1IKT

LIGANDED STEROL CARRIER PROTEIN TYPE 2 (SCP-2) LIKE DOMAIN OF HUMAN MULTIFUNCTIONAL ENZYME TYPE 2 (MFE-2)

Summary for 1IKT

• Entry DOI: 10.2210/pdb1ikt/pdb
• Descriptor: ESTRADIOL 17 BETA-DEHYDROGENASE 4, SULFATE ION, OXTOXYNOL-10, ... (4 entities in total)
• Functional Keywords: alfa-beta fold, protein-triton x-100 complex, hydrophobic tunnel, exposed peroxisomal targeting signal type 1 (pts1), oxidoreductase
• Biological source: Homo sapiens (human)
• Cellular location: Peroxisome: P51659
• Total number of polymer chains: 1
• Total formula weight: 14103.44

Authors

Haapalainen, A.M.,van Aalten, D.M.F.,Glumoff, T. (deposition date: 2001-05-07, release date: 2001-11-14, Last modification date: 2023-08-16)

Primary citation

Haapalainen, A.M.,van Aalten, D.M.,Merilainen, G.,Jalonen, J.E.,Pirila, P.,Wierenga, R.K.,Hiltunen, J.K.,Glumoff, T.
Crystal structure of the liganded SCP-2-like domain of human peroxisomal multifunctional enzyme type 2 at 1.75 A resolution.
J.Mol.Biol., 313:1127-1138, 2001

PubMed 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.

PubMed: 11700068
DOI: 10.1006/jmbi.2001.5084

Experimental method

X-RAY DIFFRACTION (1.75 Å)