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PDBsum entry 1dkt
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Cell division PDB id
1dkt

 

 

 

 

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Contents
Protein chains
72 a.a. *
Ligands
V7O
Waters ×62
* Residue conservation analysis
PDB id:
1dkt
Name: Cell division
Title: Ckshs1: human cyclin dependent kinase subunit, type 1 complex with metavanadate
Structure: Cyclin dependent kinase subunit, type 1. Chain: a, b. Synonym: ckshs1. Engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Expressed in: escherichia coli. Expression_system_taxid: 562.
Resolution:
2.90Å     R-factor:   0.195     R-free:   0.258
Authors: Y.Bourne,A.S.Arvai,J.A.Tainer
Key ref: A.S.Arvai et al. (1995). Crystal structure of the human cell cycle protein CksHs1: single domain fold with similarity to kinase N-lobe domain. J Mol Biol, 249, 835-842. PubMed id: 7791211
Date:
22-Nov-95     Release date:   08-Mar-96    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chains
Pfam   ArchSchema ?
P61024  (CKS1_HUMAN) -  Cyclin-dependent kinases regulatory subunit 1 from Homo sapiens
Seq:
Struc: 		79 a.a.
72 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class: E.C.?
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]

 

 
J Mol Biol 249:835-842 (1995)
PubMed id: 7791211  
 
 
Crystal structure of the human cell cycle protein CksHs1: single domain fold with similarity to kinase N-lobe domain.
A.S.Arvai, Y.Bourne, M.J.Hickey, J.A.Tainer.
 
