7Q84

Crystal structure of human peroxisomal acyl-Co-A oxidase 1a, apo-form

Summary for 7Q84

• Entry DOI: 10.2210/pdb7q84/pdb
• Descriptor: Isoform 2 of Peroxisomal acyl-coenzyme A oxidase 1, TRIETHYLENE GLYCOL, 1,2-ETHANEDIOL, ... (6 entities in total)
• Functional Keywords: acyl-co-a oxidase, peroxisomal enzyme, oxidoreductase
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 2
• Total formula weight: 152810.71

Authors

Sonani, R.R.,Blat, A.,Dubin, G. (deposition date: 2021-11-10, release date: 2022-03-02, Last modification date: 2024-11-06)

Primary citation

Sonani, R.R.,Blat, A.,Dubin, G.
Crystal structures of apo- and FAD-bound human peroxisomal acyl-CoA oxidase provide mechanistic basis explaining clinical observations.
Int.J.Biol.Macromol., 205:203-210, 2022

PubMed Abstract: Peroxisomal acyl-CoA oxidase 1a (ACOX1a) catalyzes the first and rate-limiting step of fatty acid oxidation, the conversion of acyl-CoAs to 2-trans-enoyl-CoAs. The dysfunction of human ACOX1a (hACOX1a) leads to deterioration of the nervous system manifesting in myeloneuropathy, hypotonia and convulsions. Crystal structures of hACOX1a in apo- and cofactor (FAD)-bound forms were solved at 2.00 and 2.09 Å resolution, respectively. hACOX1a exists as a homo-dimer with solvation free energy gain (ΔG) of -44.7 kcal mol. Two FAD molecules bind at the interface of protein monomers completing the active sites. The substrate binding cleft of hACOX1a is wider compared to human mitochondrial very-long chain specific acyl-CoA dehydrogenase. Mutations (p.G178C, p.M278V and p.N237S) reported to cause dysfunctionality of hACOX1a are analyzed on its 3D-structure to understand structure-function related perturbations and explain the associated phenotypes.

PubMed: 35149097
DOI: 10.1016/j.ijbiomac.2022.02.008

Experimental method

X-RAY DIFFRACTION (2 Å)