1SG4

Crystal structure of human mitochondrial delta3-delta2-enoyl-CoA isomerase

Summary for 1SG4

• Entry DOI: 10.2210/pdb1sg4/pdb
• Descriptor: 3,2-trans-enoyl-CoA isomerase, mitochondrial, OCTANOYL-COENZYME A (3 entities in total)
• Functional Keywords: crotonase fold, isomerase
• Biological source: Homo sapiens (human)
• Cellular location: Mitochondrion matrix: P42126
• Total number of polymer chains: 3
• Total formula weight: 86747.63

Authors

Partanen, S.T.,Novikov, D.K.,Popov, A.N.,Mursula, A.M.,Hiltunen, J.K.,Wierenga, R.K. (deposition date: 2004-02-23, release date: 2005-01-18, Last modification date: 2024-02-14)

Primary citation

Partanen, S.T.,Novikov, D.K.,Popov, A.N.,Mursula, A.M.,Hiltunen, J.K.,Wierenga, R.K.
The 1.3 A crystal structure of human mitochondrial Delta3-Delta2-enoyl-CoA isomerase shows a novel mode of binding for the fatty acyl group.
J.Mol.Biol., 342:1197-1208, 2004

PubMed Abstract: The crystal structure of Delta3-Delta2-enoyl-CoA isomerase from human mitochondria (hmEci), complexed with the substrate analogue octanoyl-CoA, has been refined at 1.3 A resolution. This enzyme takes part in the beta-oxidation of unsaturated fatty acids by converting both cis-3 and trans-3-enoyl-CoA esters (with variable length of the acyl group) to trans-2-enoyl-CoA. hmEci belongs to the hydratase/isomerase (crotonase) superfamily. Most of the enzymes belonging to this superfamily are hexamers, but hmEci is shown to be a trimer. The mode of binding of the ligand, octanoyl-CoA, shows that the omega-end of the acyl group binds in a hydrophobic tunnel formed by residues of the loop preceding helix H4 as well as by side-chains of the kinked helix H9. From the structure of the complex it can be seen that Glu136 is the only catalytic residue. The importance of Glu136 for catalysis is confirmed by mutagenesis studies. A cavity analysis shows the presence of two large, adjacent empty hydrophobic cavities near the active site, which are shaped by side-chains of helices H1, H2, H3 and H4. The structure comparison of hmEci with structures of other superfamily members, in particular of rat mitochondrial hydratase (crotonase) and yeast peroxisomal enoyl-CoA isomerase, highlights the variable mode of binding of the fatty acid moiety in this superfamily.

PubMed: 15351645
DOI: 10.1016/j.jmb.2004.07.039

Experimental method

X-RAY DIFFRACTION (1.3 Å)