PDBsum entry 4f7n

Transferase/transcription/inhibitor

PDB id: 4f7n

Contents

Protein chains

334 a.a.

268 a.a.

Ligands

0SV

EDO ×2

Waters ×61

PDB id:

4f7n

Name:

Transferase/transcription/inhibitor

Title:

Crystal structure of human cdk8/cycc in complex with compound 11 (1- [3-tert-butyl-1-(4-methylphenyl)-1h-pyrazol-5-yl]-3-(5- hydroxypentyl)urea)

Structure:

Cyclin-dependent kinase 8. Chain: a. Fragment: unp residues 1-403. Synonym: cell division protein kinase 8, mediator complex subunit cdk8, mediator of RNA polymerase ii transcription subunit cdk8, protein kinase k35. Engineered: yes. Cyclin-c. Chain: b.

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: cdk8. Expressed in: spodoptera frugiperda. Expression_system_taxid: 7108. Gene: ccnc.

Resolution:

2.65Å R-factor: 0.200 R-free: 0.228

Authors:

E.V.Schneider,J.Boettcher,R.Huber,K.Maskos

Key ref:

E.V.Schneider et al. (2013). Structure-kinetic relationship study of CDK8/CycC specific compounds. Proc Natl Acad Sci U S A, 110, 8081-8086. PubMed id: 23630251 DOI: 10.1073/pnas.1305378110

Date:

16-May-12 Release date: 01-May-13

Protein chain

P49336  (CDK8_HUMAN) -  Cyclin-dependent kinase 8 from Homo sapiens

Seq: 464 a.a.

Struc: 334 a.a.

Protein chain

P24863  (CCNC_HUMAN) -  Cyclin-C from Homo sapiens

Seq: 283 a.a.

Struc: 268 a.a.

Enzyme reactions

• Enzyme class 1: Chain A: 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⁺
• Enzyme class 2: Chain A: E.C.2.7.11.23 - [RNA-polymerase]-subunit kinase.
• Reaction: [DNA-directed RNA polymerase] + ATP = phospho-[DNA-directed RNA polymerase] + ADP + H⁺
• Enzyme class 3: Chain B: E.C.?

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: 10.1073/pnas.1305378110

Proc Natl Acad Sci U S A 110:8081-8086 (2013)

PubMed id: 23630251

Structure-kinetic relationship study of CDK8/CycC specific compounds.

E.V.Schneider, J.Böttcher, R.Huber, K.Maskos, L.Neumann.

ABSTRACT

In contrast with the very well explored concept of structure-activity relationship, similar studies are missing for the dependency between binding kinetics and compound structure of a protein ligand complex, the structure-kinetic relationship. Here, we present a structure-kinetic relationship study of the cyclin-dependent kinase 8 (CDK8)/cyclin C (CycC) complex. The scaffold moiety of the compounds is anchored in the kinase deep pocket and extended with diverse functional groups toward the hinge region and the front pocket. These variations can cause the compounds to change from fast to slow binding kinetics, resulting in an improved residence time. The flip of the DFG motif ("DMG" in CDK8) to the inactive DFG-out conformation appears to have relatively little influence on the velocity of binding. Hydrogen bonding with the kinase hinge region contributes to the residence time but has less impact than hydrophobic complementarities within the kinase front pocket.