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PDBsum entry 1fq1

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protein ligands metals Protein-protein interface(s) links
Hydrolase/transferase PDB id
1fq1
Jmol
Contents
Protein chains
183 a.a. *
296 a.a. *
Ligands
ATP
Metals
_MG
* Residue conservation analysis
PDB id:
1fq1
Name: Hydrolase/transferase
Title: Crystal structure of kinase associated phosphatase (kap) in complex with phospho-cdk2
Structure: Cyclin-dependent kinase inhibitor 3. Chain: a. Engineered: yes. Mutation: yes. Cell division protein kinase 2. Chain: b. Engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Expressed in: escherichia coli. Expression_system_taxid: 562. Other_details: homo sapiens. Other_details: homo sapiens
Biol. unit: Dimer (from PQS)
Resolution:
3.00Å     R-factor:   0.235     R-free:   0.313
Authors: H.Song,N.Hanlon,N.R.Brown,M.E.M.Noble,L.N.Johnson,D.Barford
Key ref:
H.Song et al. (2001). Phosphoprotein-protein interactions revealed by the crystal structure of kinase-associated phosphatase in complex with phosphoCDK2. Mol Cell, 7, 615-626. PubMed id: 11463386 DOI: 10.1016/S1097-2765(01)00208-8
Date:
01-Sep-00     Release date:   09-May-01    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
Q16667  (CDKN3_HUMAN) -  Cyclin-dependent kinase inhibitor 3
Seq:
Struc:
212 a.a.
183 a.a.*
Protein chain
Pfam   ArchSchema ?
P24941  (CDK2_HUMAN) -  Cyclin-dependent kinase 2
Seq:
Struc:
298 a.a.
296 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 2 residue positions (black crosses)

 Enzyme reactions 
   Enzyme class 1: Chain A: E.C.3.1.3.16  - Protein-serine/threonine phosphatase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: [a protein]-serine/threonine phosphate + H2O = [a protein]- serine/threonine + phosphate
[a protein]-serine/threonine phosphate
+ H(2)O
= [a protein]- serine/threonine
+ phosphate
   Enzyme class 2: Chain A: E.C.3.1.3.48  - Protein-tyrosine-phosphatase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: Protein tyrosine phosphate + H2O = protein tyrosine + phosphate
Protein tyrosine phosphate
+ H(2)O
= protein tyrosine
+ phosphate
   Enzyme class 3: Chain B: E.C.2.7.11.22  - Cyclin-dependent kinase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: ATP + a protein = ADP + a phosphoprotein
ATP
Bound ligand (Het Group name = ATP)
corresponds exactly
+ protein
= ADP
+ phosphoprotein
Note, where more than one E.C. class is given (as above), each may correspond to a different protein domain or, in the case of polyprotein precursors, to a different mature protein.
Molecule diagrams generated from .mol files obtained from the KEGG ftp site
 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     cyclin-dependent protein kinase holoenzyme complex   16 terms 
  Biological process     peptidyl-tyrosine dephosphorylation   32 terms 
  Biochemical function     protein binding     18 terms  

 

 
    reference    
 
 
DOI no: 10.1016/S1097-2765(01)00208-8 Mol Cell 7:615-626 (2001)
PubMed id: 11463386  
 
 
Phosphoprotein-protein interactions revealed by the crystal structure of kinase-associated phosphatase in complex with phosphoCDK2.
H.Song, N.Hanlon, N.R.Brown, M.E.Noble, L.N.Johnson, D.Barford.
 
  ABSTRACT  
 
The CDK-interacting protein phosphatase KAP dephosphorylates phosphoThr-160 (pThr-160) of the CDK2 activation segment, the site of regulatory phosphorylation that is essential for kinase activity. Here we describe the crystal structure of KAP in association with pThr-160-CDK2, representing an example of a protein phosphatase in complex with its intact protein substrate. The major protein interface between the two molecules is formed by the C-terminal lobe of CDK2 and the C-terminal helix of KAP, regions remote from the kinase-activation segment and the KAP catalytic site. The kinase-activation segment interacts with the catalytic site of KAP almost entirely via the phosphate group of pThr-160. This interaction requires that the activation segment is unfolded and drawn away from the kinase molecule, inducing a conformation of CDK2 similar to the activated state observed in the CDK2/cyclin A complex.
 
