2HDH

BIOCHEMICAL CHARACTERIZATION AND STRUCTURE DETERMINATION OF HUMAN HEART SHORT CHAIN L-3-HYDROXYACYL COA DEHYDROGENASE PROVIDE INSIGHT INTO CATALYTIC MECHANISM


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.20 Å
  • R-Value Free: 0.251 
  • R-Value Work: 0.198 

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Ligand Structure Quality Assessment 


This is version 1.3 of the entry. See complete history


Literature

Biochemical characterization and crystal structure determination of human heart short chain L-3-hydroxyacyl-CoA dehydrogenase provide insights into catalytic mechanism.

Barycki, J.J.O'Brien, L.K.Bratt, J.M.Zhang, R.Sanishvili, R.Strauss, A.W.Banaszak, L.J.

(1999) Biochemistry 38: 5786-5798

  • DOI: https://doi.org/10.1021/bi9829027
  • Primary Citation of Related Structures:  
    2HDH, 3HAD

  • PubMed Abstract: 

    Human heart short chain L-3-hydroxyacyl-CoA dehydrogenase (SCHAD) catalyzes the oxidation of the hydroxyl group of L-3-hydroxyacyl-CoA to a keto group, concomitant with the reduction of NAD+ to NADH, as part of the beta-oxidation pathway. The homodimeric enzyme has been overexpressed in Escherichia coli, purified to homogeneity, and studied using biochemical and crystallographic techniques. The dissociation constants of NAD+ and NADH have been determined over a broad pH range and indicate that SCHAD binds reduced cofactor preferentially. Examination of apparent catalytic constants reveals that SCHAD displays optimal enzymatic activity near neutral pH, with catalytic efficiency diminishing rapidly toward pH extremes. The crystal structure of SCHAD complexed with NAD+ has been solved using multiwavelength anomalous diffraction techniques and a selenomethionine-substituted analogue of the enzyme. The subunit structure is comprised of two domains. The first domain is similar to other alpha/beta dinucleotide folds but includes an unusual helix-turn-helix motif which extends from the central beta-sheet. The second, or C-terminal, domain is primarily alpha-helical and mediates subunit dimerization and, presumably, L-3-hydroxyacyl-CoA binding. Molecular modeling studies in which L-3-hydroxybutyryl-CoA was docked into the enzyme-NAD+ complex suggest that His 158 serves as a general base, abstracting a proton from the 3-OH group of the substrate. Furthermore, the ability of His 158 to perform such a function may be enhanced by an electrostatic interaction with Glu 170, consistent with previous biochemical observations. These studies provide further understanding of the molecular basis of several inherited metabolic disease states correlated with L-3-hydroxyacyl-CoA dehydrogenase deficiencies.


  • Organizational Affiliation

    Department of Biochemistry, Molecular Biology, and Biophysics, University of Minnesota, Minneapolis 55455, USA.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
L-3-HYDROXYACYL COA DEHYDROGENASE
A, B
293Homo sapiensMutation(s): 0 
EC: 1.1.1.35
UniProt & NIH Common Fund Data Resources
Find proteins for Q16836 (Homo sapiens)
Explore Q16836 
Go to UniProtKB:  Q16836
PHAROS:  Q16836
GTEx:  ENSG00000138796 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ16836
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 1 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
NAD
Query on NAD

Download Ideal Coordinates CCD File 
C [auth A],
D [auth B]
NICOTINAMIDE-ADENINE-DINUCLEOTIDE
C21 H27 N7 O14 P2
BAWFJGJZGIEFAR-NNYOXOHSSA-N
Modified Residues  1 Unique
IDChains TypeFormula2D DiagramParent
MSE
Query on MSE
A, B
L-PEPTIDE LINKINGC5 H11 N O2 SeMET
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.20 Å
  • R-Value Free: 0.251 
  • R-Value Work: 0.198 
  • Space Group: P 21 21 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 50.65α = 90
b = 86.5β = 90
c = 169.18γ = 90
Software Package:
Software NamePurpose
DENZOdata reduction
SCALEPACKdata scaling
SOLVEphasing
CNSrefinement

Structure Validation

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Ligand Structure Quality Assessment 


Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 1999-05-12
    Type: Initial release
  • Version 1.1: 2007-10-16
    Changes: Version format compliance
  • Version 1.2: 2011-07-13
    Changes: Derived calculations, Version format compliance
  • Version 1.3: 2023-12-27
    Changes: Data collection, Database references, Derived calculations