6BAU

Crystal Structure of GltPh R397C in complex with L-Cysteine


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 3.80 Å
  • R-Value Free: 0.290 
  • R-Value Work: 0.267 
  • R-Value Observed: 0.268 

wwPDB Validation   3D Report Full Report


This is version 1.2 of the entry. See complete history


Literature

Structural characterisation reveals insights into substrate recognition by the glutamine transporter ASCT2/SLC1A5.

Scopelliti, A.J.Font, J.Vandenberg, R.J.Boudker, O.Ryan, R.M.

(2018) Nat Commun 9: 38-38

  • DOI: https://doi.org/10.1038/s41467-017-02444-w
  • Primary Citation of Related Structures:  
    6BAT, 6BAU, 6BAV, 6BMI

  • PubMed Abstract: 

    Cancer cells undergo a shift in metabolism where they become reliant on nutrients such as the amino-acid glutamine. Glutamine enters the cell via the alanine/serine/cysteine transporter 2 (ASCT2) that is upregulated in several cancers to maintain an increased supply of this nutrient and are therefore an attractive target in cancer therapeutic development. ASCT2 belongs to the glutamate transporter (SLC1A) family but is the only transporter in this family able to transport glutamine. The structural basis for glutamine selectivity of ASCT2 is unknown. Here, we identify two amino-acid residues in the substrate-binding site that are responsible for conferring glutamine selectivity. We introduce corresponding mutations into a prokaryotic homologue of ASCT2 and solve four crystal structures, which reveal the structural basis for neutral amino acid and inhibitor binding in this family. This structural model of ASCT2 may provide a basis for future development of selective ASCT2 inhibitors to treat glutamine-dependent cancers.


  • Organizational Affiliation

    Transporter Biology Group, Discipline of Pharmacology, Sydney Medical School, University of Sydney, Sydney, NSW, 2006, Australia.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Glutamate transporter homolog
A, B, C
420Pyrococcus horikoshii OT3Mutation(s): 1 
Gene Names: PH1295
Membrane Entity: Yes 
UniProt
Find proteins for O59010 (Pyrococcus horikoshii (strain ATCC 700860 / DSM 12428 / JCM 9974 / NBRC 100139 / OT-3))
Explore O59010 
Go to UniProtKB:  O59010
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupO59010
Sequence Annotations
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  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 3.80 Å
  • R-Value Free: 0.290 
  • R-Value Work: 0.267 
  • R-Value Observed: 0.268 
  • Space Group: P 61
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 115.313α = 90
b = 115.313β = 90
c = 322.274γ = 120
Software Package:
Software NamePurpose
SCALAdata scaling
REFMACrefinement
PDB_EXTRACTdata extraction
XDSdata reduction
PHASERphasing

Structure Validation

View Full Validation Report



Entry History & Funding Information

Deposition Data


Funding OrganizationLocationGrant Number
National Health and Medical Research Council (NHMRC, Australia)AustraliaAPP1048784
National Institutes of Health/National Institute of Neurological Disorders and Stroke (NIH/NINDS)United StatesR01NS064357

Revision History  (Full details and data files)

  • Version 1.0: 2018-01-17
    Type: Initial release
  • Version 1.1: 2019-12-18
    Changes: Author supporting evidence
  • Version 1.2: 2023-10-04
    Changes: Data collection, Database references, Refinement description