4FC7

Studies on DCR shed new light on peroxisomal beta-oxidation: Crystal structure of the ternary complex of pDCR


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.84 Å
  • R-Value Free: 0.209 
  • R-Value Work: 0.167 
  • R-Value Observed: 0.169 

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Ligand Structure Quality Assessment 


This is version 1.3 of the entry. See complete history


Literature

Studies of human 2,4-dienoyl CoA reductase shed new light on peroxisomal beta-oxidation of unsaturated fatty acids

Hua, T.Wu, D.Ding, W.Wang, J.Shaw, N.Liu, Z.J.

(2012) J Biol Chem 287: 28956-28965

  • DOI: https://doi.org/10.1074/jbc.M112.385351
  • Primary Citation of Related Structures:  
    4FC6, 4FC7

  • PubMed Abstract: 

    Peroxisomes play an essential role in maintaining fatty acid homeostasis. Although mitochondria are also known to participate in the catabolism of fatty acids via β-oxidation, differences exist between the peroxisomal and mitochondrial β-oxidation. Only peroxisomes, but not mitochondrion, can shorten very long chain fatty acids. Here, we describe the crystal structure of a ternary complex of peroxisomal 2,4-dienoyl CoA reductases (pDCR) with hexadienoyl CoA and NADP, as a prototype for comparison with the mitochondrial 2,4-dienoyl CoA reductase (mDCR) to shed light on the differences between the enzymes from the two organelles at the molecular level. Unexpectedly, the structure of pDCR refined to 1.84 Å resolution reveals the absence of the tyrosine-serine pair seen in the active site of mDCR, which together with a lysine and an asparagine have been deemed a hallmark of the SDR family of enzymes. Instead, aspartate hydrogen-bonded to the Cα hydroxyl via a water molecule seems to perturb the water molecule for protonation of the substrate. Our studies provide the first structural evidence for participation of water in the DCR-catalyzed reactions. Biochemical studies and structural analysis suggest that pDCRs can catalyze the shortening of six-carbon-long substrates in vitro. However, the K(m) values of pDCR for short chain acyl CoAs are at least 6-fold higher than those for substrates with 10 or more aliphatic carbons. Unlike mDCR, hinge movements permit pDCR to process very long chain polyunsaturated fatty acids.


  • Organizational Affiliation

    National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Peroxisomal 2,4-dienoyl-CoA reductase
A, B, C, D
277Homo sapiensMutation(s): 0 
Gene Names: DECR2PDCR
EC: 1.3.1.34 (PDB Primary Data), 1.3.1.124 (UniProt)
UniProt & NIH Common Fund Data Resources
Find proteins for Q9NUI1 (Homo sapiens)
Explore Q9NUI1 
Go to UniProtKB:  Q9NUI1
PHAROS:  Q9NUI1
GTEx:  ENSG00000242612 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ9NUI1
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 2 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
COA
Query on COA

Download Ideal Coordinates CCD File 
F [auth A],
H [auth B],
J [auth C],
L [auth D]
COENZYME A
C21 H36 N7 O16 P3 S
RGJOEKWQDUBAIZ-IBOSZNHHSA-N
NAP
Query on NAP

Download Ideal Coordinates CCD File 
E [auth A],
G [auth B],
I [auth C],
K [auth D]
NADP NICOTINAMIDE-ADENINE-DINUCLEOTIDE PHOSPHATE
C21 H28 N7 O17 P3
XJLXINKUBYWONI-NNYOXOHSSA-N
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.84 Å
  • R-Value Free: 0.209 
  • R-Value Work: 0.167 
  • R-Value Observed: 0.169 
  • Space Group: P 21 21 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 88.1α = 90
b = 94.502β = 90
c = 130.156γ = 90
Software Package:
Software NamePurpose
HKL-2000data collection
PHASESphasing
REFMACrefinement
HKL-2000data reduction
HKL-2000data scaling

Structure Validation

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Ligand Structure Quality Assessment 


Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2012-07-04
    Type: Initial release
  • Version 1.1: 2012-07-11
    Changes: Database references
  • Version 1.2: 2013-07-24
    Changes: Database references
  • Version 1.3: 2024-02-28
    Changes: Data collection, Database references, Derived calculations