1ZUM

Human Mitochondrial Aldehyde Dehydrogenase Asian Variant, ALDH2*2, Apo Form


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.10 Å
  • R-Value Free: 0.238 
  • R-Value Work: 0.204 
  • R-Value Observed: 0.204 

wwPDB Validation   3D Report Full Report


This is version 1.5 of the entry. See complete history


Literature

Disruption of the coenzyme binding site and dimer interface revealed in the crystal structure of mitochondrial aldehyde dehydrogenase "asian" variant

Larson, H.N.Weiner, H.Hurley, T.D.

(2005) J Biol Chem 280: 30550-30556

  • DOI: https://doi.org/10.1074/jbc.M502345200
  • Primary Citation of Related Structures:  
    1ZUM

  • PubMed Abstract: 

    Mitochondrial aldehyde dehydrogenase (ALDH2) is the major enzyme that oxidizes ethanol-derived acetaldehyde. A nearly inactive form of the enzyme, ALDH2*2, is found in about 40% of the East Asian population. This variant enzyme is defined by a glutamate to lysine substitution at residue 487 located within the oligomerization domain. ALDH2*2 has an increased Km for its coenzyme, NAD+, and a decreased kcat, which lead to low activity in vivo. Here we report the 2.1 A crystal structure of ALDH2*2. The structure shows a large disordered region located at the dimer interface that includes much of the coenzyme binding cleft and a loop of residues that form the base of the active site. As a consequence of these structural changes, the variant enzyme exhibits rigid body rotations of its catalytic and coenzyme-binding domains relative to the oligomerization domain. These structural perturbations are the direct result of the inability of lysine 487 to form important stabilizing hydrogen bonds with arginines 264 and 475. Thus, the elevated Km for coenzyme exhibited by this variant probably reflects the energetic penalty for reestablishing this site for productive coenzyme binding, whereas the structural alterations near the active site are consistent with the lowered Vmax.


  • Organizational Affiliation

    Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, Indiana 46202, USA.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Aldehyde dehydrogenase
A, B, C, D, E
A, B, C, D, E, F, G, H, I, J, K, L
500Homo sapiensMutation(s): 1 
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 3 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
EDO
Query on EDO

Download Ideal Coordinates CCD File 
AA [auth D]
AB [auth L]
DA [auth E]
HA [auth F]
IA [auth F]
AA [auth D],
AB [auth L],
DA [auth E],
HA [auth F],
IA [auth F],
JA [auth F],
MA [auth G],
NA [auth G],
O [auth A],
OA [auth G],
P [auth A],
Q [auth A],
R [auth A],
T [auth B],
TA [auth I],
UA [auth I],
V [auth C],
W [auth C],
WA [auth J],
X [auth C],
Z [auth D]
1,2-ETHANEDIOL
C2 H6 O2
LYCAIKOWRPUZTN-UHFFFAOYSA-N
GAI
Query on GAI

Download Ideal Coordinates CCD File 
CA [auth E]
FA [auth F]
GA [auth F]
LA [auth G]
N [auth A]
CA [auth E],
FA [auth F],
GA [auth F],
LA [auth G],
N [auth A],
QA [auth H],
SA [auth I],
ZA [auth L]
GUANIDINE
C H5 N3
ZRALSGWEFCBTJO-UHFFFAOYSA-N
NA
Query on NA

Download Ideal Coordinates CCD File 
BA [auth E]
EA [auth F]
KA [auth G]
M [auth A]
PA [auth H]
BA [auth E],
EA [auth F],
KA [auth G],
M [auth A],
PA [auth H],
RA [auth I],
S [auth B],
U [auth C],
VA [auth J],
XA [auth K],
Y [auth D],
YA [auth L]
SODIUM ION
Na
FKNQFGJONOIPTF-UHFFFAOYSA-N
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.10 Å
  • R-Value Free: 0.238 
  • R-Value Work: 0.204 
  • R-Value Observed: 0.204 
  • Space Group: P 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 95.873α = 78.81
b = 105.261β = 81.95
c = 162.672γ = 88.04
Software Package:
Software NamePurpose
CNSrefinement
HKL-2000data reduction
SCALEPACKdata scaling
AMoREphasing

Structure Validation

View Full Validation Report



Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2005-06-28
    Type: Initial release
  • Version 1.1: 2008-04-30
    Changes: Version format compliance
  • Version 1.2: 2011-07-13
    Changes: Version format compliance
  • Version 1.3: 2014-11-12
    Changes: Structure summary
  • Version 1.4: 2021-10-20
    Changes: Database references, Derived calculations
  • Version 1.5: 2023-08-23
    Changes: Data collection, Refinement description