PDBsum entry 1jeg

Transferase/hydrolase

PDB id: 1jeg

Contents

Protein chains

60 a.a. *

18 a.a. *

* Residue conservation analysis

PDB id:

1jeg

Name:

Transferase/hydrolase

Title:

Solution structure of the sh3 domain from c-terminal src kinase complexed with a peptide from the tyrosine phosphatase pep

Structure:

Tyrosine-protein kinase csk. Chain: a. Fragment: sh3 domain. Synonym: c-src kinase, protein-tyrosine kinase cyl. Engineered: yes. Hematopoietic cell protein-tyrosine phosphatase 70z-pep. Chain: b. Fragment: 25 residue peptide (residues 612-629). Engineered: yes

Source:

Mus musculus. House mouse. Organism_taxid: 10090. Expressed in: escherichia coli. Expression_system_taxid: 562. Expression_system_taxid: 562

NMR struc:

25 models

Authors:

R.Ghose,A.Shekhtman,M.J.Goger,H.Ji,D.Cowburn

Key ref:

R.Ghose et al. (2001). A novel, specific interaction involving the Csk SH3 domain and its natural ligand. Nat Struct Biol, 8, 998. PubMed id: 11685249 DOI: 10.1038/nsb1101-998

Date:

17-Jun-01 Release date: 31-Oct-01

Protein chain

P41241  (CSK_MOUSE) -  Tyrosine-protein kinase CSK from Mus musculus

Seq: 450 a.a.

Struc: 60 a.a.

Protein chain

P29352  (PTN22_MOUSE) -  Tyrosine-protein phosphatase non-receptor type 22 from Mus musculus

Seq: 802 a.a.

Struc: 18 a.a.

Enzyme reactions

• Enzyme class 1: Chain A: E.C.2.7.10.2 - non-specific protein-tyrosine kinase.
• Reaction: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H⁺
• Enzyme class 2: Chain B: E.C.3.1.3.48 - protein-tyrosine-phosphatase.
• Reaction: O-phospho-L-tyrosyl-[protein] + H2O = L-tyrosyl-[protein] + phosphate

Note, where more than one E.C. class is given (as above), each may correspond to a different protein domain or, in the case of polyprotein precursors, to a different mature protein.

Molecule diagrams generated from .mol files obtained from the KEGG ftp site

reference

DOI no: 10.1038/nsb1101-998

Nat Struct Biol 8:998 (2001)

PubMed id: 11685249

A novel, specific interaction involving the Csk SH3 domain and its natural ligand.

R.Ghose, A.Shekhtman, M.J.Goger, H.Ji, D.Cowburn.

ABSTRACT

C-terminal Src kinase (Csk) takes part in a highly specific, high affinity interaction via its Src homology 3 (SH3) domain with the proline-enriched tyrosine phosphatase PEP in hematopoietic cells. The solution structure of the Csk-SH3 domain in complex with a 25-residue peptide from the Pro/Glu/Ser/Thr-rich (PEST) domain of PEP reveals the basis for this specific peptide recognition motif involving an SH3 domain. Three residues, Ala 40, Thr 42 and Lys 43, in the SH3 domain of Csk specifically recognize two hydrophobic residues, Ile 625 and Val 626, in the proline-rich sequence of the PEST domain of PEP. These two residues are C-terminal to the conventional proline-rich SH3 domain recognition sequence of PEP. This interaction is required in addition to the classic polyproline helix (PPII) recognition by the Csk-SH3 domain for the association between Csk and PEP in vivo. NMR relaxation analysis suggests that Csk-SH3 has different dynamic properties in the various subsites important for peptide recognition.

Selected figure(s)

Figure 3.
Figure 3. Detailed view of the two distinct surfaces on Csk-SH3 involved in peptide recognition. SH3 residues are labeled in green; PEP-3BP1 residues, in orange. a, Polyproline helix recognition surface. The Pro residues on PEP-3BP1 involved in PPII helix formation, Pro 10, Pro 11 and Pro 13, are shown in pink. The important hydrophobic residues, Leu 12 and Thr 16, are shown in green. The charged residue Arg 15, shown in yellow, is involved in charge -charge interaction with Asp 27 in Csk-SH3. The PPII helix sits in the grooves on the Csk-SH3 surface formed mainly by the aromatic residues Tyr 18, Phe 20, Trp 47 and Tyr 64. The PEP-3BP1 residues Pro 10, Leu 12, Pro 13, Arg 15 and Thr 16 are crucial for peptide binding. b, Hydrophobic specificity pocket. The - and -methyls of Ile 21 in PEP-3BP1 'clamp' around the finger formed by Lys 43 of Csk-SH3. The [2]-methyl of Val 22 inserts into a cavity formed by the methyl groups of Ala 40 and Thr 42 on Csk-SH3.

Figure 5.
Figure 5. Comparison of the peptide recognition surfaces in the HIV-1 Nef -Fyn-SH3 (R96I)33 mutant and Csk-SH3 -PEP interactions. Two orientations of the surfaces are shown. The canonical PPII recognition surface is shown in cyan, and the specificity pocket is in red. The PPII recognition pocket is very similar in the two cases, whereas the specificity pockets are quite different. The residues that form the canonical PPII recognition site are labeled in blue. The figures were prepared using GRASP49. The residues that form the specificity pocket in Fyn-SH3 are labeled in brown, and those that form the specificity pocket in Csk-SH3 are labeled in green. a, HIV-1 Nef -Fyn-SH3 (R96I). The residues Ile 96 and Glu 94 form the specificity pocket. Ile 96 provides most of the binding energy to the interaction of the mutant Fyn-SH3 and HIV-1 Nef. Glu 116 corresponds to Lys 43 on Csk-SH3. b, Csk-SH3 -PEP-3BP1. The residues Ala 40, Thr 42 and Lys 43 are deemed crucial for specific recognition of PEP-3BP1. His 21 and Thr 23 correspond to Glu 94 and Ile 96 on Fyn-SH3.

The above figures are reprinted by permission from Macmillan Publishers Ltd: Nat Struct Biol (2001, 8, 998-0) copyright 2001.

Figures were selected by an automated process.