  Selected figure(s)  
 
Figure 1.
Figure 1. Structures of KAP and PTP1B(A) Stereo view showing a 2F[o]-F[c] electron density omit map contoured at 1σ in the vicinity of the catalytic Cys residue (Cys-140) of wild-type KAP revealing the formation of a disulphide bond to Cys-79.(B) Ribbon diagram comparing KAPt with PTP1B. The PTP loop of both molecules is shown in yellow, the acid/base loop (WPD loop) in red, and the Q loop in white. The pTyr recognition segment of PTP1B is in green. A sulfate ion and pTyr residue are shown at the catalytic sites of KAPt and PTP1B, respectively. Figures were created using AESOP (M. E. M. N., unpublished data), BOBSCRIPT (Esnouf, 1997), and Raster3D (Merit and Murphy, 1994)
Figure 4.
Figure 4. The Conformation of pCDK2 in the pCDK2/KAPt Complex Represents the Activated ConformationA structural comparison of CDK2 as the nonphosphorylated monomer in the pCDK2/cyclin A complex and in the pCDK2/KAPt complex. Except for differences in the conformation of the activation segment residues 152–165, the conformation of CDK2 in the pCDK2/cyclin A binary complex is most similar to the pCDK2/KAPt structure. The N- and C-terminal lobes of CDK2 are colored white and gold, respectively, and the C helix is shown in magenta. The activation segment is green, except for residues 153–164 that are disordered in monomeric pCDK2 and are shown in red
 
