3NYX

Non-phosphorylated TYK2 JH1 domain with Quinoline-Thiadiazole-Thiophene Inhibitor

Summary for 3NYX

• Entry DOI: 10.2210/pdb3nyx/pdb
• Related: 3NZ0
• Descriptor: Non-receptor tyrosine-protein kinase TYK2, N-{5-[(7-chloroquinolin-4-yl)sulfanyl]-1,3,4-thiadiazol-2-yl}thiophene-2-carboxamide, 2,3-DIHYDROXY-1,4-DITHIOBUTANE, ... (4 entities in total)
• Functional Keywords: protein kinase, tyrosine phosphorylation, transferase, transferase-transferase inhibitor complex, transferase/transferase inhibitor
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 1
• Total formula weight: 35715.48

Authors

Eigenbrot, C.,Ultsch, M. (deposition date: 2010-07-15, release date: 2010-10-20, Last modification date: 2023-09-06)

Primary citation

Tsui, V.,Gibbons, P.,Ultsch, M.,Mortara, K.,Chang, C.,Blair, W.,Pulk, R.,Stanley, M.,Starovasnik, M.,Williams, D.,Lamers, M.,Leonard, P.,Magnuson, S.,Liang, J.,Eigenbrot, C.
A new regulatory switch in a JAK protein kinase.
Proteins, 79:393-401, 2011

PubMed Abstract: Members of the JAK family of protein kinases mediate signal transduction from cytokine receptors to transcription factor activation. Over-stimulation of these pathways is causative in immune disorders like rheumatoid arthritis, psoriasis, lupus, and Crohn's disease. A search for selective inhibitors of a JAK kinase has led to our characterization of a previously unknown kinase conformation arising from presentation of Tyr962 of TYK2 to an inhibitory small molecule via an H-bonding interaction. A small minority of protein kinase domains has a Tyrosine residue in this position within the αC-β4 loop, and it is the only amino acid commonly seen here with H-bonding potential. These discoveries will aid design of inhibitors that discriminate among the JAK family and more widely among protein kinases.

PubMed: 21117080
DOI: 10.1002/prot.22889

Experimental method

X-RAY DIFFRACTION (2.5 Å)