PDBsum entry 1fq1

Hydrolase/transferase

PDB id: 1fq1

Contents

Protein chains

183 a.a. *

296 a.a. *

Ligands

ATP

Metals

_MG

* Residue conservation analysis

References listed in PDB file

Key reference

Title

Phosphoprotein-Protein interactions revealed by the crystal structure of kinase-Associated phosphatase in complex with phosphocdk2.

Authors

H.Song, N.Hanlon, N.R.Brown, M.E.Noble, L.N.Johnson, D.Barford.

Ref.

Mol Cell, 2001, 7, 615-626. [DOI no: 10.1016/S1097-2765(01)00208-8]

PubMed id

11463386

Abstract

The CDK-interacting protein phosphatase KAP dephosphorylates phosphoThr-160 (pThr-160) of the CDK2 activation segment, the site of regulatory phosphorylation that is essential for kinase activity. Here we describe the crystal structure of KAP in association with pThr-160-CDK2, representing an example of a protein phosphatase in complex with its intact protein substrate. The major protein interface between the two molecules is formed by the C-terminal lobe of CDK2 and the C-terminal helix of KAP, regions remote from the kinase-activation segment and the KAP catalytic site. The kinase-activation segment interacts with the catalytic site of KAP almost entirely via the phosphate group of pThr-160. This interaction requires that the activation segment is unfolded and drawn away from the kinase molecule, inducing a conformation of CDK2 similar to the activated state observed in the CDK2/cyclin A complex.

Figure 1.
Figure 1. Structures of KAP and PTP1B(A) Stereo view showing a 2F[o]-F[c] electron density omit map contoured at 1σ in the vicinity of the catalytic Cys residue (Cys-140) of wild-type KAP revealing the formation of a disulphide bond to Cys-79.(B) Ribbon diagram comparing KAPt with PTP1B. The PTP loop of both molecules is shown in yellow, the acid/base loop (WPD loop) in red, and the Q loop in white. The pTyr recognition segment of PTP1B is in green. A sulfate ion and pTyr residue are shown at the catalytic sites of KAPt and PTP1B, respectively. Figures were created using AESOP (M. E. M. N., unpublished data), BOBSCRIPT (Esnouf, 1997), and Raster3D (Merit and Murphy, 1994)

Figure 4.
Figure 4. The Conformation of pCDK2 in the pCDK2/KAPt Complex Represents the Activated ConformationA structural comparison of CDK2 as the nonphosphorylated monomer in the pCDK2/cyclin A complex and in the pCDK2/KAPt complex. Except for differences in the conformation of the activation segment residues 152–165, the conformation of CDK2 in the pCDK2/cyclin A binary complex is most similar to the pCDK2/KAPt structure. The N- and C-terminal lobes of CDK2 are colored white and gold, respectively, and the C helix is shown in magenta. The activation segment is green, except for residues 153–164 that are disordered in monomeric pCDK2 and are shown in red

The above figures are reprinted by permission from Cell Press: Mol Cell (2001, 7, 615-626) copyright 2001.

Secondary reference #1

Title

Dephosphorylation of cdk2 thr160 by the cyclin-Dependent kinase-Interacting phosphatase kap in the absence of cyclin.

Authors

R.Y.Poon, T.Hunter.

Ref.

Science, 1995, 270, 90-93. [DOI no: 10.1126/science.270.5233.90]

PubMed id

7569954

Secondary reference #2

Title

Cdi1, A human g1 and s phase protein phosphatase that associates with cdk2.

Authors

J.Gyuris, E.Golemis, H.Chertkov, R.Brent.

Ref.

Cell, 1993, 75, 791-803. [DOI no: 10.1016/0092-8674(93)90498-F]

PubMed id

8242750

Secondary reference #3

Title

The p21 cdk-Interacting protein cip1 is a potent inhibitor of g1 cyclin-Dependent kinases.

Authors

J.W.Harper, G.R.Adami, N.Wei, K.Keyomarsi, S.J.Elledge.

Ref.

Cell, 1993, 75, 805-816. [DOI no: 10.1016/0092-8674(93)90499-G]

PubMed id

8242751