2le3

N-terminal regulatory segment of carnitine palmitoyltransferase 1A

spinqualitylabelsall models 2le3 Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 2le3 is a 1 chain structure with sequence from Homo sapiens. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: Solution NMR Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function CPT1A_HUMAN Publication Abstract from PubMed The enzyme carnitine palmitoyltransferase 1 (CPT1), which is anchored in the outer mitochondrial membrane (OMM), controls the rate-limiting step in fatty acid beta-oxidation in mammalian tissues. It is inhibited by malonyl-CoA, the first intermediate of fatty acid synthesis, and it responds to OMM curvature and lipid characteristics, which reflect long term nutrient/hormone availability. Here, we show that the N-terminal regulatory domain (N) of CPT1A can adopt two complex amphiphilic structural states, termed Nalpha and Nbeta, that interchange in a switch-like manner in response to offered binding surface curvature. Structure-based site-directed mutageneses of native CPT1A suggest Nalpha to be inhibitory and Nbeta to be noninhibitory, with the relative Nalpha/Nbeta ratio setting the prevalent malonyl-CoA sensitivity of the enzyme. Based on the amphiphilic nature of N and molecular modeling, we propose malonyl-CoA sensitivity to be coupled to the properties of the OMM by Nalpha-OMM associations that alter the Nalpha/Nbeta ratio. For enzymes residing at the membrane-water interface, this constitutes an integrative regulatory mechanism of exceptional sophistication. An Environment-dependent Structural Switch Underlies the Regulation of Carnitine Palmitoyltransferase 1A.,Rao JN, Warren GZ, Estolt-Povedano S, Zammit VA, Ulmer TS J Biol Chem. 2011 Dec 9;286(49):42545-54. Epub 2011 Oct 11. PMID:21990363 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Carnitine palmitoyltransferase

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