2M76

Structure of the Regulatory Domain of Human Brain Carnitine Palmitoyltransferase 1

2M76 の概要

• エントリーDOI: 10.2210/pdb2m76/pdb
• NMR情報: BMRB: 19174
• 分子名称: Carnitine O-palmitoyltransferase 1, brain isoform (1 entity in total)
• 機能のキーワード: acyl transfer, carnitine, malonyl-coenzyme a, signaling protein
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Mitochondrion outer membrane; Multi-pass membrane protein (By similarity): Q8TCG5
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 5711.41

構造登録者

Samanta, S.,Situ, A.J.,Ulmer, T.S. (登録日: 2013-04-18, 公開日: 2013-09-11, 最終更新日: 2024-05-15)

主引用文献

Samanta, S.,Situ, A.J.,Ulmer, T.S.
Structural characterization of the regulatory domain of brain carnitine palmitoyltransferase 1.
Biopolymers, 101:398-405, 2014

PubMed Abstract: Neurons contain a mammalian-specific isoform of the enzyme carnitine palmitoyltransferase 1 (CPT1C) that couples malonyl-CoA to ceramide levels thereby contributing to systemic energy homeostasis and feeding behavior. In contrast to CPT1A, which controls the rate-limiting step of long-chain fatty acid β-oxidation in all tissues, the biochemical context and regulatory mechanism of CPT1C are unknown. CPT1 enzymes are comprised of an N-terminal regulatory domain and a C-terminal catalytic domain (CD) that are separated by two transmembrane helices. In CPT1A, the regulatory domain, termed N, adopts an inhibitory and non-inhibitory state, Nα and Nβ, respectively, which differ in their association with the CD. To provide insight into the regulatory mechanism of CPT1C, we have determined the structure of its regulatory domain (residues Met1-Phe50) by NMR spectroscopy. In relation to CPT1A, the inhibitory Nα state was found to be structurally homologues whereas the non-inhibitory Nβ state was severely destabilized, suggesting a change in overall regulation. The destabilization of Nβ may contribute to the low catalytic activity of CPT1C relative to CPT1A and makes its association with the CD unlikely. In analogy to the stabilization of Nβ by the CPT1A CD, non-inhibitory interactions of N of CPT1C with another protein may exist.

PubMed: 24037959
DOI: 10.1002/bip.22396

実験手法

SOLUTION NMR