  ABSTRACT  
 
The structure of the human CksHs1 homolog of the yeast cell-cycle regulatory proteins suc1 and CKS1, which bind to the catalytic subunit of the cyclin-dependent kinases (Cdks) and are essential for yeast cell-cycle progression in vivo, has been determined at 2.9 A resolution. The CksHs1 single polypeptide domain fold, which consists of a four-stranded beta-sheet flanked by two alpha-helices, is dramatically different from the subunit conformation and assembly of the homologous CksHs2, but strikingly similar to the Cdk N-lobe domain fold. The CksHs1 structure identifies sequence-conserved residues Glu61 to His65 as a novel beta-hinge region that folds back to form a beta-hairpin with CksHs1 subunit, whereas this hinge is unfolded to form an extended beta-strand exchange between two CksHs2 subunits. Phosphate and the phosphate analog metavanadate bind CksHs1 in a shallow pocket and interact with five conserved residues (Lys11, Arg20, Ser51, Trp54 and Arg71) suggesting a specific Cks recognition site for a phosphorylated Cdk residue. The dramatic changes to the Cks fold, assembly and exposed conserved surface brought about by switching between the bent and extended hinge conformations are potentially important for the functions of this Cks homolog and could explain conflicting activities inferred from different types of genetic experiments.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
21993622 M.Kõivomägi, E.Valk, R.Venta, A.Iofik, M.Lepiku, E.R.Balog, S.M.Rubin, D.O.Morgan, and M.Loog (2011).
Cascades of multisite phosphorylation control Sic1 destruction at the onset of S phase.
  Nature, 480, 128-131.  
19228269 A.Krishnan, S.A.Nair, and M.R.Pillai (2010).
Loss of cks1 homeostasis deregulates cell division cycle.
  J Cell Mol Med, 14, 154-164.  
19786724 M.Radulovic, E.Crane, M.Crawford, J.Godovac-Zimmermann, and V.P.Yu (2010).
CKS proteins protect mitochondrial genome integrity by interacting with mitochondrial single-stranded DNA-binding protein.
  Mol Cell Proteomics, 9, 145-152.  
20516216 R.Holic, A.Kukalev, S.Lane, E.J.Andress, I.Lau, C.W.Yu, M.J.Edelmann, B.M.Kessler, and V.P.Yu (2010).
Cks1 activates transcription by binding to the ubiquitylated proteasome.
  Mol Cell Biol, 30, 3894-3901.  
17892493 G.Lippens, I.Landrieu, and C.Smet (2007).
Molecular mechanisms of the phospho-dependent prolyl cis/trans isomerase Pin1.
  FEBS J, 274, 5211-5222.  
17585314 J.A.Ubersax, and J.E.Ferrell (2007).
Mechanisms of specificity in protein phosphorylation.
  Nat Rev Mol Cell Biol, 8, 530-541.  
18047746 T.Cardozo, and M.Pagano (2007).
Wrenches in the works: drug discovery targeting the SCF ubiquitin ligase and APC/C complexes.
  BMC Biochem, 8, S9.  
16675442 R.Bader, M.A.Seeliger, S.E.Kelly, L.L.Ilag, F.Meersman, A.Limones, B.F.Luisi, C.M.Dobson, and L.S.Itzhaki (2006).
Folding and fibril formation of the cell cycle protein Cks1.
  J Biol Chem, 281, 18816-18824.  
16209941 B.Hao, N.Zheng, B.A.Schulman, G.Wu, J.J.Miller, M.Pagano, and N.P.Pavletich (2005).
Structural basis of the Cks1-dependent recognition of p27(Kip1) by the SCF(Skp2) ubiquitin ligase.
  Mol Cell, 20, 9.
PDB codes: 2ass 2ast
15772084 M.A.Seeliger, M.Spichty, S.E.Kelly, M.Bycroft, S.M.Freund, M.Karplus, and L.S.Itzhaki (2005).
Role of conformational heterogeneity in domain swapping and adapter function of the Cks proteins.
  J Biol Chem, 280, 30448-30459.  
15629725 V.P.Yu, C.Baskerville, B.Grünenfelder, and S.I.Reed (2005).
A kinase-independent function of Cks1 and Cdk1 in regulation of transcription.
  Mol Cell, 17, 145-151.  
12623012 F.Rousseau, J.W.Schymkowitz, and L.S.Itzhaki (2003).
The unfolding story of three-dimensional domain swapping.
  Structure, 11, 243-251.  
12897769 M.A.Seeliger, S.E.Breward, A.Friedler, O.Schon, and L.S.Itzhaki (2003).
Cooperative organization in a macromolecular complex.
  Nat Struct Biol, 10, 718-724.  
11812792 B.Odaert, I.Landrieu, K.Dijkstra, G.Schuurman-Wolters, P.Casteels, J.M.Wieruszeski, D.Inze, R.Scheek, and G.Lippens (2002).
Solution NMR study of the monomeric form of p13suc1 protein sheds light on the hinge region determining the affinity for a phosphorylated substrate.
  J Biol Chem, 277, 12375-12381.  
12140288 D.Sitry, M.A.Seeliger, T.K.Ko, D.Ganoth, S.E.Breward, L.S.Itzhaki, M.Pagano, and A.Hershko (2002).
Three different binding sites of Cks1 are required for p27-ubiquitin ligation.
  J Biol Chem, 277, 42233-42240.  
11839489 M.E.Newcomer (2002).
Protein folding and three-dimensional domain swapping: a strained relationship?
  Curr Opin Struct Biol, 12, 48-53.  
12021428 Y.Liu, and D.Eisenberg (2002).
3D domain swapping: as domains continue to swap.
  Protein Sci, 11, 1285-1299.  
11319029 L.De Veylder, G.T.Beemster, T.Beeckman, and D.Inzé (2001).
CKS1At overexpression in Arabidopsis thaliana inhibits growth by reducing meristem size and inhibiting cell-cycle progression.
  Plant J, 25, 617-626.  
10673427 D.O.Alonso, E.Alm, and V.Daggett (2000).
Characterization of the unfolding pathway of the cell-cycle protein p13suc1 by molecular dynamics simulations: implications for domain swapping.
  Structure, 8, 101-110.  
10673431 J.W.Schymkowitz, F.Rousseau, L.R.Irvine, and L.S.Itzhaki (2000).
The folding pathway of the cell-cycle regulatory protein p13suc1: clues for the mechanism of domain swapping.
  Structure, 8, 89.  
10997903 Y.Bourne, M.H.Watson, A.S.Arvai, S.L.Bernstein, S.I.Reed, and J.A.Tainer (2000).
Crystal structure and mutational analysis of the Saccharomyces cerevisiae cell cycle regulatory protein Cks1: implications for domain swapping, anion binding and protein interactions.
  Structure, 8, 841-850.
PDB code: 1qb3
10360827 I.Urbanowicz-Kachnowicz, N.Baghdassarian, C.Nakache, D.Gracia, Y.Mekki, P.A.Bryon, and M.Ffrench (1999).
ckshs expression is linked to cell proliferation in normal and malignant human lymphoid cells.
  Int J Cancer, 82, 98.  
10607671 J.A.Endicott, M.E.Noble, and J.A.Tucker (1999).
Cyclin-dependent kinases: inhibition and substrate recognition.
  Curr Opin Struct Biol, 9, 738-744.  
  9716407 D.Patra, and W.G.Dunphy (1998).
Xe-p9, a Xenopus Suc1/Cks protein, is essential for the Cdc2-dependent phosphorylation of the anaphase- promoting complex at mitosis.
  Genes Dev, 12, 2549-2559.  
  9632748 E.A.Egan, and M.J.Solomon (1998).
Cyclin-stimulated binding of Cks proteins to cyclin-dependent kinases.
  Mol Cell Biol, 18, 3659-3667.  
9760264 M.C.Morris, F.Heitz, and G.Divita (1998).
Kinetics of dimerization and interactions of p13suc1 with cyclin-dependent kinases.
  Biochemistry, 37, 14257-14266.  
  9841670 M.D.Mendenhall, and A.E.Hodge (1998).
Regulation of Cdc28 cyclin-dependent protein kinase activity during the cell cycle of the yeast Saccharomyces cerevisiae.
  Microbiol Mol Biol Rev, 62, 1191-1243.  
8611549 C.Birck, P.Vachette, M.Welch, P.Swarén, and J.P.Samama (1996).
Is the function of the cdc2 kinase subunit proteins tuned by their propensities to oligomerize? Conformational states in solution of the cdc2 kinase partners p13suc1 and p9cksphy.
  Biochemistry, 35, 5577-5585.  
8939669 D.O.Morgan (1996).
The dynamics of cyclin dependent kinase structure.
  Curr Opin Cell Biol, 8, 767-772.  
8939596 J.Pines (1996).
Cell cycle: reaching for a role for the Cks proteins.
  Curr Biol, 6, 1399-1402.  
8805536 N.Khazanovich, K.Bateman, M.Chernaia, M.Michalak, and M.James (1996).
Crystal structure of the yeast cell-cycle control protein, p13suc1, in a strand-exchanged dimer.
  Structure, 4, 299-309.
PDB code: 1puc
8601310 Y.Bourne, M.H.Watson, M.J.Hickey, W.Holmes, W.Rocque, S.I.Reed, and J.A.Tainer (1996).
Crystal structure and mutational analysis of the human CDK2 kinase complex with cell cycle-regulatory protein CksHs1.
  Cell, 84, 863-874.
PDB code: 1buh
  8580836 M.J.Bennett, M.P.Schlunegger, and D.Eisenberg (1995).
3D domain swapping: a mechanism for oligomer assembly.
  Protein Sci, 4, 2455-2468.  
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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