PDBsum entry 2ogq

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protein links
Transferase PDB id
Protein chain
211 a.a. *
Waters ×193
* Residue conservation analysis
PDB id:
Name: Transferase
Title: Molecular and structural basis of plk1 substrate recognition: implications in centrosomal localization
Structure: Serine/threonine-protein kinase plk1. Chain: a. Fragment: polo-box domain, residues 365-603. Synonym: polo-like kinase 1, plk-1, serine/threonine- protein kinase 13, stpk13. Engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Gene: plk1, plk. Expressed in: escherichia coli. Expression_system_taxid: 562.
1.95Å     R-factor:   0.162     R-free:   0.221
Authors: B.Garcia-Alvarez,G.De Carcer,S.Ibanez,E.Bragado-Nilsson, G.Montoya
Key ref:
B.García-Alvarez et al. (2007). Molecular and structural basis of polo-like kinase 1 substrate recognition: Implications in centrosomal localization. Proc Natl Acad Sci U S A, 104, 3107-3112. PubMed id: 17307877 DOI: 10.1073/pnas.0609131104
08-Jan-07     Release date:   13-Feb-07    
Go to PROCHECK summary

Protein chain
Pfam   ArchSchema ?
P53350  (PLK1_HUMAN) -  Serine/threonine-protein kinase PLK1
603 a.a.
211 a.a.
Protein chain
Pfam   ArchSchema ?
Q59GD0  (Q59GD0_HUMAN) -  Polo-like kinase variant (Fragment)
546 a.a.
211 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class: E.C.  - Polo kinase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: ATP + a protein = ADP + a phosphoprotein
+ protein
+ phosphoprotein
Molecule diagrams generated from .mol files obtained from the KEGG ftp site


