PDBsum entry 1nzv

Transferase

PDB id: 1nzv

Contents

Protein chains

101 a.a. *

103 a.a. *

Ligands

PRO-GLN-PTR-ILE-PTR-VAL-PRO-ALA

PG4

Metals

_CL ×2

Waters ×133

* Residue conservation analysis

PDB id:

1nzv

Name:

Transferase

Title:

Crystal structure of src sh2 domain bound to doubly phosphorylated peptide pqpyipyvpa

Structure:

Tyrosine-protein kinase transforming protein src. Chain: a, b. Fragment: sh2 domain. Synonym: p60-src. Engineered: yes. Doubly phosphorylated peptide pqpyipyvpa. Chain: c. Engineered: yes

Source:

Rous sarcoma virus (strain schmidt-ruppin). Organism_taxid: 11889. Strain: schmidt-ruppin. Gene: v-src. Expressed in: escherichia coli bl21. Expression_system_taxid: 511693. Synthetic: yes

Resolution:

2.10Å R-factor: 0.224 R-free: 0.271

Authors:

O.Y.Lubman,G.Waksman

Key ref:

O.Y.Lubman and G.Waksman (2003). Structural and thermodynamic basis for the interaction of the Src SH2 domain with the activated form of the PDGF beta-receptor. J Mol Biol, 328, 655-668. PubMed id: 12706723 DOI: 10.1016/S0022-2836(03)00344-9

Date:

19-Feb-03 Release date: 22-Apr-03

Protein chain

P00524  (SRC_RSVSA) -  Tyrosine-protein kinase transforming protein Src from Rous sarcoma virus subgroup A (strain Schmidt-Ruppin)

Seq: 526 a.a.

Struc: 101 a.a.

Protein chain

P00524  (SRC_RSVSA) -  Tyrosine-protein kinase transforming protein Src from Rous sarcoma virus subgroup A (strain Schmidt-Ruppin)

Seq: 526 a.a.

Struc: 103 a.a.

Enzyme reactions

• Enzyme class: Chains A, B: 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: 10.1016/S0022-2836(03)00344-9

J Mol Biol 328:655-668 (2003)

PubMed id: 12706723

Structural and thermodynamic basis for the interaction of the Src SH2 domain with the activated form of the PDGF beta-receptor.

O.Y.Lubman, G.Waksman.

ABSTRACT

Recruitment of the Src kinase to the activated form of the platelet-derived growth factor (PDGF) receptor involves recognition of a unique sequence motif in the juxtamembrane region of the receptor by the Src homology 2 (SH2) domain of the enzyme. This motif contains two phosphotyrosine residues separated by one residue (sequence pYIpYV where pY indicates a phosphotyrosine). Here, we provide the thermodynamic and structural basis for the binding of this motif by the Src SH2 domain. We show that the second phosphorylation event increases the free energy window for specific interaction and that the physiological target is exquisitely designed for the task of recruiting specifically an SH2 domain which otherwise demonstrates very little intrinsic ability to discriminate sequences C-terminal to the first phosphorylation event. Surprisingly, we show that water plays a role in the recognition process.

Selected figure(s)

Figure 3.
Figure 3. Details of the interactions between the +1 and +2 pTyr positions and the Src SH2 domain. (A) Stereo-ribbon diagram of the Src SH2 domain bound to the pYEpYI complex.[56.] Side-chains in the SH2 domain that interact with the +1 Glu and +2 pTyr are shown in ball-and stick representation with carbon atoms in dark gray, nitrogen in blue, oxygen in red, and phosphorus in magenta. The corresponding residues are labeled. The peptide is represented as in Figure 1(C) with thicker bonds. Only the +2 pTyr and +1 Glu are labeled. Water molecules are shown as balls, red for those observed in both the bound and unbound forms of the SH2 domain, black for those only observed in the bound form. Water molecules are labeled from 1 to 13 in Figure 3, Figure 4 and Figure 5. (B) Schematic diagram of interactions represented in A between the +1 Glu and +2 pTyr residues and the Src SH2 domain. Residues in the protein are shown in blue while the peptide is in black. Water molecules are labeled as in (A). Contacts are indicated by dotted lines linking the contacting atoms and the distances between contacting atoms are indicated. Red dotted lines indicate contact with water molecules. Black dotted lines indicate direct contacts between peptide and protein.

Figure 5.
Figure 5. Details of the interactions between the -1 Gln and 0-pTyr of the pYEpYI motif and the Src SH2 domain.[56.] Interactions are depicted in a stereo-ribbon diagram in (A) and in a schematic diagram in (B). Representation and labeling are as in Figure 3.

The above figures are reprinted by permission from Elsevier: J Mol Biol (2003, 328, 655-668) copyright 2003.

Figures were selected by an automated process.