2le3: Difference between revisions
New page: '''Unreleased structure''' The entry 2le3 is ON HOLD Authors: Ulmer, T.S., Rao, J.N. Description: N-terminal regulatory segment of carnitine palmitoyltransferase 1A |
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The | ==N-terminal regulatory segment of carnitine palmitoyltransferase 1A== | ||
<StructureSection load='2le3' size='340' side='right'caption='[[2le3]]' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[2le3]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2LE3 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2LE3 FirstGlance]. <br> | |||
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR</td></tr> | |||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2le3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2le3 OCA], [https://pdbe.org/2le3 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2le3 RCSB], [https://www.ebi.ac.uk/pdbsum/2le3 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2le3 ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/CPT1A_HUMAN CPT1A_HUMAN] | |||
<div style="background-color:#fffaf0;"> | |||
== 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<ref>PMID:21990363</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 2le3" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[Carnitine palmitoyltransferase|Carnitine palmitoyltransferase]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Homo sapiens]] | |||
[[Category: Large Structures]] | |||
[[Category: Rao JN]] | |||
[[Category: Ulmer TS]] | |||
Latest revision as of 08:42, 15 May 2024
N-terminal regulatory segment of carnitine palmitoyltransferase 1AN-terminal regulatory segment of carnitine palmitoyltransferase 1A
Structural highlights
FunctionPublication Abstract from PubMedThe 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[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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