The University of Southampton
University of Southampton Institutional Repository

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

Lowe, Edward D, Tews, Ivo, Cheng, Kin Yip, Brown, Nick R, Gul, Sheraz, Noble, Martin E M, Gamblin, Steven J and Johnson, Louise N (2002) Specificity determinants of recruitment peptides bound to phospho-CDK2/cyclin A Biochemistry, 41, (52), pp. 15625-15634. (doi:10.1021/bi0268910). (PMID:12501191).

Record type: Article


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.

PDF Biochem_41-15625.pdf - Version of Record
Restricted to Repository staff only
Download (626kB)
PDF Biochem_41-15625supp.pdf - Other
Restricted to Repository staff only
Download (26kB)

More information

Published date: 31 December 2002
Organisations: Centre for Biological Sciences


Local EPrints ID: 200657
ISSN: 0006-2960
PURE UUID: 3b3668b6-c665-40be-8d8e-af7db3cdb863
ORCID for Ivo Tews: ORCID iD

Catalogue record

Date deposited: 02 Nov 2011 14:27
Last modified: 18 Jul 2017 11:13

Export record



Author: Edward D Lowe
Author: Ivo Tews ORCID iD
Author: Kin Yip Cheng
Author: Nick R Brown
Author: Sheraz Gul
Author: Martin E M Noble
Author: Steven J Gamblin
Author: Louise N Johnson

University divisions

Download statistics

Downloads from ePrints over the past year. Other digital versions may also be available to download e.g. from the publisher's website.

View more statistics

Atom RSS 1.0 RSS 2.0

Contact ePrints Soton:

ePrints Soton supports OAI 2.0 with a base URL of

This repository has been built using EPrints software, developed at the University of Southampton, but available to everyone to use.

We use cookies to ensure that we give you the best experience on our website. If you continue without changing your settings, we will assume that you are happy to receive cookies on the University of Southampton website.