PDBsum entry: 1fhq

Transferase

PDB id: 1fhq

Contents

Protein chain

158 a.a. *

* Residue conservation analysis

PDB id:

1fhq

Name:

Transferase

Title:

Refined solution structure of the fha2 domain of rad53

Structure:

Protein kinase spk1. Chain: a. Fragment: c-terminal fha domain (fha2). Engineered: yes

Source:

Saccharomyces cerevisiae. Baker's yeast. Organism_taxid: 4932. Expressed in: escherichia coli. Expression_system_taxid: 562.

NMR struc:

20 models

Authors:

I.-J.L.Byeon,H.Liao,M.-D.Tsai

Key ref:

P.Wang et al. (2000). II. Structure and specificity of the interaction between the FHA2 domain of Rad53 and phosphotyrosyl peptides. J Mol Biol, 302, 927-940. PubMed id: 10993733 DOI: 10.1006/jmbi.2000.4095

Date:

02-Aug-00 Release date: 18-Oct-00

Protein chain

P22216  (RAD53_YEAST) -  Serine/threonine-protein kinase RAD53

Seq: 821 a.a.

Struc: 158 a.a.

Enzyme reactions

• Enzyme class: E.C.2.7.11.1 - Non-specific serine/threonine protein kinase.
• Reaction: ATP + a protein = ADP + a phosphoprotein

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

reference

DOI no: 10.1006/jmbi.2000.4095

J Mol Biol 302:927-940 (2000)

PubMed id: 10993733

II. Structure and specificity of the interaction between the FHA2 domain of Rad53 and phosphotyrosyl peptides.

P.Wang, I.J.Byeon, H.Liao, K.D.Beebe, S.Yongkiettrakul, D.Pei, M.D.Tsai.

ABSTRACT

The forkhead-associated (FHA) domain is a protein module found in many proteins involved in cell signaling in response to DNA damage. It has been suggested to bind to pThr sites of its target protein. Recently we have determined the first structure of an FHA domain, FHA2 from the yeast protein Rad53, and demonstrated that FHA2 binds to a pTyr-containing peptide (826)EDI(pY)YLD(832) from Rad9, with a moderate affinity (K(d) ca. 100 microM). We now report the solution structure of the complex of FHA2 bound with this pTyr peptide. The structure shows that the phosphate group of pTyr interacts directly with three arginine residues (605, 617, and 620), and that the leucine residue at the +2 position from the pTyr interacts with a hydrophobic surface on FHA2. The sequence specificity of FHA2 was determined by screening a combinatorial pTyr library. The results clearly show that FHA2 recognizes specific sequences C-terminal to pTyr with the following consensus: XX(pY)N(1)N(2)N(3), where N(1)=Leu, Met, Phe, or Ile, N(2)=Tyr, Phe, Leu, or Met, and N(3)=Phe, Leu, or Met. Two of the selected peptides, GF(pY)LYFIR and DV(pY)FYMIR, bind FHA2 with K(d) values of 1.1 and 5.0 microM, respectively. The results, along with other recent reports, demonstrate that the FHA domain is a new class of phosphoprotein-binding domain, capable of binding both pTyr and pThr sequences.

Selected figure(s)

Figure 5.
Figure 5. The binding interface for FHA2 and the Rad9 pTyr peptide (a) Surface representation of the FHA2 domain in complex with the peptide; (b) side-chain interactions of the peptide with the FHA2 domain. The backbone ribbons of FHA2 and the peptide are shown in purple and green, respectively. The side-chains of FHA2 and the peptide are shown in red and yellow, respectively. MOLMOL [Koradi et al 1996] and Insight II (Molecular Simulations Inc.) were used for (a) and (b), respectively.

Figure 6.
Figure 6. Schematic ribbon diagrams of the FHA2-Rad9 pTyr peptide and the SH2-pTyr peptide [Eck et al 1993] complex structures. The pTyr binding sites are also shown. The Figure was generated using MOLSCRIPT [Kraulis 1991].

The above figures are reprinted by permission from Elsevier: J Mol Biol (2000, 302, 927-940) copyright 2000.

Figures were selected by an automated process.