Structural highlights
FunctionPublication Abstract from PubMedNeurons 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 beta-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 that are separated by two transmembrane helices. In CPT1A, the regulatory domain, termed N, adopts an inhibitory and non-inhibitory state, Nalpha and Nbeta, respectively, which differ in their association with the catalytic domain. 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 Nalpha state was found to be structurally homologues whereas the non-inhibitory Nbeta state was severely destabilized, suggesting a change in overall regulation. The destabilization of Nbeta may contribute to the low catalytic activity of CPT1C relative to CPT1A and makes its association with the catalytic domain unlikely. In analogy to the stabilization of Nbeta by the CPT1A catalytic domain, non-inhibitory interactions of N of CPT1C with another protein may exist. (c) 2013 Wiley Periodicals, Inc. Biopolymers, 2013. Structural characterization of the regulatory domain of brain carnitine palmitoyltransferase 1.,Samanta S, Situ AJ, Ulmer TS Biopolymers. 2013 Aug 27. doi: 10.1002/bip.22396. PMID:24037959[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
| ||||||||||||||||||
This page was last modified 06:01, 15 May 2024.