%0 Journal Article
%A Sonani, Ravi R.
%A Blat, Artur
%A Dubin, Grzegorz
%T Crystal structures of apo- and FAD-bound human peroxisomal acyl-CoA oxidase provide mechanistic basis explaining clinical observations
%J International journal of biological macromolecules
%V 205
%@ 0141-8130
%C New York, NY [u.a.]
%I Elsevier
%M PUBDB-2024-00618
%P 203 - 210
%D 2022
%X 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 (ΔGo) of −44.7 kcal mol−1. 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.
%F PUB:(DE-HGF)16
%9 Journal Article
%$ pmid:35149097
%U <Go to ISI:>//WOS:000784246800004
%R 10.1016/j.ijbiomac.2022.02.008
%U https://bib-pubdb1.desy.de/record/602498