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@ARTICLE{Sonani:602498,
author = {Sonani, Ravi R. and Blat, Artur and Dubin, Grzegorz},
title = {{C}rystal structures of apo- and {FAD}-bound human
peroxisomal acyl-{C}o{A} oxidase provide mechanistic basis
explaining clinical observations},
journal = {International journal of biological macromolecules},
volume = {205},
issn = {0141-8130},
address = {New York, NY [u.a.]},
publisher = {Elsevier},
reportid = {PUBDB-2024-00618},
pages = {203 - 210},
year = {2022},
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 (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.},
cin = {EMBL-User},
ddc = {570},
cid = {I:(DE-H253)EMBL-User-20120814},
pnm = {6G3 - PETRA III (DESY) (POF4-6G3)},
pid = {G:(DE-HGF)POF4-6G3},
experiment = {EXP:(DE-H253)P-P13-20150101},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:35149097},
UT = {WOS:000784246800004},
doi = {10.1016/j.ijbiomac.2022.02.008},
url = {https://bib-pubdb1.desy.de/record/602498},
}