PDBsum entry: 1ees

Structural protein

PDB id: 1ees

Contents

Protein chains

178 a.a. *

46 a.a. *

* Residue conservation analysis

PDB id:

1ees

Name:

Structural protein

Title:

Solution structure of cdc42hs complexed with a peptide derived from p-21 activated kinase, nmr, 20 structures

Structure:

Gtp-binding protein. Chain: a. Fragment: amino acids 1-178. Synonym: cdc42hs. Engineered: yes. P21-activated kinase. Chain: b. Fragment: amino acids 65-108. Synonym: mpak-3.

Source:

Homo sapiens. Human. Organism_taxid: 9606. Organ: placenta. Expressed in: escherichia coli. Expression_system_taxid: 562. Mus musculus. House mouse. Organism_taxid: 10090.

NMR struc:

20 models

Authors:

D.Gizachew,W.Guo,K.C.Chohan,M.J.Sutcliffe,R.E.Oswald

Key ref:

D.Gizachew et al. (2000). Structure of the complex of Cdc42Hs with a peptide derived from P-21 activated kinase. Biochemistry, 39, 3963-3971. PubMed id: 10747784 DOI: 10.1021/bi992646d

Date:

02-Feb-00 Release date: 29-Mar-00

Protein chain

P60953  (CDC42_HUMAN) -  Cell division control protein 42 homolog

Seq: 191 a.a.

Struc: 178 a.a.

Protein chain

Q61036  (PAK3_MOUSE) -  Serine/threonine-protein kinase PAK 3

Seq: 559 a.a.

Struc: 46 a.a.*

* PDB and UniProt seqs differ at 2 residue positions (black crosses)

Enzyme reactions

• Enzyme class: Chain B: E.C.2.7.11.1 - Non-specific serine/threonine protein kinase.
• Reaction: ATP + a protein = ADP + a phosphoprotein

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

 Gene Ontology (GO) functional annotation 

• Cellular component: mitotic spindle (12 terms)
• Biological process: positive regulation of cell cycle cytokinesis (20 terms)
• Biochemical function: nucleotide binding (5 terms)

reference

DOI no: 10.1021/bi992646d

Biochemistry 39:3963-3971 (2000)

PubMed id: 10747784

Structure of the complex of Cdc42Hs with a peptide derived from P-21 activated kinase.

D.Gizachew, W.Guo, K.K.Chohan, M.J.Sutcliffe, R.E.Oswald.

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.