PDBsum entry 5khx

Transferase/transferase inhibitor

PDB id: 5khx

Contents

Protein chain

278 a.a.

Ligands

6TE

Waters ×79

PDB id:

5khx

Name:

Transferase/transferase inhibitor

Title:

Crystal structure of jak1 in complex with pf-4950736

Structure:

Tyrosine-protein kinase jak1. Chain: a. 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:

2.40Å R-factor: 0.174 R-free: 0.242

Authors:

S.Han,N.L.Caspers

Key ref:

N.L.Caspers et al. (2016). Development of a high-throughput crystal structure-determination platform for JAK1 using a novel metal-chelator soaking system. Acta Crystallogr F Struct Biol Commun, 72, 840-845. PubMed id: 27827355 DOI: 10.1107/S2053230X16016356

Date:

16-Jun-16 Release date: 09-Nov-16

Protein chain

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

Seq: 1154 a.a.

Struc: 278 a.a.

Enzyme reactions

• Enzyme class: 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: 10.1107/S2053230X16016356

Acta Crystallogr F Struct Biol Commun 72:840-845 (2016)

PubMed id: 27827355

Development of a high-throughput crystal structure-determination platform for JAK1 using a novel metal-chelator soaking system.

N.L.Caspers, S.Han, F.Rajamohan, L.R.Hoth, K.F.Geoghegan, T.A.Subashi, M.L.Vazquez, N.Kaila, C.N.Cronin, E.Johnson, R.G.Kurumbail.

ABSTRACT

Crystals of phosphorylated JAK1 kinase domain were initially generated in complex with nucleotide (ADP) and magnesium. The tightly bound Mg²⁺-ADP at the ATP-binding site proved recalcitrant to ligand displacement. Addition of a molar excess of EDTA helped to dislodge the divalent metal ion, promoting the release of ADP and allowing facile exchange with ATP-competitive small-molecule ligands. Many kinases require the presence of a stabilizing ligand in the ATP site for crystallization. This procedure could be useful for developing co-crystallization systems with an exchangeable ligand to enable structure-based drug design of other protein kinases.