PDBsum entry 1fq1

Hydrolase/transferase

PDB id: 1fq1

Contents

Protein chains

183 a.a. *

296 a.a. *

Ligands

ATP

Metals

_MG

* Residue conservation analysis

PDB id:

1fq1

Name:

Hydrolase/transferase

Title:

Crystal structure of kinase associated phosphatase (kap) in complex with phospho-cdk2

Structure:

Cyclin-dependent kinase inhibitor 3. Chain: a. Engineered: yes. Mutation: yes. Cell division protein kinase 2. Chain: b. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Expressed in: escherichia coli. Expression_system_taxid: 562. Other_details: homo sapiens. Other_details: homo sapiens

Biol. unit:

Dimer (from PQS)

Resolution:

3.00Å R-factor: 0.235 R-free: 0.313

Authors:

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

Key ref:

H.Song et al. (2001). Phosphoprotein-protein interactions revealed by the crystal structure of kinase-associated phosphatase in complex with phosphoCDK2. Mol Cell, 7, 615-626. PubMed id: 11463386 DOI: 10.1016/S1097-2765(01)00208-8

Date:

01-Sep-00 Release date: 09-May-01

Protein chain

Q16667  (CDKN3_HUMAN) -  Cyclin-dependent kinase inhibitor 3 from Homo sapiens

Seq: 212 a.a.

Struc: 183 a.a.*

Protein chain

P24941  (CDK2_HUMAN) -  Cyclin-dependent kinase 2 from Homo sapiens

Seq: 298 a.a.

Struc: 296 a.a.*

* PDB and UniProt seqs differ at 2 residue positions (black crosses)

Enzyme reactions

• Enzyme class 1: Chain A: E.C.3.1.3.16 - protein-serine/threonine phosphatase.
• Reaction:
  1. O-phospho-L-seryl-[protein] + H2O = L-seryl-[protein] + phosphate
  2. O-phospho-L-threonyl-[protein] + H2O = L-threonyl-[protein] + phosphate
• Enzyme class 2: Chain A: E.C.3.1.3.48 - protein-tyrosine-phosphatase.
• Reaction: O-phospho-L-tyrosyl-[protein] + H2O = L-tyrosyl-[protein] + phosphate
• Enzyme class 3: Chain B: 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⁺

L-seryl-[protein] (Bound ligand (Het Group name = ATP) corresponds exactly) + ATP = O-phospho-L-seryl-[protein] + ADP + H(+)

L-threonyl-[protein] (Bound ligand (Het Group name = ATP) corresponds exactly) + ATP = O-phospho-L-threonyl-[protein] + ADP + H(+)

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: 10.1016/S1097-2765(01)00208-8

Mol Cell 7:615-626 (2001)

PubMed id: 11463386

Phosphoprotein-protein interactions revealed by the crystal structure of kinase-associated phosphatase in complex with phosphoCDK2.

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

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.

Selected figure(s)

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.

Figures were selected by an automated process.