PDBsum entry 1a06

Kinase

PDB id: 1a06

Contents

Protein chain

279 a.a. *

Waters ×122

* Residue conservation analysis

PDB id:

1a06

Name:

Kinase

Title:

Calmodulin-dependent protein kinase from rat

Structure:

Calcium/calmodulin-dependent protein kinase. Chain: a. Engineered: yes

Source:

Rattus norvegicus. Norway rat. Organism_taxid: 10116. Organ: brain

Biol. unit:

Dimer (from PQS)

Resolution:

2.50Å R-factor: 0.201 R-free: 0.313

Authors:

J.Kuriyan,J.Goldberg

Key ref:

J.Goldberg et al. (1996). Structural basis for the autoinhibition of calcium/calmodulin-dependent protein kinase I. Cell, 84, 875-887. PubMed id: 8601311 DOI: 10.1016/S0092-8674(00)81066-1

Date:

09-Dec-97 Release date: 08-Apr-98

Protein chain

Q63450  (KCC1A_RAT) -  Calcium/calmodulin-dependent protein kinase type 1 from Rattus norvegicus

Seq: 374 a.a.

Struc: 279 a.a.

Enzyme reactions

• Enzyme class: E.C.2.7.11.17 - calcium/calmodulin-dependent 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⁺
• Cofactor: Ca(2+)

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

reference

DOI no: 10.1016/S0092-8674(00)81066-1

Cell 84:875-887 (1996)

PubMed id: 8601311

Structural basis for the autoinhibition of calcium/calmodulin-dependent protein kinase I.

J.Goldberg, A.C.Nairn, J.Kuriyan.

ABSTRACT

The crystal structure of calcium/calmodulin-dependent protein kinase I has been determined in the autoinhibited form. The C-terminal regulatory region of the enzyme forms a helix-loop-helix segment that extends across the two domains of the catalytic core, making multiple inhibitory interactions. Elements of the first regulatory alpha helix and the loop interfere with the binding site for peptide substrates, while the loop and the second helix interact with the ATP-binding domain to induce conformational changes that obstruct the nucleotide binding pocket. One part of the calmodulin recognition element protrudes away from the catalytic domain and is potentially available for an initial interaction with calmodulin. The structure provides a view of an intact calmodulin target and suggests that substantial structural changes will accompany kinase activation by calmodulin binding to the regulatory region.

Selected figure(s)

Figure 1.
Figure 1. Comparison of the Fold of Autoinhibited CaM Kinase I with cAPK(A) Ribbon drawing of CaM kinase I (CaMKI; left) and cAPK (right). The structures of autoinhibited CaMKI and cAPK are drawn with their C-terminal lobes (helical domain at bottom) in similar orientations. The cAPK structure is that of [69], with the PKI peptide inhibitor colored orange and the ATP shown in ball and stick form (entry 1ATP in the Brookhaven Protein Data Bank). cAPK has its two domains in a closed conformation whereas the CaMKI active site is opened by an 18° relative rotation of the domains, with respect to cAPK. The regulatory C-terminal sequence of CaMKI, containing the autoinhibitory region, is colored red (residues 285–316). The ATP-binding glycine-rich loop or P loop (colored green in both structures; residues 23–36 in CaMKI, 46–59 in cAPK) covers the ATP molecule in cAPK. In CaMKI, the P loop interacts with the autoinhibitory region and adopts a distinct conformation that distorts the ATP-binding site. Two disordered regions of CaMKI in the crystal structure are indicated with dotted lines (ten residues, 54–63, not modeled in the N-terminal domain, and eighteen residues, 164–181, in the C-terminal domain, are indicated by the corresponding number of dots). The region of CaM kinase I that is boxed is shown in detail in (B).(B) Stereo-diagram showing the interaction between the CaMKI regulatory segment (red, residues 285–316) and the catalytic core of the enzyme (gray). Selected residues of the regulatory region are drawn in white, and residues from the catalytic core are colored blue. Figure prepared using the programs MOLSCRIPT ([41]) and Raster3D ( [2]).

Figure 4.
Figure 4. Solvent-Accessible Surface of Autoinhibited CaMKIThe C-terminal sequence was omitted from the surface calculation and, instead, is drawn as a red tube (residues 280–316). The side chains of hydrophobic residues (Ala, Cys, Ile, Leu, Met, Phe, Trp, Tyr, and Val) that are located in the C-terminal region are drawn in yellow. The autoinhibitory sequence, defined by truncation mutagenesis ([25 and 65]) and by this structural study, is drawn in magenta. Figure was generated using the program GRASP ( [53]).

The above figures are reprinted by permission from Cell Press: Cell (1996, 84, 875-887) copyright 1996.

Figures were selected by an automated process.