8W0U

Human LCAD complexed with Acetoacetyl Coenzyme A

8W0U の概要

• エントリーDOI: 10.2210/pdb8w0u/pdb
• 関連するPDBエントリー: 8W0T
• 分子名称: Long-chain specific acyl-CoA dehydrogenase, mitochondrial, FLAVIN-ADENINE DINUCLEOTIDE, ACETOACETYL-COENZYME A, ... (4 entities in total)
• 機能のキーワード: fatty acid beta-oxidation, lcad, flavoprotein, cholesterol metabolism
• 由来する生物種: Homo sapiens (human)
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 182824.40

構造登録者

Xia, C.,Kim, J.J.P. (登録日: 2024-02-14, 公開日: 2024-06-19)

主引用文献

Narayanan, B.,Xia, C.,McAndrew, R.,Shen, A.L.,Kim, J.P.
Structural basis for expanded substrate specificities of human long chain acyl-CoA dehydrogenase and related acyl-CoA dehydrogenases.
Sci Rep, 14:12976-12976, 2024

PubMed Abstract: Crystal structures of human long-chain acyl-CoA dehydrogenase (LCAD) and the catalytically inactive Glu291Gln mutant, have been determined. These structures suggest that LCAD harbors functions beyond its historically defined role in mitochondrial β-oxidation of long and medium-chain fatty acids. LCAD is a homotetramer containing one FAD per 43 kDa subunit with Glu291 as the catalytic base. The substrate binding cavity of LCAD reveals key differences which makes it specific for longer and branched chain substrates. The presence of Pro132 near the start of the E helix leads to helix unwinding that, together with adjacent smaller residues, permits binding of bulky substrates such as 3α, 7α, l2α-trihydroxy-5β-cholestan-26-oyl-CoA. This structural element is also utilized by ACAD11, a eucaryotic ACAD of unknown function, as well as bacterial ACADs known to metabolize sterol substrates. Sequence comparison suggests that ACAD10, another ACAD of unknown function, may also share this substrate specificity. These results suggest that LCAD, ACAD10, ACAD11 constitute a distinct class of eucaryotic acyl CoA dehydrogenases.

PubMed: 38839792
DOI: 10.1038/s41598-024-63027-6

実験手法

X-RAY DIFFRACTION (2.8 Å)