PDBsum entry 1h92

Transferase

PDB id: 1h92

Contents

Protein chain

63 a.a. *

* Residue conservation analysis

PDB id:

1h92

Name:

Transferase

Title:

Sh3 domain of human lck tyrosine kinase

Structure:

Proto-oncogene tyrosine-protein kinase lck. Chain: a. Fragment: sh3 domain residues 57-119. Synonym: tyrosine-protein kinase lck, p56-lck. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Cellular_location: intracellular. Expressed in: escherichia coli. Expression_system_taxid: 511693.

NMR struc:

30 models

Authors:

K.Schweimer,S.Hoffmann,U.Friedrich,B.Biesinger,P.Roesch,H.Sticht

Key ref:

K.Schweimer et al. (2002). Structural investigation of the binding of a herpesviral protein to the SH3 domain of tyrosine kinase Lck. Biochemistry, 41, 5120-5130. PubMed id: 11955060 DOI: 10.1021/bi015986j

Date:

22-Feb-01 Release date: 22-Oct-01

Protein chain

P06239  (LCK_HUMAN) -  Tyrosine-protein kinase Lck from Homo sapiens

Seq: 509 a.a.

Struc: 63 a.a.*

* PDB and UniProt seqs differ at 1 residue position (black cross)

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: 10.1021/bi015986j

Biochemistry 41:5120-5130 (2002)

PubMed id: 11955060

Structural investigation of the binding of a herpesviral protein to the SH3 domain of tyrosine kinase Lck.

K.Schweimer, S.Hoffmann, F.Bauer, U.Friedrich, C.Kardinal, S.M.Feller, B.Biesinger, H.Sticht.

ABSTRACT

Herpesvirus saimiri codes for a tyrosine kinase interacting protein (Tip) that interacts with both the SH3 domain and the kinase domain of the T-cell-specific tyrosine kinase Lck via two separate motifs. The activation of Lck by Tip is considered as a key event in the transformation of human T-lymphocytes during herpesviral infection. We investigated the interaction of proline-rich Tip peptides with the LckSH3 domain starting with the structural characterization of the unbound interaction partners. The solution structure of the LckSH3 was determined by heteronuclear multidimensional nuclear magnetic resonance (NMR) spectroscopy using 44 residual dipolar couplings in addition to the conventional experimental restraints. Circular dichroism spectroscopy proved that the polyproline helix of Tip is already formed prior to SH3 binding and is conformationally stable. NMR titration experiments point out three major regions of the Tip-Lck interaction comprising the RT loop, the n-src loop, and a helical turn preceding the last strand of the beta-sheet. Further changes of the chemical shifts were observed for the N- and C-terminal beta-strands of the SH3 domain, indicating additional contacts outside the proline-rich segment or subtle structural rearrangements transmitted from the binding site of the proline helix. Fluorescence spectroscopy shows that Tip binds to the SH3 domains of several Src kinases (Lck, Hck, Lyn, Src, Fyn, Yes), exhibiting the highest affinities for Lyn, Hck, and Lck.