TY  - JOUR
AU  - Sonani, Ravi R.
AU  - Blat, Artur
AU  - Dubin, Grzegorz
TI  - Crystal structures of apo- and FAD-bound human peroxisomal acyl-CoA oxidase provide mechanistic basis explaining clinical observations
JO  - International journal of biological macromolecules
VL  - 205
SN  - 0141-8130
CY  - New York, NY [u.a.]
PB  - Elsevier
M1  - PUBDB-2024-00618
SP  - 203 - 210
PY  - 2022
AB  - 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.
LB  - PUB:(DE-HGF)16
C6  - pmid:35149097
UR  - <Go to ISI:>//WOS:000784246800004
DO  - DOI:10.1016/j.ijbiomac.2022.02.008
UR  - https://bib-pubdb1.desy.de/record/602498
ER  -