PDBsum entry: 1zrz

Transferase

PDB id: 1zrz

Contents

Protein chain

312 a.a. *

Ligands

BI1

Waters ×42

* Residue conservation analysis

PDB id:

1zrz

Name:

Transferase

Title:

Crystal structure of the catalytic domain of atypical protein kinasE C-iota

Structure:

Protein kinasE C, iota. Chain: a. Fragment: catalytic domain, residues 224-587. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: prkci. Expressed in: spodoptera frugiperda. Expression_system_taxid: 7108.

Resolution:

3.00Å R-factor: 0.249 R-free: 0.333

Authors:

A.Messerschmidt,S.Macieira,M.Velarde,M.Baedeker,C.Benda, A.Jestel,H.Brandstetter,T.Neuefeind,M.Blaesse,Structural Proteomics In Europe (Spine)

Key ref:

A.Messerschmidt et al. (2005). Crystal structure of the catalytic domain of human atypical protein kinase C-iota reveals interaction mode of phosphorylation site in turn motif. J Mol Biol, 352, 918-931. PubMed id: 16125198 DOI: 10.1016/j.jmb.2005.07.060

Date:

23-May-05 Release date: 13-Sep-05

Protein chain

P41743  (KPCI_HUMAN) -  Protein kinase C iota type

Seq: 596 a.a.

Struc: 312 a.a.*

* PDB and UniProt seqs differ at 4 residue positions (black crosses)

Enzyme reactions

• Enzyme class: E.C.2.7.11.13 - Protein kinase C.
• Reaction: ATP + a protein = ADP + a phosphoprotein

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

 Gene Ontology (GO) functional annotation 

• Biological process: protein amino acid phosphorylation (1 term)
• Biochemical function: protein kinase activity (3 terms)

reference

DOI no: 10.1016/j.jmb.2005.07.060

J Mol Biol 352:918-931 (2005)

PubMed id: 16125198

Crystal structure of the catalytic domain of human atypical protein kinase C-iota reveals interaction mode of phosphorylation site in turn motif.

A.Messerschmidt, S.Macieira, M.Velarde, M.Bädeker, C.Benda, A.Jestel, H.Brandstetter, T.Neuefeind, M.Blaesse.

ABSTRACT

Atypical protein kinases C (aPKCs) play critical roles in signaling pathways that control cell growth, differentiation and survival. Therefore, they constitute attractive targets for the development of novel therapeutics against cancer. The crystal structure of the catalytic domain of atypical PKCiota in complex with the bis(indolyl)maleimide inhibitor BIM1 has been determined at 3.0A resolution within the frame of the European Structural Proteomics Project SPINE. The overall structure exhibits the classical bilobal kinase fold and is in its fully activated form. Both phosphorylation sites (Thr403 in the activation loop, and Thr555 in the turn motif) are well defined in the structure and form intramolecular ionic contacts that make an important contribution in stabilizing the active conformation of the catalytic subunit. The phosphorylation site in the hydrophobic motif of atypical PKCs is replaced by the phosphorylation mimic glutamate and this is also clearly seen in the structure of PKCiota (residue 574). This structure determination for the first time provides the architecture of the turn motif phosphorylation site, which is characteristic for PKCs and PKB/AKT, and is completely different from that in PKA. The bound BIM1 inhibitor blocks the ATP-binding site and puts the kinase domain into an intermediate open conformation. The PKCiota-BIM1 complex is the first kinase domain crystal structure of any atypical PKC and constitutes the basis for rational drug design for selective PKCiota inhibitors.

Selected figure(s)

Figure 3.
Figure 3. Stereo plot of the superposition of a typical closed, intermediate open and open conformation in ribbon representation. Closed conformation: PKA (PDB code: 1ATP31) cyan; intermediate closed conformation: PKCi, blue; open conformation: PKB/AKT (PDB code: 1GZK16) yellow. BIM1 and key residues of PKCi structure as well as His87 of PKA structure are in stick representation. Residue numbering is for PKCi except for His87, which is for PKA.

Figure 4.
Figure 4. Stereo plot of the BIM1 binding site with electron density for the inhibitor. The electron density is from a |2F[o] -F[c]| map contoured at 1.0 s. The inhibitor molecule and relevant residues are in stick representation.

The above figures are reprinted by permission from Elsevier: J Mol Biol (2005, 352, 918-931) copyright 2005.

Figures were selected by an automated process.