PDBsum entry 1ol6

Transferase

PDB id: 1ol6

Contents

Protein chain

246 a.a. *

Ligands

ATP

Waters ×3

* Residue conservation analysis

PDB id:

1ol6

Name:

Transferase

Title:

Structure of unphosphorylated d274n mutant of aurora-a

Structure:

Serine/threonine kinase 6. Chain: a. Fragment: catalytic domain, residues 122-403. Synonym: serine/threonine kinase 15, aurora/ipl1-related kinase 1, aurora-related kinase 1, hark1, aurora-a, breast-tumor-amplified kinase. Engineered: yes. Mutation: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Expressed in: escherichia coli. Expression_system_taxid: 562.

Resolution:

3.00Å R-factor: 0.277 R-free: 0.301

Authors:

R.Bayliss,E.Conti

Key ref:

R.Bayliss et al. (2003). Structural basis of Aurora-A activation by TPX2 at the mitotic spindle. Mol Cell, 12, 851-862. PubMed id: 14580337 DOI: 10.1016/S1097-2765(03)00392-7

Date:

06-Aug-03 Release date: 30-Oct-03

Protein chain

O14965  (AURKA_HUMAN) -  Aurora kinase A from Homo sapiens

Seq: 403 a.a.

Struc: 246 a.a.*

* PDB and UniProt seqs differ at 1 residue position (black cross)

Enzyme reactions

• Enzyme class: E.C.2.7.11.1 - non-specific serine/threonine protein 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⁺

L-seryl-[protein] (Bound ligand (Het Group name = ATP) corresponds exactly) + ATP = O-phospho-L-seryl-[protein] + ADP + H(+)

L-threonyl-[protein] (Bound ligand (Het Group name = ATP) corresponds exactly) + ATP = O-phospho-L-threonyl-[protein] + ADP + H(+)

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

reference

DOI no: 10.1016/S1097-2765(03)00392-7

Mol Cell 12:851-862 (2003)

PubMed id: 14580337

Structural basis of Aurora-A activation by TPX2 at the mitotic spindle.

R.Bayliss, T.Sardon, I.Vernos, E.Conti.

ABSTRACT

Aurora-A is an oncogenic kinase essential for mitotic spindle assembly. It is activated by phosphorylation and by the microtubule-associated protein TPX2, which also localizes the kinase to spindle microtubules. We have uncovered the molecular mechanism of Aurora-A activation by determining crystal structures of its phosphorylated form both with and without a 43 residue long domain of TPX2 that we identified as fully functional for kinase activation and protection from dephosphorylation. In the absence of TPX2, the Aurora-A activation segment is in an inactive conformation, with the crucial phosphothreonine exposed and accessible for deactivation. Binding of TPX2 triggers no global conformational changes in the kinase but pulls on the activation segment, swinging the phosphothreonine into a buried position and locking the active conformation. The recognition between Aurora-A and TPX2 resembles that between the cAPK catalytic core and its flanking regions, suggesting this molecular mechanism may be a recurring theme in kinase regulation.

Selected figure(s)

Figure 3.
Figure 3. Structure of Aurora-A Bound to TPX2(A) View of the complex between the catalytic domain of human Aurora (AuroraΔN, yellow) and the N-terminal domain of TPX2 shown in typical kinase orientation. An upstream stretch of TPX2 (red) binds at the N-terminal lobe of Aurora-A, and a downstream stretch (pink) binds between the two lobes. A dotted line in pink marks the approximate path of the linker connecting the two TPX2 stretches (disordered and not modeled).(B) View of the complex after a 180° rotation about the vertical axis in respect to view in (A) shows more clearly the two stretches of TPX2 binding to Aurora-A.(C) The upstream stretch of TPX2 (red, residues 7–21^TPX) binds at a hydrophobic surface groove present in the N-terminal lobe of the kinase (gray cartoon, yellow side chains). Details of the extensive interactions are shown in the same orientation as in (B). Aurora-A residues are labeled in black, and TPX2 residue labels are color coded as the structure.(D) The downstream helical stretch of TPX2 (pink, residues 30–43^TPX) binds Aurora-A near helix αC and the activation segment, close to but not directly in contact with phospho-Thr288^AUR (green). Details of interactions are shown in the same orientation as in (B) and (C).

Figure 5.
Figure 5. TPX2-Aurora-A Intermolecular Interactions Resemble cAPK Intramolecular Interactions(A and B) Transparent surfaces representing the conserved catalytic cores of (A) Aurora-A and (B) cAPK show similar surface grooves in the N-terminal lobe (between helix αC and the β sheet, gray cartoon) and a similar pocket between the two lobes (formed by the activation segment and helix αC, gray cartoon). The portions of TPX2 binding to Aurora-A are shown in red and pink (A), and the N- and C-terminal extensions to the cAPK catalytic core are shown in light blue (B).(C and D) Schematic diagram of the intermolecular interactions between Aurora-A and TPX2 (pink and red) and of the cAPK intramolecular interactions (light blue) shows that their mode of recognition at the atomic level is rather similar. The hydrophobic interactions of Tyr8^TPX, Tyr10^TPX, Trp34^TPX, and Phe35^TPX are recapitulated by Phe347^cAPK, Phe350^cAPK, Trp30^cAPK, and Phe26^cAPK.

The above figures are reprinted by permission from Cell Press: Mol Cell (2003, 12, 851-862) copyright 2003.

Figures were selected by an automated process.