PDBsum entry 4z32

Transferase

PDB id: 4z32

Contents

Protein chains

441 a.a.

(+ 0 more) 418 a.a.

Waters ×12

PDB id:

4z32

Name:

Transferase

Title:

Crystal structure of the ferm-sh2 domains of jak2

Structure:

Tyrosine-protein kinase jak2. Chain: a, b, c, d, e, f, g, h. Synonym: janus kinase 2,jak-2. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: jak2. Expressed in: trichoplusia ni. Expression_system_taxid: 7111

Resolution:

3.04Å R-factor: 0.258 R-free: 0.276

Authors:

R.Mcnally,M.J.Eck

Key ref:

R.McNally et al. (2016). Crystal Structure of the FERM-SH2 Module of Human Jak2. Plos One, 11, e0156218. PubMed id: 27227461 DOI: 10.1371/journal.pone.0156218

Date:

30-Mar-15 Release date: 22-Jun-16

Protein chains

O60674  (JAK2_HUMAN) -  Tyrosine-protein kinase JAK2 from Homo sapiens

Seq: 1132 a.a.

Struc: 441 a.a.

Protein chains

O60674  (JAK2_HUMAN) -  Tyrosine-protein kinase JAK2 from Homo sapiens

Seq: 1132 a.a.

Struc: 418 a.a.

Enzyme reactions

• Enzyme class: Chains A, B, C, D, E, F, G, H: 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: 10.1371/journal.pone.0156218

Plos One 11:e0156218 (2016)

PubMed id: 27227461

Crystal Structure of the FERM-SH2 Module of Human Jak2.

R.McNally, A.V.Toms, M.J.Eck.

ABSTRACT

Jak-family tyrosine kinases mediate signaling from diverse cytokine receptors. Binding of Jaks to their cognate receptors is mediated by their N-terminal region, which contains FERM and SH2 domains. Here we describe the crystal structure of the FERM-SH2 region of Jak2 at 3.0Å resolution. The structure reveals that these domains and their flanking linker segments interact intimately to form an integrated structural module. The Jak2 FERM-SH2 structure closely resembles that recently described for Tyk2, another member of the Jak family. While the overall architecture and interdomain orientations are preserved between Jak2 and Tyk2, we identify residues in the putative receptor-binding groove that differ between the two and may contribute to the specificity of receptor recognition. Analysis of Jak mutations that are reported to disrupt receptor binding reveals that they lie in the hydrophobic core of the FERM domain, and are thus expected to compromise the structural integrity of the FERM-SH2 unit. Similarly, analysis of mutations in Jak3 that are associated with severe combined immunodeficiency suggests that they compromise Jak3 function by destabilizing the FERM-SH2 structure.