6SBV

X-ray Structure of Human LDH-A with an Allosteric Inhibitor (Compound 7)


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.60 Å
  • R-Value Free: 0.242 
  • R-Value Work: 0.219 
  • R-Value Observed: 0.220 

wwPDB Validation   3D Report Full Report


Ligand Structure Quality Assessment 


This is version 1.2 of the entry. See complete history


Literature

Structural Evidence for Isoform-Selective Allosteric Inhibition of Lactate Dehydrogenase A.

Friberg, A.Rehwinkel, H.Nguyen, D.Putter, V.Quanz, M.Weiske, J.Eberspacher, U.Heisler, I.Langer, G.

(2020) ACS Omega 5: 13034-13041

  • DOI: https://doi.org/10.1021/acsomega.0c00715
  • Primary Citation of Related Structures:  
    6SBU, 6SBV

  • PubMed Abstract: 

    Lactate dehydrogenase A (LDHA) is frequently overexpressed in tumors, thereby sustaining high glycolysis rates, tumor growth, and chemoresistance. High-throughput screening resulted in the identification of phthalimide and dibenzofuran derivatives as novel lactate dehydrogenase inhibitors, selectively inhibiting the activity of the LDHA isoenzyme. Cocrystallization experiments confirmed target engagement in addition to demonstrating binding to a novel allosteric binding site present in all four LDHA subunits of the LDH5 homotetramer.


  • Organizational Affiliation

    Bayer AG, Pharmaceuticals, R&D, Müllerstrasse 178, 13342 Berlin, Germany.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
L-lactate dehydrogenase A chain
A, B, C, D, E
A, B, C, D, E, F, G, H
332Homo sapiensMutation(s): 0 
Gene Names: LDHAPIG19
EC: 1.1.1.27
UniProt & NIH Common Fund Data Resources
Find proteins for P00338 (Homo sapiens)
Explore P00338 
Go to UniProtKB:  P00338
PHAROS:  P00338
GTEx:  ENSG00000134333 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP00338
Sequence Annotations
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  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.60 Å
  • R-Value Free: 0.242 
  • R-Value Work: 0.219 
  • R-Value Observed: 0.220 
  • Space Group: P 21 21 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 80.369α = 90
b = 146.287β = 90
c = 308.362γ = 90
Software Package:
Software NamePurpose
REFMACrefinement
XDSdata reduction
XSCALEdata scaling
PHASERphasing
Cootmodel building

Structure Validation

View Full Validation Report



Ligand Structure Quality Assessment 


Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2020-06-10
    Type: Initial release
  • Version 1.1: 2020-07-01
    Changes: Database references
  • Version 1.2: 2024-01-24
    Changes: Advisory, Data collection, Database references, Refinement description