fong, and A.M.Berghuis (2009).
Structural basis of APH(3')-IIIa-mediated resistance to N1-substituted aminoglycoside antibiotics.
  Antimicrob Agents Chemother, 53, 3049-3055.
PDB codes: 3h8p 3tm0
19141289 E.D.Scheeff, J.Eswaran, G.Bunkoczi, S.Knapp, and G.Manning (2009).
Structure of the Pseudokinase VRK3 Reveals a Degraded Catalytic Site, a Highly Conserved Kinase Fold, and a Putative Regulatory Binding Site.
  Structure, 17, 128-138.
PDB codes: 2jii 2v62
19918057 J.Eswaran, D.Patnaik, P.Filippakopoulos, F.Wang, R.L.Stein, J.W.Murray, J.M.Higgins, and S.Knapp (2009).
Structure and functional characterization of the atypical human kinase haspin.
  Proc Natl Acad Sci U S A, 106, 20198-20203.
PDB codes: 2vuw 3dlz 3iq7
19122195 J.Yang, E.J.Kennedy, J.Wu, M.S.Deal, J.Pennypacker, G.Ghosh, and S.S.Taylor (2009).
Contribution of Non-catalytic Core Residues to Activity and Regulation in Protein Kinase A.
  J Biol Chem, 284, 6241-6248.
PDB code: 2qur
19063708 S.Naviglio, M.Caraglia, A.Abbruzzese, E.Chiosi, D.Di Gesto, M.Marra, M.Romano, A.Sorrentino, L.Sorvillo, A.Spina, and G.Illiano (2009).
Protein kinase A as a biological target in cancer therapy.
  Expert Opin Ther Targets, 13, 83-92.  
19914822 T.Alber (2009).
Signaling mechanisms of the Mycobacterium tuberculosis receptor Ser/Thr protein kinases.
  Curr Opin Struct Biol, 19, 650-657.  
19008858 C.Mieczkowski, A.T.Iavarone, and T.Alber (2008).
Auto-activation mechanism of the Mycobacterium tuberculosis PknB receptor Ser/Thr kinase.
  EMBO J, 27, 3186-3197.
PDB codes: 3f61 3f69
17971450 E.J.Kennedy, G.Ghosh, and L.Pillus (2008).
Identification of functionally distinct regions that mediate biological activity of the protein kinase a homolog Tpk2.
  J Biol Chem, 283, 1084-1093.  
18423189 N.Kannan, and S.S.Taylor (2008).
Rethinking pseudokinases.
  Cell, 133, 204-205.  
18339619 P.Singh, B.Wang, T.Maeda, K.Palczewski, and J.J.Tesmer (2008).
Structures of rhodopsin kinase in different ligand states reveal key elements involved in G protein-coupled receptor kinase activation.
  J Biol Chem, 283, 14053-14062.
PDB codes: 3c4w 3c4x 3c4y 3c4z 3c50 3c51
17996741 S.S.Taylor, C.Kim, C.Y.Cheng, S.H.Brown, J.Wu, and N.Kannan (2008).
Signaling through cAMP and cAMP-dependent protein kinase: diverse strategies for drug design.
  Biochim Biophys Acta, 1784, 16-26.  
17933849 F.S.Domingues, J.Rahnenführer, and T.Lengauer (2007).
Conformational analysis of alternative protein structures.
  Bioinformatics, 23, 3131-3138.  
17932298 J.Wu, S.H.Brown, S.von Daake, and S.S.Taylor (2007).
PKA type IIalpha holoenzyme reveals a combinatorial strategy for isoform diversity.
  Science, 318, 274-279.
PDB code: 2qvs
18008170 M.Montenegro, M.Garcia-Viloca, A.González-Lafont, and J.M.Lluch (2007).
Comparative study of the prereactive Protein Kinase A Michaelis complex with Kemptide substrate.
  J Comput Aided Mol Des, 21, 603-615.  
17197699 P.Rellos, F.J.Ivins, J.E.Baxter, A.Pike, T.J.Nott, D.M.Parkinson, S.Das, S.Howell, O.Fedorov, Q.Y.Shen, A.M.Fry, S.Knapp, and S.J.Smerdon (2007).
Structure and regulation of the human Nek2 centrosomal kinase.
  J Biol Chem, 282, 6833-6842.
PDB code: 2jav
17455908 Y.O.You, and W.A.van der Donk (2007).
Mechanistic investigations of the dehydration reaction of lacticin 481 synthetase using site-directed mutagenesis.
  Biochemistry, 46, 5991-6000.  
17652083 Z.X.Wang, and J.W.Wu (2007).
The complete pathway for ERK2-catalyzed reaction. Evidence for an iso random Bi Bi mechanism.
  J Biol Chem, 282, 27678-27684.  
16522793 Y.Cheng, Y.Zhang, and J.A.McCammon (2006).
How does activation loop phosphorylation modulate catalytic activity in the cAMP-dependent protein kinase: a theoretical study.
  Protein Sci, 15, 672-683.  
15837193 C.J.Squire, J.M.Dickson, I.Ivanovic, and E.N.Baker (2005).
Structure and inhibition of the human cell cycle checkpoint kinase, Wee1A kinase: an atypical tyrosine kinase with a key role in CDK1 regulation.
  Structure, 13, 541-550.
PDB code: 1x8b
16227439 G.Henkelman, M.X.LaBute, C.S.Tung, P.W.Fenimore, and B.H.McMahon (2005).
Conformational dependence of a protein kinase phosphate transfer reaction.
  Proc Natl Acad Sci U S A, 102, 15347-15351.  
14695281 A.N.Hoofnagle, J.W.Stoner, T.Lee, S.S.Eaton, and N.G.Ahn (2004).
Phosphorylation-dependent changes in structure and dynamics in ERK2 detected by SDSL and EPR.
  Biophys J, 86, 395-403.  
15136582 R.A.Ivey, Y.M.Zhang, K.G.Virga, K.Hevener, R.E.Lee, C.O.Rock, S.Jackowski, and H.W.Park (2004).
The structure of the pantothenate kinase.ADP.pantothenate ternary complex reveals the relationship between the binding sites for substrate, allosteric regulator, and antimetabolites.
  J Biol Chem, 279, 35622-35629.
PDB code: 1sq5
15481030 T.Langer, M.Vogtherr, B.Elshorst, M.Betz, U.Schieborr, K.Saxena, and H.Schwalbe (2004).
NMR backbone assignment of a protein kinase catalytic domain by a combination of several approaches: application to the catalytic subunit of cAMP-dependent protein kinase.
  Chembiochem, 5, 1508-1516.  
12548283 T.A.Young, B.Delagoutte, J.A.Endrizzi, A.M.Falick, and T.Alber (2003).
Structure of Mycobacterium tuberculosis PknB supports a universal activation mechanism for Ser/Thr protein kinases.
  Nat Struct Biol, 10, 168-174.
PDB code: 1mru
12044161 A.Cook, E.D.Lowe, E.D.Chrysina, V.T.Skamnaki, N.G.Oikonomakos, and L.N.Johnson (2002).
Structural studies on phospho-CDK2/cyclin A bound to nitrate, a transition state analogue: implications for the protein kinase mechanism.
  Biochemistry, 41, 7301-7311.
PDB code: 1gy3
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.