2X58

The crystal structure of MFE1 liganded with CoA

Summary for 2X58

• Entry DOI: 10.2210/pdb2x58/pdb
• Related: 1ZCJ
• Descriptor: PEROXISOMAL BIFUNCTIONAL ENZYME, ADENOSINE-5'-DIPHOSPHATE, COENZYME A, ... (6 entities in total)
• Functional Keywords: beta oxidation pathway, oxidoreductase, lipid metabolism, lyase, isomerase, peroxisome, fatty acid metabolism
• Biological source: RATTUS NORVEGICUS (NORWAY RAT)
• Cellular location: Peroxisome: P07896
• Total number of polymer chains: 2
• Total formula weight: 161311.96

Authors

Kasaragod, P.,Venkatesan, R.,Kiema, T.R.,Hiltunen, J.K.,Wierenga, R.K. (deposition date: 2010-02-05, release date: 2010-05-12, Last modification date: 2023-12-20)

Primary citation

Kasaragod, P.,Venkatesan, R.,Kiema, T.R.,Hiltunen, J.K.,Wierenga, R.K.
The Crystal Structure of Liganded Rat Peroxisomal Multifunctional Enzyme Type 1: A Flexible Molecule with Two Interconnected Active Sites
J.Biol.Chem., 285:24089-, 2010

PubMed Abstract: The crystal structure of the full-length rat peroxisomal multifunctional enzyme, type 1 (rpMFE1), has been determined at 2.8 A resolution. This enzyme has three catalytic activities and two active sites. The N-terminal part has the crotonase fold, which builds the active site for the Delta(3),Delta(2)-enoyl-CoA isomerase and the Delta(2)-enoyl-CoA hydratase-1 catalytic activities, and the C-terminal part has the (3S)-hydroxyacyl-CoA dehydrogenase fold and makes the (3S)-hydroxyacyl-CoA dehydrogenase active site. rpMFE1 is a multidomain protein having five domains (A-E). The crystal structure of full-length rpMFE1 shows a flexible arrangement of the A-domain with respect to the B-E-domains. Because of a hinge region near the end of the A-domain, two different positions of the A-domain were observed for the two protein molecules (A and B) of the asymmetric unit. In the most closed conformation, the mode of binding of CoA is stabilized by domains A and B (helix-10), as seen in other crotonase fold members. Domain B, although functionally belonging to the N-terminal part, is found tightly associated with the C-terminal part, i.e. fixed to the E-domain. The two active sites of rpMFE1 are approximately 40 A apart, separated by a tunnel, characterized by an excess of positively charged side chains. Comparison of the structures of rpMFE1 with the monofunctional crotonase and (3S)-hydroxyacyl-CoA dehydrogenase superfamily enzymes, as well as with the bacterial alpha(2)beta(2)-fatty acid oxidation multienzyme complex, reveals that this tunnel could be important for substrate channeling, as observed earlier on the basis of the kinetics of rpMFE1 purified from rat liver.

PubMed: 20463028
DOI: 10.1074/JBC.M110.117606

Experimental method

X-RAY DIFFRACTION (2.8 Å)