PDBsum entry 3wbl

Transferase/transferase inhibitor

PDB id: 3wbl

Contents

Protein chain

283 a.a.

Ligands

ACT

PDY

Waters ×108

PDB id:

3wbl

Name:

Transferase/transferase inhibitor

Title:

Crystal structure of cdk2 in complex with pyrazolopyrimidine inhibitor

Structure:

Cyclin-dependent kinase 2. Chain: a. Synonym: cell division protein kinase 2, p33 protein kinase. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: cdk2, cdkn2. Expressed in: trichoplusia ni. Expression_system_taxid: 7111.

Resolution:

2.00Å R-factor: 0.192 R-free: 0.249

Authors:

A.Fujino,K.Fukushima,T.Kubota,T.Kosugi,M.Takimoto-Kamimura

Key ref:

A.Fujino et al. (2013). Crystal structure of human cyclin-dependent kinase-2 complex with MK2 inhibitor TEI-I01800: insight into the selectivity. J Synchrotron Radiat, 20, 905-909. PubMed id: 24121337 DOI: 10.1107/S0909049513020736

Date:

20-May-13 Release date: 30-Oct-13

Protein chain

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

Seq: 298 a.a.

Struc: 283 a.a.

Enzyme reactions

• Enzyme class: 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⁺

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

reference

DOI no: 10.1107/S0909049513020736

J Synchrotron Radiat 20:905-909 (2013)

PubMed id: 24121337

Crystal structure of human cyclin-dependent kinase-2 complex with MK2 inhibitor TEI-I01800: insight into the selectivity.

A.Fujino, K.Fukushima, T.Kubota, T.Kosugi, M.Takimoto-Kamimura.

ABSTRACT

Mitogen-activated protein kinase-activated protein kinase 2 (MK2 or MAPKAP-K2) is a Ser/Thr kinase from the p38 mitogen-activated protein kinase signalling pathway and plays an important role in inflammatory diseases. The crystal structure of the MK2-TEI-I01800 complex has been reported; its Gly-rich loop was found to form an α-helix, not a β-sheet as has been observed for other Ser/Thr kinases. TEI-I01800 is 177-fold selective against MK2 compared with CDK2; in order to understand the inhibitory mechanism of TEI-I01800, the cyclin-dependent kinase 2 (CDK2) complex structure with TEI-I01800 was determined at 2.0 Å resolution. Interestingly, the Gly-rich loop of CDK2 formed a β-sheet that was different from that of MK2. In MK2, TEI-I01800 changed the secondary structure of the Gly-rich loop from a β-sheet to an α-helix by collision between Leu70 and a p-ethoxyphenyl group at the 7-position and bound to MK2. However, for CDK2, TEI-I01800 bound to CDK2 without this structural change and lost the interaction with the substituent at the 7-position. In summary, the results of this study suggest that the reason for the selectivity of TEI-I01800 is the favourable conformation of TEI-I01800 itself, making it suitable for binding to the α-form MK2.