ISDA: 4K6Z

Deposition Date 2013-04-16

Release Date 2013-10-02

Last Version Date 2024-11-27

Entry Detail

PDB ID:

4K6Z

Keywords:

TRANSFERASE/TRANSFERASE INHIBITOR

Title:

The Jak1 kinase domain in complex with compound 37

Biological Source:

Source Organism(s):

Homo sapiens (Taxon ID: 9606)

Expression System(s):

Spodoptera frugiperda

Method Details:

Experimental Method:

X-RAY DIFFRACTION

Resolution:

2.73 Å

R-Value Free:

0.29

R-Value Work:

0.23

R-Value Observed:

0.24

Space Group:

P 21 21 2

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Macromolecular Entities

Structures with similar UniProt ID

Protein Blast

Polymer Type:polypeptide(L)
Molecule:Tyrosine-protein kinase JAK1
Gene (Uniprot):JAK1
Chain IDs:A
Chain Length:302
Number of Molecules:1
Biological Source:Homo sapiens

UniProt ID:P23458 Pfam ID:PF07714 EC:2.7.10.2

Modified Residue

Compound ID	Chain ID	Parent Comp ID	Details	2D Image
PTR	A	TYR	O-PHOSPHOTYROSINE

Ligand Molecules

1Q3

Primary Citation

Design and evaluation of novel 8-oxo-pyridopyrimidine Jak1/2 inhibitors.

Labadie, S, Barrett, K, Blair, W.S, Chang, C, Deshmukh, G, Eigenbrot, C, Gibbons, P, Johnson, A, Kenny, J.R, Kohli, P.B, Liimatta, M, Lupardus, P.J, Shia, S, Steffek, M, Ubhayakar, S, Abbema, A.V, Zak, M.Show

Bioorg. Med. Chem. Lett. 23 5923 5930 (2013)

PMID: 24042009 DOI: 10.1016/j.bmcl.2013.08.082

Abstact

A highly ligand efficient, novel 8-oxo-pyridopyrimidine containing inhibitor of Jak1 and Jak2 isoforms with a pyridone moiety as the hinge-binding motif was discovered. Structure-based design strategies were applied to significantly improve enzyme potency and the polarity of the molecule was adjusted to gain cellular activity. The crystal structures of two representative inhibitors bound to Jak1 were obtained to enable SAR exploration.

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Protein

Chemical

Disease

Primary Citation of related structures

Abstact

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