1EES

SOLUTION STRUCTURE OF CDC42HS COMPLEXED WITH A PEPTIDE DERIVED FROM P-21 ACTIVATED KINASE, NMR, 20 STRUCTURES

Summary for 1EES

• Entry DOI: 10.2210/pdb1ees/pdb
• Related: 1AJE 1CEE 1CF4
• Descriptor: GTP-BINDING PROTEIN, P21-ACTIVATED KINASE (2 entities in total)
• Functional Keywords: protein-protein complex, structural protein
• Biological source: Homo sapiens (human); More
• Cellular location: Cell membrane; Lipid-anchor; Cytoplasmic side (Potential): P60953
• Total number of polymer chains: 2
• Total formula weight: 24892.32

Authors

Gizachew, D.,Guo, W.,Chohan, K.C.,Sutcliffe, M.J.,Oswald, R.E. (deposition date: 2000-02-02, release date: 2000-03-29, Last modification date: 2024-05-22)

Primary citation

Gizachew, D.,Guo, W.,Chohan, K.K.,Sutcliffe, M.J.,Oswald, R.E.
Structure of the complex of Cdc42Hs with a peptide derived from P-21 activated kinase.
Biochemistry, 39:3963-3971, 2000

PubMed Abstract: Cdc42Hs is a member of the Ras superfamily of GTPases and initiates a cascade that begins with the activation of several kinases, including p21-activated kinase (PAK). We have previously used a 46 amino acid fragment of PAK (PBD46) to define the binding surface on Cdc42Hs [Guo et al. (1998) Biochemistry 37, 14030-14037]. Here we describe the three-dimensional solution structure of the Cdc42Hs. GMPPCP-PBD46 complex. Heteronuclear NMR methods were used to assign resonances in the complex, and approximately 2400 distance and dihedral restraints were used to calculate a set of 20 structures using a combination of distance geometry, simulated annealing, and chemical shift and Ramachandran refinement. The overall structure of Cdc42Hs in the complex differs from the uncomplexed structure in two major aspects: (1) the first alpha helix is reoriented to accommodate the binding of the peptide and (2) the regions corresponding to switch I and switch II are less disordered. As suggested by our previous work (Guo et al., 1998) and similar to the complex between Cdc42Hs and fACK [Mott et al. (1999) Nature 399, 384-388], PBD46 forms an intermolecular beta-sheet with beta2 of Cdc42Hs and contacts both switch I and switch II. The extensive binding surface between PBD46 and Cdc42Hs can account for both the high affinity of the complex and the inhibition by PBD46 of GTP hydrolysis.

PubMed: 10747784
DOI: 10.1021/bi992646d

Experimental method

SOLUTION NMR