1WL5

Human cytosolic acetoacetyl-CoA thiolase


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.26 Å
  • R-Value Free: 0.194 
  • R-Value Work: 0.142 
  • R-Value Observed: 0.144 

wwPDB Validation   3D Report Full Report


This is version 1.2 of the entry. See complete history


Literature

High Resolution Crystal Structures of Human Cytosolic Thiolase (CT): A Comparison of the Active Sites of Human CT, Bacterial Thiolase, and Bacterial KAS I

Kursula, P.Sikkila, H.Fukao, T.Kondo, N.Wierenga, R.K.

(2005) J Mol Biol 347: 189-201

  • DOI: https://doi.org/10.1016/j.jmb.2005.01.018
  • Primary Citation of Related Structures:  
    1WL4, 1WL5

  • PubMed Abstract: 

    Thiolases belong to a superfamily of condensing enzymes that includes also beta-ketoacyl acyl carrier protein synthases (KAS enzymes), involved in fatty acid synthesis. Here, we describe the high resolution structure of human cytosolic acetoacetyl-CoA thiolase (CT), both unliganded (at 2.3 angstroms resolution) and in complex with CoA (at 1.6 angstroms resolution). CT catalyses the condensation of two molecules of acetyl-CoA to acetoacetyl-CoA, which is the first reaction of the metabolic pathway leading to the synthesis of cholesterol. CT is a homotetramer of exact 222 symmetry. There is an excess of positively charged residues at the interdimer surface leading towards the CoA-binding pocket, possibly important for the efficient capture of substrates. The geometry of the catalytic site, including the three catalytic residues Cys92, His 353, Cys383, and the two oxyanion holes, is highly conserved between the human and bacterial Zoogloea ramigera thiolase. In human CT, the first oxyanion hole is formed by Wat38 (stabilised by Asn321) and NE2(His353), and the second by N(Cys92) and N(Gly385). The active site of this superfamily is constructed on top of four active site loops, near Cys92, Asn321, His353, and Cys383, respectively. These loops were used for the superpositioning of CT on the bacterial thiolase and on the Escherichia coli KAS I. This comparison indicates that the two thiolase oxyanion holes also exist in KAS I at topologically equivalent positions. Interestingly, the hydrogen bonding interactions at the first oxyanion hole are different in thiolase and KAS I. In KAS I, the hydrogen bonding partners are two histidine NE2 atoms, instead of a water and a NE2 side-chain atom in thiolase. The second oxyanion hole is in both structures shaped by corresponding main chain peptide NH-groups. The possible importance of bound water molecules at the catalytic site of thiolase for the reaction mechanism is discussed.


  • Organizational Affiliation

    Department of Biochemistry and Biocenter Oulu, P.O. Box 3000, FIN-90014 University of Oulu, Oulu, Finland.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
acetyl-Coenzyme A acetyltransferase 2397Homo sapiensMutation(s): 1 
EC: 2.3.1.9
UniProt & NIH Common Fund Data Resources
Find proteins for Q9BWD1 (Homo sapiens)
Explore Q9BWD1 
Go to UniProtKB:  Q9BWD1
PHAROS:  Q9BWD1
GTEx:  ENSG00000120437 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ9BWD1
Sequence Annotations
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  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.26 Å
  • R-Value Free: 0.194 
  • R-Value Work: 0.142 
  • R-Value Observed: 0.144 
  • Space Group: I 2 2 2
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 57.85α = 90
b = 109.88β = 90
c = 155.64γ = 90
Software Package:
Software NamePurpose
REFMACrefinement
XDSdata reduction
XDSdata scaling
AMoREphasing

Structure Validation

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Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2005-03-01
    Type: Initial release
  • Version 1.1: 2008-04-30
    Changes: Version format compliance
  • Version 1.2: 2011-07-13
    Changes: Derived calculations, Version format compliance