PDBsum entry 2ogq

Transferase

PDB id: 2ogq

Contents

Protein chain

211 a.a. *

Waters ×193

* Residue conservation analysis

PDB id:

2ogq

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.

Resolution:

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

Date:

08-Jan-07 Release date: 13-Feb-07

Protein chain

P53350  (PLK1_HUMAN) -  Serine/threonine-protein kinase PLK1 from Homo sapiens

Seq: 603 a.a.

Struc: 211 a.a.

Enzyme reactions

• Enzyme class: E.C.2.7.11.21 - polo kinase.
• Reaction:
  1. L-seryl-[protein] + ATP = O-phospho-L-seryl-[protein] + ADP + H⁺
  2. L-threonyl-[protein] + ATP = O-phospho-L-threonyl-[protein] + ADP + H⁺

Molecule diagrams generated from .mol files obtained from the KEGG ftp site

reference

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, G.de Cárcer, S.Ibañez, E.Bragado-Nilsson, G.Montoya.

ABSTRACT

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.