PDBsum entry 5e1e

Transferase

PDB id

5e1e

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Contents

			Protein chains

					281 a.a.

			Ligands

					PEG


					5JG ×2

			Waters ×227

PDB id:

5e1e

Links

Name:

Transferase

Title:

Human jak1 kinase in complex with compound 30 at 2.30 angstroms resolution

Structure:

Tyrosine-protein kinase jak1. Chain: a, b. Fragment: protein kinase 2 domain residues 865-1154. Synonym: janus kinase 1,jak-1. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: jak1, jak1a, jak1b. Expressed in: spodoptera frugiperda. Expression_system_taxid: 7108

Resolution:

2.30Å

R-factor:

0.227

R-free:

0.268

Authors:

A.D.Ferguson

Key ref:

M.M.Vasbinder et al. (2016). Identification of azabenzimidazoles as potent JAK1 selective inhibitors. Bioorg Med Chem Lett, 26, 60-67. PubMed id: 26614408 DOI: 10.1016/j.bmcl.2015.11.031

Date:

29-Sep-15

Release date:

25-Nov-15

PROCHECK

	Headers

	References

Protein chains

P23458 (JAK1_HUMAN) - Tyrosine-protein kinase JAK1 from Homo sapiens

Seq: Struc:

Seq: Struc:

Seq: Struc:					1154 a.a. 281 a.a.

Key:

PfamA domain

Secondary structure

CATH domain



		Enzyme reactions

Enzyme class:

E.C.2.7.10.2 - non-specific protein-tyrosine kinase.

[IntEnz] [ExPASy] [KEGG] [BRENDA]

Reaction:

L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H⁺

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.2015.11.031	Bioorg Med Chem Lett 26:60-67 (2016)
PubMed id: 26614408

Identification of azabenzimidazoles as potent JAK1 selective inhibitors.
M.M.Vasbinder, M.Alimzhanov, M.Augustin, G.Bebernitz, K.Bell, C.Chuaqui, T.Deegan, A.D.Ferguson, K.Goodwin, D.Huszar, A.Kawatkar, S.Kawatkar, J.Read, J.Shi, S.Steinbacher, H.Steuber, Q.Su, D.Toader, H.Wang, R.Woessner, A.Wu, M.Ye, M.Zinda.

ABSTRACT

We have identified a class of azabenzimidazoles as potent and selective JAK1 inhibitors. Investigations into the SAR are presented along with the structural features required to achieve selectivity for JAK1 versus other JAK family members. An example from the series demonstrated highly selective inhibition of JAK1 versus JAK2 and JAK3, along with inhibition of pSTAT3 in vivo, enabling it to serve as a JAK1 selective tool compound to further probe the biology of JAK1 selective inhibitors.