4D1A

STRUCTURE OF MHP1, A NUCLEOBASE-CATION-SYMPORT-1 FAMILY TRANSPORTER, IN A CLOSED CONFORMATION WITH INDOLYLMETHYL-HYDANTOIN


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 3.40 Å
  • R-Value Free: 0.283 
  • R-Value Work: 0.247 
  • R-Value Observed: 0.249 

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Ligand Structure Quality Assessment 


This is version 1.2 of the entry. See complete history


Literature

Molecular Mechanism of Ligand Recognition by Membrane Transport Protein, Mhp1.

Simmons, K.J.Jackson, S.M.Brueckner, F.Patching, S.G.Beckstein, O.Ivanova, E.Geng, T.Weyand, S.Drew, D.Lanigan, J.Sharples, D.J.Sansom, M.S.Iwata, S.Fishwick, C.W.Johnson, A.P.Cameron, A.D.Henderson, P.J.

(2014) EMBO J 33: 1831

  • DOI: https://doi.org/10.15252/embj.201387557
  • Primary Citation of Related Structures:  
    4D1A, 4D1B, 4D1C, 4D1D

  • PubMed Abstract: 

    The hydantoin transporter Mhp1 is a sodium-coupled secondary active transport protein of the nucleobase-cation-symport family and a member of the widespread 5-helix inverted repeat superfamily of transporters. The structure of Mhp1 was previously solved in three different conformations providing insight into the molecular basis of the alternating access mechanism. Here, we elucidate detailed events of substrate binding, through a combination of crystallography, molecular dynamics, site-directed mutagenesis, biochemical/biophysical assays, and the design and synthesis of novel ligands. We show precisely where 5-substituted hydantoin substrates bind in an extended configuration at the interface of the bundle and hash domains. They are recognised through hydrogen bonds to the hydantoin moiety and the complementarity of the 5-substituent for a hydrophobic pocket in the protein. Furthermore, we describe a novel structure of an intermediate state of the protein with the external thin gate locked open by an inhibitor, 5-(2-naphthylmethyl)-L-hydantoin, which becomes a substrate when leucine 363 is changed to an alanine. We deduce the molecular events that underlie acquisition and transport of a ligand by Mhp1.


  • Organizational Affiliation

    School of Chemistry and Astbury Centre for Structural Molecular Biology, University of Leeds, Leeds, UK.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
HYDANTOIN TRANSPORT PROTEIN495Microbacterium liquefaciensMutation(s): 0 
Membrane Entity: Yes 
UniProt
Find proteins for D6R8X8 (Microbacterium liquefaciens)
Explore D6R8X8 
Go to UniProtKB:  D6R8X8
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupD6R8X8
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 2 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
I5H
Query on I5H

Download Ideal Coordinates CCD File 
B [auth A](5S)-5-(1H-indol-3-ylmethyl)imidazolidine-2,4-dione
C12 H11 N3 O2
RUUREKIGAKIKIL-JTQLQIEISA-N
NA
Query on NA

Download Ideal Coordinates CCD File 
C [auth A]SODIUM ION
Na
FKNQFGJONOIPTF-UHFFFAOYSA-N
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 3.40 Å
  • R-Value Free: 0.283 
  • R-Value Work: 0.247 
  • R-Value Observed: 0.249 
  • Space Group: P 21 21 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 87.43α = 90
b = 106.36β = 90
c = 100.55γ = 90
Software Package:
Software NamePurpose
PHENIXrefinement
XDSdata reduction
XSCALEdata scaling
PHASERphasing

Structure Validation

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Ligand Structure Quality Assessment 


Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2014-07-02
    Type: Initial release
  • Version 1.1: 2014-08-20
    Changes: Database references
  • Version 1.2: 2023-12-20
    Changes: Data collection, Database references, Derived calculations, Other, Refinement description