2M76
Structure of the Regulatory Domain of Human Brain Carnitine Palmitoyltransferase 1
Summary for 2M76
| Entry DOI | 10.2210/pdb2m76/pdb |
| NMR Information | BMRB: 19174 |
| Descriptor | Carnitine O-palmitoyltransferase 1, brain isoform (1 entity in total) |
| Functional Keywords | acyl transfer, carnitine, malonyl-coenzyme a, signaling protein |
| Biological source | Homo sapiens (human) |
| Cellular location | Mitochondrion outer membrane; Multi-pass membrane protein (By similarity): Q8TCG5 |
| Total number of polymer chains | 1 |
| Total formula weight | 5711.41 |
| Authors | Samanta, S.,Situ, A.J.,Ulmer, T.S. (deposition date: 2013-04-18, release date: 2013-09-11, Last modification date: 2024-05-15) |
| Primary citation | Samanta, S.,Situ, A.J.,Ulmer, T.S. Structural characterization of the regulatory domain of brain carnitine palmitoyltransferase 1. Biopolymers, 101:398-405, 2014 Cited by 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: 24037959DOI: 10.1002/bip.22396 PDB entries with the same primary citation |
| Experimental method | SOLUTION NMR |
Structure validation
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