  The above figures are reprinted by permission from Cell Press: Mol Cell (2001, 7, 615-626) copyright 2001.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
19566963 B.T.Tobe, A.A.Kitazono, J.S.Garcia, R.A.Gerber, B.J.Bevis, J.S.Choy, D.Chasman, and S.J.Kron (2009).
Morphogenesis signaling components influence cell cycle regulation by cyclin dependent kinase.
  Cell Div, 4, 12.  
19501598 J.J.Perry, R.M.Harris, D.Moiani, A.J.Olson, and J.A.Tainer (2009).
p38alpha MAP kinase C-terminal domain binding pocket characterized by crystallographic and computational analyses.
  J Mol Biol, 391, 1.
PDB code: 3hvc
20005845 K.Fukuda, S.Gupta, K.Chen, C.Wu, and J.Qin (2009).
The pseudoactive site of ILK is essential for its binding to alpha-Parvin and localization to focal adhesions.
  Mol Cell, 36, 819-830.
PDB codes: 3kmu 3kmw
19424502 M.C.Balasu, L.N.Spiridon, S.Miron, C.T.Craescu, A.J.Scheidig, A.J.Petrescu, and S.E.Szedlacsek (2009).
Interface analysis of the complex between ERK2 and PTP-SL.
  PLoS ONE, 4, e5432.  
19530248 R.A.Romano, N.Kannan, A.P.Kornev, C.J.Allison, and S.S.Taylor (2009).
A chimeric mechanism for polyvalent trans-phosphorylation of PKA by PDK1.
  Protein Sci, 18, 1486-1497.  
19306398 Y.Li, and A.G.Palmer (2009).
Domain swapping in the kinase superfamily: OSR1 joins the mix.
  Protein Sci, 18, 678-681.  
18787129 A.P.Kornev, S.S.Taylor, and L.F.Ten Eyck (2008).
A helix scaffold for the assembly of active protein kinases.
  Proc Natl Acad Sci U S A, 105, 14377-14382.  
18433060 D.J.Aceti, E.Bitto, A.F.Yakunin, M.Proudfoot, C.A.Bingman, R.O.Frederick, H.K.Sreenath, F.C.Vojtik, R.L.Wrobel, B.G.Fox, J.L.Markley, and G.N.Phillips (2008).
Structural and functional characterization of a novel phosphatase from the Arabidopsis thaliana gene locus At1g05000.
  Proteins, 73, 241-253.
PDB code: 1xri
18946488 D.Komander, R.Garg, P.T.Wan, A.J.Ridley, and D.Barford (2008).
Mechanism of multi-site phosphorylation from a ROCK-I:RhoE complex structure.
  EMBO J, 27, 3175-3185.
PDB code: 2v55
18298792 R.Pulido, and R.Hooft van Huijsduijnen (2008).
Protein tyrosine phosphatases: dual-specificity phosphatases in health and disease.
  FEBS J, 275, 848-866.  
17078075 D.G.Jeong, Y.H.Cho, T.S.Yoon, J.H.Kim, S.E.Ryu, and S.J.Kim (2007).
Crystal structure of the catalytic domain of human DUSP5, a dual specificity MAP kinase protein phosphatase.
  Proteins, 66, 253-258.
PDB code: 2g6z
17325030 G.Guillemain, E.Ma, S.Mauger, S.Miron, R.Thai, R.Guérois, F.Ochsenbein, and M.C.Marsolier-Kergoat (2007).
Mechanisms of checkpoint kinase Rad53 inactivation after a double-strand break in Saccharomyces cerevisiae.
  Mol Cell Biol, 27, 3378-3389.  
17373709 G.Lolli, and L.N.Johnson (2007).
Recognition of Cdk2 by Cdk7.
  Proteins, 67, 1048-1059.
PDB code: 2hic
17173287 H.M.Chu, and A.H.Wang (2007).
Enzyme-substrate interactions revealed by the crystal structures of the archaeal Sulfolobus PTP-fold phosphatase and its phosphopeptide complexes.
  Proteins, 66, 996.
PDB codes: 2dxp 2i6i 2i6j 2i6m 2i6o 2i6p
17286863 J.Gu, and P.E.Bourne (2007).
Identifying allosteric fluctuation transitions between different protein conformational states as applied to Cyclin Dependent Kinase 2.
  BMC Bioinformatics, 8, 45.  
17287826 J.Rudolph (2007).
Inhibiting transient protein-protein interactions: lessons from the Cdc25 protein tyrosine phosphatases.
  Nat Rev Cancer, 7, 202-211.  
17400920 X.Tao, and L.Tong (2007).
Crystal structure of the MAP kinase binding domain and the catalytic domain of human MKP5.
  Protein Sci, 16, 880-886.
PDB codes: 2ouc 2oud
16628247 E.S.Groban, A.Narayanan, and M.P.Jacobson (2006).
Conformational changes in protein loops and helices induced by post-translational phosphorylation.
  PLoS Comput Biol, 2, e32.  
16584130 J.Sridhar, N.Akula, and N.Pattabiraman (2006).
Selectivity and potency of cyclin-dependent kinase inhibitors.
  AAPS J, 8, E204-E221.  
16707497 K.Y.Cheng, M.E.Noble, V.Skamnaki, N.R.Brown, E.D.Lowe, L.Kontogiannis, K.Shen, P.A.Cole, G.Siligardi, and L.N.Johnson (2006).
The role of the phospho-CDK2/cyclin A recruitment site in substrate recognition.
  J Biol Chem, 281, 23167-23179.
PDB codes: 2cch 2cci
16790931 R.C.Hillig, and L.Renault (2006).
Detecting and overcoming hemihedral twinning during the MIR structure determination of Rna1p.
  Acta Crystallogr D Biol Crystallogr, 62, 750-765.
PDB code: 2ca6
15713658 A.Changela, A.Martins, S.Shuman, and A.Mondragón (2005).
Crystal structure of baculovirus RNA triphosphatase complexed with phosphate.
  J Biol Chem, 280, 17848-17856.
PDB code: 1yn9
16191191 A.Cheng, S.Gerry, P.Kaldis, and M.J.Solomon (2005).
Biochemical characterization of Cdk2-Speedy/Ringo A2.
  BMC Biochem, 6, 19.  
15890001 A.Salmeen, and D.Barford (2005).
Functions and mechanisms of redox regulation of cysteine-based phosphatases.
  Antioxid Redox Signal, 7, 560-577.  
15515182 Anamika, N.Srinivasan, and A.Krupa (2005).
