3POA

Structural and functional analysis of phosphothreonine-dependent FHA domain interactions


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.01 Å
  • R-Value Free: 0.237 
  • R-Value Work: 0.179 
  • R-Value Observed: 0.182 

wwPDB Validation   3D Report Full Report


This is version 1.1 of the entry. See complete history


Literature

Structural and functional analysis of phosphothreonine-dependent FHA domain interactions

Pennell, S.Westcott, S.Ortiz-Lombardia, M.Patel, D.Li, J.Nott, T.J.Mohammed, D.Buxton, R.S.Yaffe, M.B.Verma, C.Smerdon, S.J.

(2010) Structure 18: 1587-1595

  • DOI: https://doi.org/10.1016/j.str.2010.09.014
  • Primary Citation of Related Structures:  
    3PO8, 3POA

  • PubMed Abstract: 

    FHA domains are well established as phospho-dependent binding modules mediating signal transduction in Ser/Thr kinase signaling networks in both eukaryotic and prokaryotic species. Although they are unique in binding exclusively to phosphothreonine, the basis for this discrimination over phosphoserine has remained elusive. Here, we attempt to dissect overall binding specificity at the molecular level. We first determined the optimal peptide sequence for Rv0020c FHA domain binding by oriented peptide library screening. This served as a basis for systematic mutagenic and binding analyses, allowing us to derive relative thermodynamic contributions of conserved protein and peptide residues to binding and specificity. Structures of phosphopeptide-bound and uncomplexed Rv0020c FHA domain then directed molecular dynamics simulations which show how the extraordinary discrimination in favor of phosphothreonine occurs through formation of additional hydrogen-bonding networks that are ultimately stabilized by van der Waals interactions of the phosphothreonine γ-methyl group with a conserved pocket on the FHA domain surface.


  • Organizational Affiliation

    Division of Molecular Structure, MRC National Institute for Medical Research, The Ridgeway, London NW71AA, UK. spennel@nimr.mrc.ac.uk


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Putative uncharacterized protein TB39.8100Mycobacterium tuberculosisMutation(s): 0 
Gene Names: Rv0020c
UniProt
Find proteins for P71590 (Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv))
Explore P71590 
Go to UniProtKB:  P71590
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP71590
Sequence Annotations
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  • Reference Sequence

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Entity ID: 2
MoleculeChains Sequence LengthOrganismDetailsImage
synthetic phosphopeptide12N/AMutation(s): 0 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
Sequence Annotations
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  • Reference Sequence
Small Molecules
Ligands 1 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
ZN
Query on ZN

Download Ideal Coordinates CCD File 
C [auth A]ZINC ION
Zn
PTFCDOFLOPIGGS-UHFFFAOYSA-N
Modified Residues  1 Unique
IDChains TypeFormula2D DiagramParent
TPO
Query on TPO
B
L-PEPTIDE LINKINGC4 H10 N O6 PTHR
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.01 Å
  • R-Value Free: 0.237 
  • R-Value Work: 0.179 
  • R-Value Observed: 0.182 
  • Space Group: C 2 2 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 57.016α = 90
b = 74.425β = 90
c = 63.016γ = 90
Software Package:
Software NamePurpose
REFMACrefinement

Structure Validation

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Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2011-01-26
    Type: Initial release
  • Version 1.1: 2011-07-13
    Changes: Version format compliance