PDBsum entry 3g33

Cell cycle

PDB id: 3g33

Contents

Protein chains

291 a.a. *

229 a.a. *

* Residue conservation analysis

PDB id:

3g33

Name:

Cell cycle

Title:

Crystal structure of cdk4/cyclin d3

Structure:

Cell division protein kinase 4. Chain: a, c. Synonym: cyclin-dependent kinase 4, psk-j3. Engineered: yes. Ccnd3 protein. Chain: b, d. Synonym: cyclin d3, isoform cra_b. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: cdk4. Expressed in: spodoptera frugiperda. Expression_system_taxid: 7108. Gene: ccnd3, hcg_16683. Expression_system_taxid: 7108

Resolution:

3.00Å R-factor: 0.283 R-free: 0.314

Authors:

T.Takaki,A.Echalier,N.R.Brown,T.Hunt,J.A.Endicott,M.E.M.Noble

Key ref:

T.Takaki et al. (2009). The structure of CDK4/cyclin D3 has implications for models of CDK activation. Proc Natl Acad Sci U S A, 106, 4171-4176. PubMed id: 19237555 DOI: 10.1073/pnas.0809674106

Date:

01-Feb-09 Release date: 10-Mar-09

Protein chains

P11802  (CDK4_HUMAN) -  Cyclin-dependent kinase 4 from Homo sapiens

Seq: 303 a.a.

Struc: 291 a.a.

Protein chains

P30281  (CCND3_HUMAN) -  G1/S-specific cyclin-D3 from Homo sapiens

Seq: 292 a.a.

Struc: 229 a.a.

Enzyme reactions

• Enzyme class 1: Chains A, C: E.C.2.7.11.22 - cyclin-dependent 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⁺
• Enzyme class 2: Chains B, D: E.C.?

Note, where more than one E.C. class is given (as above), each may correspond to a different protein domain or, in the case of polyprotein precursors, to a different mature protein.

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

reference

DOI no: 10.1073/pnas.0809674106

Proc Natl Acad Sci U S A 106:4171-4176 (2009)

PubMed id: 19237555

The structure of CDK4/cyclin D3 has implications for models of CDK activation.

T.Takaki, A.Echalier, N.R.Brown, T.Hunt, J.A.Endicott, M.E.Noble.

ABSTRACT

Cyclin-dependent kinase 4 (CDK4)/cyclin D complexes are expressed early in the G(1) phase of the cell cycle and stimulate the expression of genes required for G(1) progression by phosphorylation of the product of the retinoblastoma gene, pRb. To elaborate the molecular pathway of CDK4 activation and substrate selection we have determined the structure of nonphosphorylated CDK4/cyclin D3. This structure of an authentic CDK/cyclin complex shows that cyclin binding may not be sufficient to drive the CDK active site toward an active conformation. Phosphorylated CDK4/cyclin D3 is active as a pRb kinase and is susceptible to inhibition by p27(Kip1). Unlike CDK2/cyclin A, CDK4/cyclin D3 can be inactivated by treatment with lambda-phosphatase, implying that phosphorylated T172 is accessible to a generic phosphatase while bound to a cyclin. Taken together, these results suggest that the structural mechanism of CDK4/cyclin D3 activation differs markedly from that of previously studied CDK/cyclin complexes.

Selected figure(s)

Figure 1.
Structure and substrate selection in CDK4/cyclin D3. (A) The fold of CDK4/cyclin D3 (left side) is compared with that of CDK2/cyclin A in complex with a substrate peptide (PDB ID code 1QMZ; right side). Important structural and regulatory elements referred to in the text are indicated on each structure and correspond to the CDK N-lobe (light gray), the C-helix (cyan), the CDK C-lobe (yellow), the activation segment (red), and the cyclin subunit (green). (B) The activity of CDK4/cyclin D3 toward pRb family members highly depends on substrate recruitment. See Results for details.

Figure 2.
Comparison of the structures of monomeric CDK2, CDK4/cyclin D3, and T160pCDK2/cyclin A. The 3 structures are viewed looking down onto the CDK C-terminal domain from the N-terminal domain and are colored according to the scheme used in Fig. 1. (A) Monomeric CDK2. (B) CDK4/cyclin D3. (C) T160pCDK2/cyclin A. The figure highlights the displacement of the CDK4/cyclin D3 activation segment away from the active conformation present in T160pCDK2/cyclin A and its similarity to the structure of the activation segment in monomeric CDK2 (monomeric T160pCDK2 PDB ID code 1HCK).

Figures were selected by an automated process.