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protein metals Protein-protein interface(s) links
Transferase PDB id
1f5q
Jmol
Contents
Protein chains
296 a.a. *
247 a.a. *
Metals
_CL
Waters ×166
* Residue conservation analysis
PDB id:
1f5q
Name: Transferase
Title: Crystal structure of murine gamma herpesvirus cyclin complexed to human cyclin dependent kinase 2
Structure: Cyclin dependent kinase 2. Chain: a, c. Engineered: yes. Gamma herpesvirus cyclin. Chain: b, d. Engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Expressed in: spodoptera frugiperda. Expression_system_taxid: 7108. Expression_system_cell_line: sf9 insect cells. Murid herpesvirus 4. Murine herpesvirus 68. Organism_taxid: 33708.
Biol. unit: Dimer (from PQS)
Resolution:
2.50Å     R-factor:   0.234     R-free:   0.278
Authors: G.L.Card,P.Knowles,H.Laman,N.Jones,N.Q.Mcdonald
Key ref:
G.L.Card et al. (2000). Crystal structure of a gamma-herpesvirus cyclin-cdk complex. EMBO J, 19, 2877-2888. PubMed id: 10856233 DOI: 10.1093/emboj/19.12.2877
Date:
15-Jun-00     Release date:   27-Dec-00    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chains
Pfam   ArchSchema ?
P24941  (CDK2_HUMAN) -  Cyclin-dependent kinase 2
Seq:
Struc: 		298 a.a.
296 a.a.
Protein chains
Pfam   ArchSchema ?
P89883  (P89883_MHV68) -  72
Seq:
Struc: 		252 a.a.
247 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 1 residue position (black cross)

 Enzyme reactions 
   Enzyme class: Chains A, C: E.C.2.7.11.22  - Cyclin-dependent kinase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: ATP + a protein = ADP + a phosphoprotein
ATP
 + protein
 = ADP
 + phosphoprotein
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   15 terms 
  Biological process     regulation of gene silencing   31 terms 
  Biochemical function     nucleotide binding     12 terms  

 

 
    reference    
 
 
DOI no: 10.1093/emboj/19.12.2877 EMBO J 19:2877-2888 (2000)
PubMed id: 10856233  
 
 
Crystal structure of a gamma-herpesvirus cyclin-cdk complex.
G.L.Card, P.Knowles, H.Laman, N.Jones, N.Q.McDonald.
 
  ABSTRACT  
 
Several gamma-herpesviruses encode proteins related to the mammalian cyclins, regulatory subunits of cyclin-dependent kinases (cdks) essential for cell cycle progression. We report a 2.5 A crystal structure of a full-length oncogenic viral cyclin from gamma-herpesvirus 68 complexed with cdk2. The viral cyclin binds cdk2 with an orientation different from cyclin A and makes several novel interactions at the interface, yet it activates cdk2 by triggering conformational changes similar to cyclin A. Sequences within the viral cyclin N-terminus lock part of the cdk2 T-loop within the core of the complex. These sequences and others are conserved amongst the viral and cellular D-type cyclins, suggesting that this structure has wider implications for other cyclin-cdk complexes. The observed resistance of this viral cyclin-cdk complex to inhibition by the p27(KIP:) cdk inhibitor is explained by sequence and conformational variation in the cyclin rendering the p27(KIP:)-binding site on the cyclin subunit non-functional.
 
  Selected figure(s)  
 