A genomic perspective of protein kinases in Plasmodium falciparum.
  Proteins, 58, 180-189.  
15692043 C.Kim, N.H.Xuong, and S.S.Taylor (2005).
Crystal structure of a complex between the catalytic and regulatory (RIalpha) subunits of PKA.
  Science, 307, 690-696.
PDB codes: 1u7e 3fhi
16354836 D.Tobi, and I.Bahar (2005).
Structural changes involved in protein binding correlate with intrinsic motions of proteins in the unbound state.
  Proc Natl Acad Sci U S A, 102, 18908-18913.  
15611135 F.Villa, M.Deak, G.B.Bloomberg, D.R.Alessi, and D.M.van Aalten (2005).
Crystal structure of the PTPL1/FAP-1 human tyrosine phosphatase mutated in colorectal cancer: evidence for a second phosphotyrosine substrate recognition pocket.
  J Biol Chem, 280, 8180-8187.
PDB code: 1wch
15890022 J.Rudolph (2005).
Redox regulation of the Cdc25 phosphatases.
  Antioxid Redox Signal, 7, 761-767.  
15671017 M.Chinami, Y.Yano, X.Yang, S.Salahuddin, K.Moriyama, M.Shiroishi, H.Turner, T.Shirakawa, and C.N.Adra (2005).
Binding of HTm4 to cyclin-dependent kinase (Cdk)-associated phosphatase (KAP).Cdk2.cyclin A complex enhances the phosphatase activity of KAP, dissociates cyclin A, and facilitates KAP dephosphorylation of Cdk2.
  J Biol Chem, 280, 17235-17242.  
15660127 R.Honda, E.D.Lowe, E.Dubinina, V.Skamnaki, A.Cook, N.R.Brown, and L.N.Johnson (2005).
The structure of cyclin E1/CDK2: implications for CDK2 activation and CDK2-independent roles.
  EMBO J, 24, 452-463.
PDB code: 1w98
16179248 S.S.Taylor, N.M.Haste, and G.Ghosh (2005).
PKR and eIF2alpha: integration of kinase dimerization, activation, and substrate docking.
  Cell, 122, 823-825.  
16170801 T.S.Yoon, D.G.Jeong, J.H.Kim, Y.H.Cho, J.H.Son, J.W.Lee, S.E.Ryu, and S.J.Kim (2005).
Crystal structure of the catalytic domain of human VHY, a dual-specificity protein phosphatase.
  Proteins, 61, 694-697.
PDB code: 1yz4
14704153 G.Kozlov, J.Cheng, E.Ziomek, D.Banville, K.Gehring, and I.Ekiel (2004).
Structural insights into molecular function of the metastasis-associated phosphatase PRL-3.
  J Biol Chem, 279, 11882-11889.
PDB code: 1r6h
14625311 J.Felberg, D.C.Lefebvre, M.Lam, Y.Wang, D.H.Ng, D.Birkenhead, J.L.Cross, and P.Johnson (2004).
Subdomain X of the kinase domain of Lck binds CD45 and facilitates dephosphorylation.
  J Biol Chem, 279, 3455-3462.  
15534213 J.Sohn, K.Kristjánsdóttir, A.Safi, B.Parker, B.Kiburz, and J.Rudolph (2004).
Remote hot spots mediate protein substrate recognition for the Cdc25 phosphatase.
  Proc Natl Acad Sci U S A, 101, 16437-16441.  
15128740 W.Q.Wang, J.Bembenek, K.R.Gee, H.Yu, H.Charbonneau, and Z.Y.Zhang (2004).
Kinetic and mechanistic studies of a cell cycle protein phosphatase Cdc14.
  J Biol Chem, 279, 30459-30468.  
12853468 C.H.Gray, V.M.Good, N.K.Tonks, and D.Barford (2003).
The structure of the cell cycle protein Cdc14 reveals a proline-directed protein phosphatase.
  EMBO J, 22, 3524-3535.
PDB codes: 1ohc 1ohd 1ohe
14506247 F.L.Chou, J.M.Hill, J.C.Hsieh, J.Pouyssegur, A.Brunet, A.Glading, F.Uberall, J.W.Ramos, M.H.Werner, and M.H.Ginsberg (2003).
PEA-15 binding to ERK1/2 MAPKs is required for its modulation of integrin activation.
  J Biol Chem, 278, 52587-52597.  
12554650 R.Dajani, E.Fraser, S.M.Roe, M.Yeo, V.M.Good, V.Thompson, T.C.Dale, and L.H.Pearl (2003).
Structural basis for recruitment of glycogen synthase kinase 3beta to the axin-APC scaffold complex.
  EMBO J, 22, 494-501.
PDB code: 1o9u
12359726 A.A.Kitazono, and S.J.Kron (2002).
An essential function of yeast cyclin-dependent kinase Cdc28 maintains chromosome stability.
  J Biol Chem, 277, 48627-48634.  
11847098 C.Blanchetot, L.G.Tertoolen, and J.den Hertog (2002).
Regulation of receptor protein-tyrosine phosphatase alpha by oxidative stress.
  EMBO J, 21, 493-503.  
12065620 F.Mukai, K.Ishiguro, Y.Sano, and S.C.Fujita (2002).
Alternative splicing isoform of tau protein kinase I/glycogen synthase kinase 3beta.
  J Neurochem, 81, 1073-1083.  
12191604 L.N.Johnson, E.De Moliner, N.R.Brown, H.Song, D.Barford, J.A.Endicott, and M.E.Noble (2002).
Structural studies with inhibitors of the cell cycle regulatory kinase cyclin-dependent protein kinase 2.
  Pharmacol Ther, 93, 113-124.  
11859026 M.Bollen, and M.Beullens (2002).
Signaling by protein phosphatases in the nucleus.
  Trends Cell Biol, 12, 138-145.  
11959850 M.C.Morris, C.Gondeau, J.A.Tainer, and G.Divita (2002).
Kinetic mechanism of activation of the Cdk2/cyclin A complex. Key role of the C-lobe of the Cdk.
  J Biol Chem, 277, 23847-23853.  
12209150 T.O.Johnson, J.Ermolieff, and M.R.Jirousek (2002).
Protein tyrosine phosphatase 1B inhibitors for diabetes.
  Nat Rev Drug Discov, 1, 696-709.  
11807171 Z.Y.Zhang (2002).
Protein tyrosine phosphatases: structure and function, substrate specificity, and inhibitor development.
  Annu Rev Pharmacol Toxicol, 42, 209-234.  
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.