DOI no: 10.1073/pnas.0609131104 Proc Natl Acad Sci U S A 104:3107-3112 (2007)
PubMed id: 17307877  
Molecular and structural basis of polo-like kinase 1 substrate recognition: Implications in centrosomal localization.
B.García-Alvarez, Cárcer, S.Ibañez, E.Bragado-Nilsson, G.Montoya.
Polo-like kinase (Plk1) is crucial for cell cycle progression through mitosis. Here we present the molecular and structural mechanisms that regulate the substrate recognition of Plk1 and influence its centrosomal localization and activity. Our work shows that Plk1 localization is controlled not only by the polo box domain (PBD); remarkably, the kinase domain is also involved in Plk1 targeting mechanism to the centrosome. The crystal structures of the PBD in complex with Cdc25C and Cdc25C-P target peptides reveal that Trp-414 is fundamental in their recognition regardless of its phosphorylation status. Binding measurements demonstrate that W414F mutation abolishes molecular recognition and diminishes centrosomal localization. Therefore, Plk1 centrosomal localization is not controlled by His-538 and Lys-540, the residues involved in phosphorylated target binding. The different conformations of the loop, which connects the polo boxes in the apo and the PBD-Cdc25C and PBD-Cdc25C-P complex structures, together with changes in the proline adjacent to the phosphothreonine in the target peptide, suggest a regulatory mechanism to detect binding of unphosphorylated or phosphorylated target substrates. Altogether, these data propose a model for the interaction between Plk1 and Cdc25C.
  Selected figure(s)  
Figure 3.
Fig. 3. PBD Cdc25C peptide complex crystal structures. (a) Surface representation of the PBD/Cdc25C and the PBD/Cdc25C-P crystal structures. The coloring scheme represents the contact area between the target peptide and the protein ranging from cyan (no contact) to magenta (strong contact). The peptide is depicted in yellow stick representation. (b) 2F[o]–F[c] A-weighted electron-density map contoured at 1 showing the residues and the solvent molecules involved in the binding of the Cdc25C-P peptide. A water-mediated interaction of the phosphate moiety with Arg-518 and Lys-556 from two different crystallographically related molecules can be observed.
Figure 5.
Fig. 5. Hypothetical model of Plk1 interaction with Cdc25C during the cell cycle.
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
  20625469 C.Liao, J.E.Park, J.K.Bang, M.C.Nicklaus, and K.S.Lee (2010).
Exploring Potential Binding Modes of Small Drug-like Molecules to the Polo-Box Domain of Human Polo-like Kinase 1.
  ACS Med Chem Lett, 1, 110-114.  
  20711360 D.J.Huggins, G.J.McKenzie, D.D.Robinson, A.J.Narváez, B.Hardwick, M.Roberts-Thomson, A.R.Venkitaraman, G.H.Grant, and M.C.Payne (2010).
Computational analysis of phosphopeptide binding to the polo-box domain of the mitotic kinase PLK1 using molecular dynamics simulation.
  PLoS Comput Biol, 6, 0.  
20148280 J.E.Park, N.K.Soung, Y.Johmura, Y.H.Kang, C.Liao, K.H.Lee, C.H.Park, M.C.Nicklaus, and K.S.Lee (2010).
Polo-box domain: a versatile mediator of polo-like kinase function.
  Cell Mol Life Sci, 67, 1957-1970.  
20671765 K.Strebhardt (2010).
Multifaceted polo-like kinases: drug targets and antitargets for cancer therapy.
  Nat Rev Drug Discov, 9, 643-660.  
21102634 S.M.Lens, E.E.Voest, and R.H.Medema (2010).
Shared and separate functions of polo-like kinases and aurora kinases in cancer.
  Nat Rev Cancer, 10, 825-841.  
19546225 D.Vitour, S.Dabo, M.Ahmadi Pour, M.Vilasco, P.O.Vidalain, Y.Jacob, M.Mezel-Lemoine, S.Paz, M.Arguello, R.Lin, F.Tangy, J.Hiscott, and E.F.Meurs (2009).
Polo-like kinase 1 (PLK1) regulates interferon (IFN) induction by MAVS.
  J Biol Chem, 284, 21797-21809.  
22477774 F.Gorrec (2009).
The MORPHEUS protein crystallization screen.
  J Appl Crystallogr, 42, 1035-1042.  
19307309 K.Kishi, M.A.van Vugt, K.Okamoto, Y.Hayashi, and M.B.Yaffe (2009).
Functional dynamics of Polo-like kinase 1 at the centrosome.
  Mol Cell Biol, 29, 3134-3150.  
19568282 S.Lapenna, and A.Giordano (2009).
Cell cycle kinases as therapeutic targets for cancer.
  Nat Rev Drug Discov, 8, 547-566.  
19305416 V.Archambault, and D.M.Glover (2009).
Polo-like kinases: conservation and divergence in their functions and regulation.
  Nat Rev Mol Cell Biol, 10, 265-275.  
19152411 W.S.Wang, M.S.Lee, C.E.Tseng, I.H.Liao, S.P.Huang, R.I.Lin, and C.Li (2009).
Interaction between human papillomavirus type 5 E2 and polo-like kinase 1.
  J Med Virol, 81, 536-544.  
18215321 K.S.Lee, D.Y.Oh, Y.H.Kang, and J.E.Park (2008).
Self-regulated mechanism of Plk1 localization to kinetochores: lessons from the Plk1-PBIP1 interaction.
  Cell Div, 3, 4.  
18250627 K.U.Wendt, M.S.Weiss, P.Cramer, and D.W.Heinz (2008).
Structures and diseases.
  Nat Struct Mol Biol, 15, 117-120.  
18417573 L.E.Ludlow, M.K.Lo, J.J.Rodriguez, P.A.Rota, and C.M.Horvath (2008).
Henipavirus V protein association with Polo-like kinase reveals functional overlap with STAT1 binding and interferon evasion.
  J Virol, 82, 6259-6271.  
18599640 P.Cimmperman, L.Baranauskiene, S.Jachimoviciūte, J.Jachno, J.Torresan, V.Michailoviene, J.Matuliene, J.Sereikaite, V.Bumelis, and D.Matulis (2008).
A quantitative model of thermal stabilization and destabilization of proteins by ligands.
  Biophys J, 95, 3222-3231.  
  18678933 R.A.Elling, R.V.Fucini, E.J.Hanan, K.J.Barr, J.Zhu, K.Paulvannan, W.Yang, and M.J.Romanowski (2008).
Structure of the Brachydanio rerio Polo-like kinase 1 (Plk1) catalytic domain in complex with an extended inhibitor targeting the adaptive pocket of the enzyme.
  Acta Crystallogr Sect F Struct Biol Cryst Commun, 64, 686-691.
PDB code: 3db6
18703838 R.A.Elling, R.V.Fucini, and M.J.Romanowski (2008).
Structures of the wild-type and activated catalytic domains of Brachydanio rerio Polo-like kinase 1 (Plk1): changes in the active-site conformation and interactions with ligands.
  Acta Crystallogr D Biol Crystallogr, 64, 909-918.
PDB codes: 3d5u 3d5v 3d5w 3d5x
18832073 V.Archambault, P.P.D'Avino, M.J.Deery, K.S.Lilley, and D.M.Glover (2008).
Sequestration of Polo kinase to microtubules by phosphopriming-independent binding to Map205 is relieved by phosphorylation at a CDK site in mitosis.
  Genes Dev, 22, 2707-2720.  
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.