Loading
PDBj
MenuPDBj@FacebookPDBj@X(formerly Twitter)PDBj@BlueSkyPDBj@YouTubewwPDB FoundationwwPDB
RCSB PDBPDBeBMRBAdv. SearchSearch help

4F7J

Crystal structure of human CDK8/CYCC in complex with compound 3 (1-[3-tert-butyl-1-(4-methylphenyl)-1H-pyrazol-5-yl]-3-(2-hydroxyethyl)urea)

Summary for 4F7J
Entry DOI10.2210/pdb4f7j/pdb
Related4F6S 4F6U 4F6W 4F70 4F7L 4F7N
DescriptorCyclin-dependent kinase 8, Cyclin-C, 1-[3-tert-butyl-1-(4-methylphenyl)-1H-pyrazol-5-yl]-3-(2-hydroxyethyl)urea, ... (6 entities in total)
Functional Keywordsprotein kinase complex, proteros, transferase-transcription-inhibitor complex, transferase/transcription/inhibitor
Biological sourceHomo sapiens (human)
More
Cellular locationNucleus : P49336 P24863
Total number of polymer chains2
Total formula weight81125.42
Authors
Schneider, E.V.,Boettcher, J.,Huber, R.,Maskos, K. (deposition date: 2012-05-16, release date: 2013-05-01, Last modification date: 2023-09-13)
Primary citationSchneider, E.V.,Bottcher, J.,Huber, R.,Maskos, K.,Neumann, L.
Structure-kinetic relationship study of CDK8/CycC specific compounds.
Proc.Natl.Acad.Sci.USA, 110:8081-8086, 2013
Cited by
PubMed 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.
PubMed: 23630251
DOI: 10.1073/pnas.1305378110
PDB entries with the same primary citation
Experimental method
X-RAY DIFFRACTION (2.6 Å)
Structure validation

227561

PDB entries from 2024-11-20

PDB statisticsPDBj update infoContact PDBjnumon