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Crystal structure of the liganded SCP-2-like domain of human peroxisomal multifunctional enzyme type 2 at 1.75 A resolution.
- Source :
-
Journal of molecular biology [J Mol Biol] 2001 Nov 09; Vol. 313 (5), pp. 1127-38. - Publication Year :
- 2001
-
Abstract
- beta-Oxidation of amino acyl coenzyme A (acyl-CoA) species in mammalian peroxisomes can occur via either multifunctional enzyme type 1 (MFE-1) or type 2 (MFE-2), both of which catalyze the hydration of trans-2-enoyl-CoA and the dehydrogenation of 3-hydroxyacyl-CoA, but with opposite chiral specificity. MFE-2 has a modular organization of three domains. The function of the C-terminal domain of the mammalian MFE-2, which shows similarity with sterol carrier protein type 2 (SCP-2), is unclear. Here, the structure of the SCP-2-like domain comprising amino acid residues 618-736 of human MFE-2 (d Delta h Delta SCP-2L) was solved at 1.75 A resolution in complex with Triton X-100, an analog of a lipid molecule. This is the first reported structure of an MFE-2 domain. The d Delta h Delta SCP-2L has an alpha/beta-fold consisting of five beta-strands and five alpha-helices; the overall architecture resembles the rabbit and human SCP-2 structures. However, the structure of d Delta h Delta SCP-2L shows a hydrophobic tunnel that traverses the protein, which is occupied by an ordered Triton X-100 molecule. The tunnel is large enough to accommodate molecules such as straight-chain and branched-chain fatty acyl-CoAs and bile acid intermediates. Large empty apolar cavities are observed near the exit of the tunnel and between the helices C and D. In addition, the C-terminal peroxisomal targeting signal is ordered in the structure and solvent-exposed, which is not the case with unliganded rabbit SCP-2, supporting the hypothesis of a ligand-assisted targeting mechanism.<br /> (Copyright 2001 Academic Press.)
- Subjects :
- Amino Acid Sequence
Binding Sites
Crystallography, X-Ray
Humans
Ligands
Models, Molecular
Molecular Sequence Data
Octoxynol chemistry
Protein Binding
Protein Structure, Secondary
Protein Structure, Tertiary
Sequence Alignment
Static Electricity
Structure-Activity Relationship
Surface Plasmon Resonance
3-Hydroxyacyl CoA Dehydrogenases chemistry
3-Hydroxyacyl CoA Dehydrogenases metabolism
Carrier Proteins chemistry
Enoyl-CoA Hydratase chemistry
Enoyl-CoA Hydratase metabolism
Multienzyme Complexes chemistry
Multienzyme Complexes metabolism
Octoxynol metabolism
Plant Proteins
Subjects
Details
- Language :
- English
- ISSN :
- 0022-2836
- Volume :
- 313
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- Journal of molecular biology
- Publication Type :
- Academic Journal
- Accession number :
- 11700068
- Full Text :
- https://doi.org/10.1006/jmbi.2001.5084