PDBsum entry: 1h28

Cell cycle

PDB-id: 1h28

Asymmetric unit

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Description

Header details

Header records

References

PROCHECK

Protein chains

297 a.a. *

258 a.a. *

Ligands

GLY-SER-ALA-LYS-ARG-ARG-LEU-PHE-GLY-GLU

ALA-LYS-ARG-ARG-LEU-PHE-GLY-GLU

Waters ×37

* Residue conservation analysis

Tools

Clefts Calculation

Biological unit, trimer
- as defined in PDB file (see also PQS)

PDB id:

1h28

Name:

Cell cycle

Title:

Cdk2/cyclin a in complex with an 11-residue recruitment peptide from p107

Structure:

Cell division protein kinase 2. Chain: a, c. Synonym: cyclin-dependent kinase 2, p33 protein kinase, cdk2. Engineered: yes. Cyclin a2. Chain: b, d. Fragment: cyclin fold, residues 175-432. Synonym: cyclin a.

Source:

Homo sapiens. Human. Organism_taxid: 9606. Expressed in: escherichia coli. Expression_system_taxid: 562. Synthetic: yes. Organism_taxid: 9606

Biological unit:

Trimer (from PDB file)

UniProt:

Chains A, C: P24941 (CDK2_HUMAN)

Seq:
Struc:
	Seq:	298 a.a.
	Struc:	297 a.a.*

Chains B, D: P20248 (CCNA2_HUMAN)

Seq:

Struc:

Seq:

432 a.a.

Struc:

258 a.a.

Key:	PfamA domain
Secondary structure	CATH domain

* PDB and UniProt seqs differ at 1 residue position (black cross)

Enzyme class:

Chains A, C: E.C.2.7.11.22   [IntEnz]   [ExPASy]   [KEGG]   [BRENDA]

Reaction:

ATP + a protein = ADP + a phosphoprotein

Resolution:

2.8Å

R-factor:

0.246

R-free:

0.322

Authors:

I.Tews,K.Y.Cheng,E.D.Lowe,M.E.M.Noble,N.R.Brown,S.Gul, S.Gamblin,L.N.Johnson

Key ref:

E.D.Lowe et al. (2002). Specificity determinants of recruitment peptides bound to phospho-CDK2/cyclin A.. Biochemistry, 41, 15625-15634. [PubMed id: 12501191] [DOI: 10.1021/bi0268910]

Date:

31-Jul-02

Release date:

01-Feb-03

Related entries:

1aq1 human cyclin dependent kinase 2 complexed with the inhibitor staurosporine
1b38 human cyclin-dependent kinase 2
1b39 human cyclin-dependent kinase 2 phosphorylated on thr 160
1buh crystal structure of the human cdk2 kinase complex withcell cycle-regulatory protein ckshs1
1ckp human cyclin dependent kinase 2 complexed with the inhibitor purvalanol b
1di8 the structure of cyclin-dependent kinase 2 (cdk2) in complex with 4-[3- hydroxyanilino]-6,7-dimethoxyquinazoline
1dm2 human cyclin-dependent kinase 2 complexed with the inhibitor hymenialdisine
1e1v human cyclin dependent kinase 2 complexed with the inhibitor nu2058
1e1x human cyclin dependent kinase 2 complexed with the inhibitor nu6027
1e9h thr 160 phosphorylated cdk2 - human cyclin a3 complex with the inhibitor indirubin-5- sulphonate bound
... plus others (see Header records)

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Surface

Key reference

DOI no: 10.1021/bi0268910

Biochemistry 41:15625-15634 (2002)

PubMed id: 12501191

Specificity determinants of recruitment peptides bound to phospho-CDK2/cyclin A.

E.D.Lowe, I.Tews, K.Y.Cheng, N.R.Brown, S.Gul, M.E.Noble, S.J.Gamblin, L.N.Johnson.

ABSTRACT

Progression through S phase of the eukaryotic cell cycle is regulated by the action of the cyclin dependent protein kinase 2 (CDK2) in association with cyclin A. CDK2/cyclin A phosphorylates numerous substrates. Substrate specificity often employs a dual recognition strategy in which the sequence flanking the phospho-acceptor site (Ser.Pro.X.Arg/Lys) is recognized by CDK2, while the cyclin A component of the complex contains a hydrophobic site that binds Arg/Lys.X.Leu ("RXL" or "KXL") substrate recruitment motifs. To determine additional sequence specificity motifs around the RXL sequence, we have performed X-ray crystallographic studies at 2.3 A resolution and isothermal calorimetry measurements on complexes of phospho-CDK2/cyclin A with a recruitment peptide derived from E2F1 and with shorter 11-mer peptides from p53, pRb, p27, E2F1, and p107. The results show that the cyclin recruitment site accommodates a second hydrophobic residue either immediately C-terminal or next adjacent to the leucine of the "RXL" motif and that this site makes important contributions to the recruitment peptide recognition. The arginine of the RXL motif contacts a glutamate, Glu220, on the cyclin. In those substrates that contain a KXL motif, no ionic interactions are observed with the lysine. The sequences N-terminal to the "RXL" motif of the individual peptides show no conservation, but nevertheless make common contacts to the cyclin through main chain interactions. Thus, the recruitment site is able to recognize diverse but conformationally constrained target sequences. The observations have implications for the further identification of physiological substrates of CDK2/cyclin A and the design of specific inhibitors.