PDBsum entry 5bpy

Transferase/transferase inhibitor

PDB id: 5bpy

Contents

Protein chains

263 a.a.

247 a.a.

Ligands

4UQ ×2

Waters ×118

PDB id:

5bpy

Name:

Transferase/transferase inhibitor

Title:

Crystal structure of bruton agammaglobulinemia tyrosine kinase complexed with bms-824171 aka 6-[(3r)-3-(4-tert-bu tylbenzamido) piperidin-1-yl]-2-{[4-(morpholine-4-carbonyl) phenyl]amino}pyridine- 3-carboxamide

Structure:

Tyrosine-protein kinase btk. Chain: a, b. Synonym: agammaglobulinemia tyrosine kinase,atk,b-cell progenitor kinase,bpk,bruton tyrosine kinase. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: btk, agmx1, atk, bpk. Expressed in: baculovirus expression vector pfastbac1-hm. Expression_system_taxid: 274590.

Resolution:

2.31Å R-factor: 0.215 R-free: 0.242

Authors:

J.K.Muckelbauer

Key ref:

Q.Liu et al. (2015). Design and synthesis of carbazole carboxamides as promising inhibitors of Bruton's tyrosine kinase (BTK) and Janus kinase 2 (JAK2). Bioorg Med Chem Lett, 25, 4265-4269. PubMed id: 26320619 DOI: 10.1016/j.bmcl.2015.07.102

Date:

28-May-15 Release date: 23-Sep-15

Protein chain

Q06187  (BTK_HUMAN) -  Tyrosine-protein kinase BTK from Homo sapiens

Seq: 659 a.a.

Struc: 263 a.a.*

Protein chain

Q06187  (BTK_HUMAN) -  Tyrosine-protein kinase BTK from Homo sapiens

Seq: 659 a.a.

Struc: 247 a.a.*

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

Enzyme reactions

• Enzyme class: Chains A, B: E.C.2.7.10.2 - non-specific protein-tyrosine kinase.
• Reaction: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H⁺

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

Added reference

DOI no: 10.1016/j.bmcl.2015.07.102

Bioorg Med Chem Lett 25:4265-4269 (2015)

PubMed id: 26320619

Design and synthesis of carbazole carboxamides as promising inhibitors of Bruton's tyrosine kinase (BTK) and Janus kinase 2 (JAK2).

Q.Liu, D.G.Batt, J.S.Lippy, N.Surti, A.J.Tebben, J.K.Muckelbauer, L.Chen, Y.An, C.Chang, M.Pokross, Z.Yang, H.Wang, J.R.Burke, P.H.Carter, J.A.Tino.

ABSTRACT

Four series of disubstituted carbazole-1-carboxamides were designed and synthesised as inhibitors of Bruton's tyrosine kinase (BTK). 4,7- and 4,6-disubstituted carbazole-1-carboxamides were potent and selective inhibitors of BTK, while 3,7- and 3,6-disubstituted carbazole-1-carboxamides were potent and selective inhibitors of Janus kinase 2 (JAK2).