3INJ

Human Mitochondrial Aldehyde Dehydrogenase complexed with agonist Alda-1


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.69 Å
  • R-Value Free: 0.200 
  • R-Value Work: 0.179 
  • R-Value Observed: 0.180 

wwPDB Validation   3D Report Full Report


Ligand Structure Quality Assessment 


This is version 1.2 of the entry. See complete history


Literature

Alda-1 is an agonist and chemical chaperone for the common human aldehyde dehydrogenase 2 variant.

Perez-Miller, S.Younus, H.Vanam, R.Chen, C.H.Mochly-Rosen, D.Hurley, T.D.

(2010) Nat Struct Mol Biol 17: 159-164

  • DOI: https://doi.org/10.1038/nsmb.1737
  • Primary Citation of Related Structures:  
    3INJ, 3INL

  • PubMed Abstract: 

    In approximately one billion people, a point mutation inactivates a key detoxifying enzyme, aldehyde dehydrogenase (ALDH2). This mitochondrial enzyme metabolizes toxic biogenic and environmental aldehydes, including the endogenously produced 4-hydroxynonenal (4HNE) and the environmental pollutant acrolein, and also bioactivates nitroglycerin. ALDH2 is best known, however, for its role in ethanol metabolism. The accumulation of acetaldehyde following the consumption of even a single alcoholic beverage leads to the Asian alcohol-induced flushing syndrome in ALDH2*2 homozygotes. The ALDH2*2 allele is semidominant, and heterozygotic individuals show a similar but less severe phenotype. We recently identified a small molecule, Alda-1, that activates wild-type ALDH2 and restores near-wild-type activity to ALDH2*2. The structures of Alda-1 bound to ALDH2 and ALDH2*2 reveal how Alda-1 activates the wild-type enzyme and how it restores the activity of ALDH2*2 by acting as a structural chaperone.


  • Organizational Affiliation

    Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, Indiana, USA.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Aldehyde dehydrogenase, mitochondrial
A, B, C, D, E
A, B, C, D, E, F, G, H
500Homo sapiensMutation(s): 0 
Gene Names: ALDH2ALDM
EC: 1.2.1.3
UniProt & NIH Common Fund Data Resources
Find proteins for P05091 (Homo sapiens)
Explore P05091 
Go to UniProtKB:  P05091
PHAROS:  P05091
GTEx:  ENSG00000111275 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP05091
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 4 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
BXB
Query on BXB

Download Ideal Coordinates CCD File 
CA [auth D]
HA [auth E]
M [auth A]
MA [auth F]
S [auth B]
CA [auth D],
HA [auth E],
M [auth A],
MA [auth F],
S [auth B],
SA [auth G],
WA [auth H],
X [auth C]
N-(1,3-benzodioxol-5-ylmethyl)-2,6-dichlorobenzamide
C15 H11 Cl2 N O3
NMKJFZCBCIUYHI-UHFFFAOYSA-N
EDO
Query on EDO

Download Ideal Coordinates CCD File 
AA [auth D]
EA [auth E]
FA [auth E]
IA [auth E]
J [auth A]
AA [auth D],
EA [auth E],
FA [auth E],
IA [auth E],
J [auth A],
K [auth A],
KA [auth F],
N [auth A],
NA [auth F],
P [auth B],
PA [auth G],
Q [auth B],
T [auth B],
UA [auth H],
V [auth C],
Y [auth D]
1,2-ETHANEDIOL
C2 H6 O2
LYCAIKOWRPUZTN-UHFFFAOYSA-N
GAI
Query on GAI

Download Ideal Coordinates CCD File 
BA [auth D]
GA [auth E]
L [auth A]
LA [auth F]
QA [auth G]
BA [auth D],
GA [auth E],
L [auth A],
LA [auth F],
QA [auth G],
R [auth B],
RA [auth G],
VA [auth H],
W [auth C]
GUANIDINE
C H5 N3
ZRALSGWEFCBTJO-UHFFFAOYSA-N
NA
Query on NA

Download Ideal Coordinates CCD File 
DA [auth E]
I [auth A]
JA [auth F]
O [auth B]
OA [auth G]
DA [auth E],
I [auth A],
JA [auth F],
O [auth B],
OA [auth G],
TA [auth H],
U [auth C],
Z [auth D]
SODIUM ION
Na
FKNQFGJONOIPTF-UHFFFAOYSA-N
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.69 Å
  • R-Value Free: 0.200 
  • R-Value Work: 0.179 
  • R-Value Observed: 0.180 
  • Space Group: P 1 21 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 101.916α = 90
b = 176.839β = 94.52
c = 102.464γ = 90
Software Package:
Software NamePurpose
DENZOdata reduction
SCALEPACKdata scaling
AMoREphasing
PHENIXrefinement
PDB_EXTRACTdata extraction
HKL-2000data collection
HKL-2000data reduction
HKL-2000data scaling

Structure Validation

View Full Validation Report



Ligand Structure Quality Assessment 


Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2010-01-12
    Type: Initial release
  • Version 1.1: 2011-07-13
    Changes: Version format compliance
  • Version 1.2: 2017-11-01
    Changes: Refinement description