Figure 2.
Figure 2 (A) Structure of the M-cyclin–cdk2 complex. Cdk2 is shown in blue except for the PSTAIRE region (residues 38–56) in red and the T-loop (residues 146–166) in yellow. M-cyclin is shown in gold. (B) An equivalent view following rotation by 90° about the horizontal axis. The T-loop forms two antiparallel -strands, which are sandwiched between the PSTAIRE helix and the N-terminal region of M-cyclin. This figure and Figure 3A were prepared using PREPI (S.Islam and M.J.Sternberg, unpublished). (C) Highly schematic view of the two cyclin–cdk interfaces illustrating key structural elements and selected interface residues. The left hand panel is M-cyclin–cdk2, the right hand panel is cyclin A–cdk2. Colours for the indicated secondary structures follow (A) and Figure 3A. 		Figure 4.
Figure 4 (A) Surface representation of M-cyclin (gold, left) and cyclin A (purple, right) bound to their respective cdk2 partners (cyan C[ ]worm). The cdk2 PSTAIRE region is shown in red and the T-loop in yellow for both complexes as in Figure 2. The green surface of M-cyclin and cyclin A indicates the hydrophobic patch, which packs against the PSTAIRE helix. The shift in position of M-cyclin relative to cyclin A can be seen as well as the different contacts to the PSTAIRE helix. (B) Close-up of the hydrophobic patch of M-cyclin–cdk2 and cyclin A–cdk2 revealing differences in their interface contacts. (C) Stereo view of a conserved cyclin–cdk2 interaction centred on the salt bridge between K104^M and E133^M (top view) equivalent to K266^A and E295^A (bottom view) as described in the text. Certain residues in this region are omitted for clarity.
 
  The above figures are reprinted from an Open Access publication published by Macmillan Publishers Ltd: EMBO J (2000, 19, 2877-2888) copyright 2000.  
  Figures were selected by the author.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
21219186 E.Barton, P.Mandal, and S.H.Speck (2011).
Pathogenesis and host control of gammaherpesviruses: lessons from the mouse.
  Annu Rev Immunol, 29, 351-397.  
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.  
20638646 S.H.Speck, and D.Ganem (2010).
Viral latency and its regulation: lessons from the gamma-herpesviruses.
  Cell Host Microbe, 8, 100-115.  
18827403 Z.Wang, Y.Xie, L.Zhang, H.Zhang, X.An, T.Wang, and A.Meng (2008).
Migratory localization of cyclin D2-Cdk4 complex suggests a spatial regulation of the G1-S transition.
  Cell Struct Funct, 33, 171-183.  
17594507 J.L.Chung, W.Wang, and P.E.Bourne (2007).
High-throughput identification of interacting protein-protein binding sites.
  BMC Bioinformatics, 8, 223.  
17169370 K.Baek, R.S.Brown, G.Birrane, and J.A.Ladias (2007).
Crystal structure of human cyclin K, a positive regulator of cyclin-dependent kinase 9.
  J Mol Biol, 366, 563-573.
PDB code: 2i53
16584130 J.Sridhar, N.Akula, and N.Pattabiraman (2006).
Selectivity and potency of cyclin-dependent kinase inhibitors.
  AAPS J, 8, E204-E221.  
17005668 J.W.Upton, and S.H.Speck (2006).
Evidence for CDK-dependent and CDK-independent functions of the murine gammaherpesvirus 68 v-cyclin.
  J Virol, 80, 11946-11959.  
15906321 A.J.Bordner, and R.Abagyan (2005).
Statistical analysis and prediction of protein-protein interfaces.
  Proteins, 60, 353-366.  
14700606 C.Swanton (2004).
Cell-cycle targeted therapies.
  Lancet Oncol, 5, 27-36.  
12794189 L.A.Dourmishev, A.L.Dourmishev, D.Palmeri, R.A.Schwartz, and D.M.Lukac (2003).
Molecular genetics of Kaposi's sarcoma-associated herpesvirus (human herpesvirus-8) epidemiology and pathogenesis.
  Microbiol Mol Biol Rev, 67, 175.  
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.  
11828325 U.Schulze-Gahmen, and S.H.Kim (2002).
Structural basis for CDK6 activation by a virus-encoded cyclin.
  Nat Struct Biol, 9, 177-181.
PDB code: 1jow
11422537 C.Swanton, and N.Jones (2001).
Strategies in subversion: de-regulation of the mammalian cell cycle by viral gene products.
  Int J Exp Pathol, 82, 3.  
11583627 C.Tarricone, R.Dhavan, J.Peng, L.B.Areces, L.H.Tsai, and A.Musacchio (2001).
Structure and regulation of the CDK5-p25(nck5a) complex.
  Mol Cell, 8, 657-669.
PDB code: 1h4l
11124804 P.D.Jeffrey, L.Tong, and N.P.Pavletich (2000).
Structural basis of inhibition of CDK-cyclin complexes by INK4 inhibitors.
  Genes Dev, 14, 3115-3125.
PDB code: 1g3n
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.