1RX0

Crystal structure of isobutyryl-CoA dehydrogenase complexed with substrate/ligand.


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.77 Å
  • R-Value Free: 0.192 
  • R-Value Work: 0.179 
  • R-Value Observed: 0.179 

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Ligand Structure Quality Assessment 


This is version 1.4 of the entry. See complete history


Literature

Structures of Isobutyryl-CoA Dehydrogenase and Enzyme-Product Complex: COMPARISON WITH ISOVALERYL- AND SHORT-CHAIN ACYL-COA DEHYDROGENASES.

Battaile, K.P.Nguyen, T.V.Vockley, J.Kim, J.J.

(2004) J Biol Chem 279: 16526-16534

  • DOI: https://doi.org/10.1074/jbc.M400034200
  • Primary Citation of Related Structures:  
    1RX0

  • PubMed Abstract: 

    The acyl-CoA dehydrogenases are a family of mitochondrial flavoproteins involved in the catabolism of fatty and amino acids. Isobutyryl-CoA dehydrogenase (IBD) is involved in the catabolism of valine and catalyzes the conversion of isobutyryl-CoA to methacrylyl-CoA. The crystal structure of IBD with and without substrate has been determined to 1.76-A resolution. The asymmetric unit contains a homotetramer with substrate/product bound in two monomers. The overall structure of IBD is similar to those of previously determined acyl-CoA dehydrogenases and consists of an NH2-terminal alpha-helical domain, a medial beta-strand domain and a C-terminal alpha-helical domain. The enzyme-bound ligand has been modeled in as the reaction product, methacrylyl-CoA. The location of Glu-376 with respect to the C-2-C-3 of the bound product and FAD confirms Glu-376 to be the catalytic base. IBD has a shorter and wider substrate-binding cavity relative to short-chain acyl-CoA dehydrogenase, permitting the optimal binding of the isobutyryl-CoA substrate. The dramatic lateral expansion of the binding cavity seen in isovaleryl-CoA dehydrogenase is not observed in IBD. The conserved tyrosine or phenylalanine that defines a side of the binding cavity in other acyl-CoA dehydrogenases is replaced by a leucine (Leu-375) in the current structure. Substrate binding changes the position of some residues lining the binding pocket as well as the position of the loop containing the catalytic glutamate and subsequent helix. Three clinical mutations have been modeled to the structure. The mutations do not affect substrate binding but instead appear to disrupt protein folding and/or stability.


  • Organizational Affiliation

    Department of Biochemistry, Medical College of Wisconsin, Milwaukee, Wisconsin 53226, USA.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Acyl-CoA dehydrogenase family member 8, mitochondrial
A, B, C, D
393Homo sapiensMutation(s): 0 
Gene Names: ACAD8ARC42
EC: 1.3.99
UniProt & NIH Common Fund Data Resources
Find proteins for Q9UKU7 (Homo sapiens)
Explore Q9UKU7 
Go to UniProtKB:  Q9UKU7
PHAROS:  Q9UKU7
GTEx:  ENSG00000151498 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ9UKU7
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 4 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
2MC
Query on 2MC

Download Ideal Coordinates CCD File 
T [auth C],
Y [auth D]
METHACRYLYL-COENZYME A
C25 H40 N7 O17 P3 S
NPALUEYCDZWBOV-NDZSKPAWSA-N
FAD
Query on FAD

Download Ideal Coordinates CCD File 
G [auth A],
M [auth B],
S [auth C],
X [auth D]
FLAVIN-ADENINE DINUCLEOTIDE
C27 H33 N9 O15 P2
VWWQXMAJTJZDQX-UYBVJOGSSA-N
EDO
Query on EDO

Download Ideal Coordinates CCD File 
E [auth A]
F [auth A]
I [auth B]
J [auth B]
K [auth B]
E [auth A],
F [auth A],
I [auth B],
J [auth B],
K [auth B],
L [auth B],
P [auth C],
Q [auth C],
R [auth C],
V [auth D],
W [auth D]
1,2-ETHANEDIOL
C2 H6 O2
LYCAIKOWRPUZTN-UHFFFAOYSA-N
ACY
Query on ACY

Download Ideal Coordinates CCD File 
AA [auth D]
BA [auth D]
H [auth A]
N [auth B]
O [auth B]
AA [auth D],
BA [auth D],
H [auth A],
N [auth B],
O [auth B],
U [auth C],
Z [auth D]
ACETIC ACID
C2 H4 O2
QTBSBXVTEAMEQO-UHFFFAOYSA-N
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.77 Å
  • R-Value Free: 0.192 
  • R-Value Work: 0.179 
  • R-Value Observed: 0.179 
  • Space Group: P 21 21 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 97.204α = 90
b = 134.343β = 90
c = 189.641γ = 90
Software Package:
Software NamePurpose
CNSrefinement
DENZOdata reduction
SCALEPACKdata scaling
CNSphasing

Structure Validation

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Ligand Structure Quality Assessment 


Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2004-04-20
    Type: Initial release
  • Version 1.1: 2008-04-29
    Changes: Version format compliance
  • Version 1.2: 2011-07-13
    Changes: Version format compliance
  • Version 1.3: 2018-01-31
    Changes: Experimental preparation
  • Version 1.4: 2024-02-14
    Changes: Data collection, Database references, Derived calculations