1E3W

Rat brain 3-hydroxyacyl-CoA dehydrogenase binary complex with NADH and 3-keto butyrate


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.00 Å
  • R-Value Free: 0.226 
  • R-Value Work: 0.189 

wwPDB Validation   3D Report Full Report


This is version 1.6 of the entry. See complete history


Literature

Recognition of Structurally Diverse Substrates by Type II 3-Hydroxyacyl-Coa Dehydrogenase (Hadh II) Amyloid-Beta Binding Alcohol Dehydrogenase (Abad)

Powell, A.J.Read, J.A.Banfield, M.J.Gunn-Moore, F.Yan, S.D.Lustbader, J.Stern, A.R.Stern, D.M.Brady, R.L.

(2000) J Mol Biol 303: 311

  • DOI: https://doi.org/10.1006/jmbi.2000.4139
  • Primary Citation of Related Structures:  
    1E3S, 1E3W, 1E6W

  • PubMed Abstract: 

    Human type II hydroxyacyl-CoA dehydrogenase/amyloid-beta binding alcohol dehydrogenase (HADH II/ABAD) is an oxidoreductase whose salient features include broad substrate specificity, encompassing 3-hydroxyacyl-CoA derivatives, hydroxysteroids, alcohols and beta-hydroxybutyrate, and the capacity to bind amyloid-beta peptide, leading to propagation of amyloid-induced cell stress. In this study, we examine the structure and enzymatic activity of the homologous rat HADH II/ABAD enzyme. We report the crystal structure of rat HADH II/ABAD as a binary complex with its NADH cofactor to 2.0 A resolution, as a ternary complex with NAD(+) and 3-ketobutyrate (acetoacetate) to 1.4 A resolution, and as a ternary complex with NADH and 17 beta-estradiol to 1.7 A resolution. This first crystal structure of an HADH II confirms these enzymes are closely related to the short-chain hydroxysteroid dehydrogenases and differ substantially from the classic, type I 3-hydroxyacyl-CoA dehydrogenases. Binding of the ketobutyrate substrate is accompanied by closure of the active site specificity loop, whereas the steroid substrate does not appear to require closure for binding. Despite the different chemical nature of the two bound substrates, the presentation of chemical groups within the active site of each complex is remarkably similar, allowing a general mechanism for catalytic activity to be proposed. There is a characteristic extension to the active site that is likely to accommodate the CoA moiety of 3-hydroxyacyl-CoA substrates. Rat HADH II/ABAD also binds amyloid-beta (1-40) peptide with a K(D) of 21 nM, which is similar to the interaction exhibited between this peptide and human HADH II/ABAD. These studies provide the first structural insights into HADH II/ABAD interaction with its substrates, and indicate the relevance of the rodent enzyme and associated rodent models for analysis of HADH II/ABAD's physiologic and pathophysiologic properties.


  • Organizational Affiliation

    Department of Biochemistry, University of Bristol, Bristol, UK.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
SHORT CHAIN 3-HYDROXYACYL-COA DEHYDROGENASE261Rattus norvegicusMutation(s): 0 
EC: 1.1.1.35
UniProt
Find proteins for O70351 (Rattus norvegicus)
Explore O70351 
Go to UniProtKB:  O70351
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupO70351
Sequence Annotations
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  • Reference Sequence
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 2
MoleculeChains Sequence LengthOrganismDetailsImage
SHORT CHAIN 3-HYDROXYACYL-COA DEHYDROGENASE
B, C, D
261Rattus norvegicusMutation(s): 0 
EC: 1.1.1.35
UniProt
Find proteins for O70351 (Rattus norvegicus)
Explore O70351 
Go to UniProtKB:  O70351
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupO70351
Sequence Annotations
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  • Reference Sequence
Small Molecules
Ligands 4 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
NAD
Query on NAD

Download Ideal Coordinates CCD File 
E [auth A],
I [auth B],
L [auth C],
O [auth D]
NICOTINAMIDE-ADENINE-DINUCLEOTIDE
C21 H27 N7 O14 P2
BAWFJGJZGIEFAR-NNYOXOHSSA-N
TRS
Query on TRS

Download Ideal Coordinates CCD File 
F [auth A],
J [auth B],
N [auth C]
2-AMINO-2-HYDROXYMETHYL-PROPANE-1,3-DIOL
C4 H12 N O3
LENZDBCJOHFCAS-UHFFFAOYSA-O
AAE
Query on AAE

Download Ideal Coordinates CCD File 
P [auth D]ACETOACETIC ACID
C4 H6 O3
WDJHALXBUFZDSR-UHFFFAOYSA-N
SO4
Query on SO4

Download Ideal Coordinates CCD File 
G [auth A],
H [auth A],
K [auth B],
M [auth C],
Q [auth D]
SULFATE ION
O4 S
QAOWNCQODCNURD-UHFFFAOYSA-L
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.00 Å
  • R-Value Free: 0.226 
  • R-Value Work: 0.189 
  • Space Group: P 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 57.603α = 65.22
b = 67.426β = 73.27
c = 67.5γ = 75.67
Software Package:
Software NamePurpose
REFMACrefinement
DENZOdata reduction
SCALEPACKdata scaling
AMoREphasing

Structure Validation

View Full Validation Report



Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2001-05-25
    Type: Initial release
  • Version 1.1: 2011-05-08
    Changes: Version format compliance
  • Version 1.2: 2011-07-13
    Changes: Version format compliance
  • Version 1.3: 2017-07-12
    Changes: Derived calculations
  • Version 1.4: 2019-05-08
    Changes: Data collection, Derived calculations, Experimental preparation
  • Version 1.5: 2019-07-24
    Changes: Data collection
  • Version 1.6: 2023-12-13
    Changes: Advisory, Data collection, Database references, Derived calculations, Refinement description