4eph

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Current revision (15:06, 14 March 2024) (edit) (undo)
 
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== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[4eph]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4EPH OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4EPH FirstGlance]. <br>
<table><tr><td colspan='2'>[[4eph]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4EPH OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4EPH FirstGlance]. <br>
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</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=0RK:2-CHLORO-4-[({1-[(5-CHLORO-2-METHOXYPHENYL)SULFONYL]-4-METHYL-2,3-DIHYDRO-1H-INDOL-6-YL}CARBONYL)AMINO]BENZOIC+ACID'>0RK</scene>, <scene name='pdbligand=BOG:B-OCTYLGLUCOSIDE'>BOG</scene></td></tr>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.3&#8491;</td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=0RK:2-CHLORO-4-[({1-[(5-CHLORO-2-METHOXYPHENYL)SULFONYL]-4-METHYL-2,3-DIHYDRO-1H-INDOL-6-YL}CARBONYL)AMINO]BENZOIC+ACID'>0RK</scene>, <scene name='pdbligand=BOG:B-OCTYLGLUCOSIDE'>BOG</scene></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=4eph FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4eph OCA], [https://pdbe.org/4eph PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4eph RCSB], [https://www.ebi.ac.uk/pdbsum/4eph PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4eph ProSAT]</span></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=4eph FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4eph OCA], [https://pdbe.org/4eph PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4eph RCSB], [https://www.ebi.ac.uk/pdbsum/4eph PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4eph ProSAT]</span></td></tr>
</table>
</table>
== Function ==
== Function ==
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[[https://www.uniprot.org/uniprot/CPT2_RAT CPT2_RAT]]
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[https://www.uniprot.org/uniprot/CPT2_RAT CPT2_RAT]
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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Carnitine palmitoyl transferase 2 (CPT-2) is a key enzyme in the mitochondrial fatty acid metabolism. The active site is comprised of a Y-shaped tunnel with distinct binding sites for the substrate acylcarnitine and the cofactor CoA. We investigated the thermodynamics of binding of four inhibitors directed against either the CoA or the acylcarnitine binding sites using isothermal titration calorimetry (ITC). CPT-2 is a monotopic membrane protein and was solubilized by beta-octylglucoside (beta-OG) above its critical micellar concentration (CMC) to perform inhibitor titrations in solutions containing detergent micelles. The CMC of beta-OG in the presence of inhibitors was measured with ITC and small variations were observed. The inhibitors bound to rat CPT-2 (rCPT-2) with 1:1 stoichiometry and the dissociation constants were in the range of K D = 2-20 muM. New X-ray structures and docking models of rCPT-2 in complex with inhibitors enable an analysis of the thermodynamic data in the context of the interaction observed for the individual binding sites of the ligands. For all ligands the binding enthalpy was exothermic, and enthalpy as well as entropy contributed to the binding reaction, with the exception of ST1326 for which binding was solely enthalpy-driven. The substrate analog ST1326 binds to the acylcarnitine binding site and a heat capacity change close to zero suggests a balance of electrostatic and hydrophobic interactions. An excellent correlation of the thermodynamic (ITC) and structural (X-ray crystallography, models) data was observed suggesting that ITC measurements provide valuable information for optimizing inhibitor binding in drug discovery.
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Isothermal titration calorimetry with micelles: Thermodynamics of inhibitor binding to carnitine palmitoyltransferase 2 membrane protein.,Perspicace S, Rufer AC, Thoma R, Mueller F, Hennig M, Ceccarelli S, Schulz-Gasch T, Seelig J FEBS Open Bio. 2013 Apr 19;3:204-11. doi: 10.1016/j.fob.2013.04.003. Print 2013. PMID:23772395<ref>PMID:23772395</ref>
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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</div>
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<div class="pdbe-citations 4eph" style="background-color:#fffaf0;"></div>
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==See Also==
==See Also==
*[[Carnitine palmitoyltransferase|Carnitine palmitoyltransferase]]
*[[Carnitine palmitoyltransferase|Carnitine palmitoyltransferase]]
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== References ==
 
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<references/>
 
__TOC__
__TOC__
</StructureSection>
</StructureSection>

Current revision

CRYSTAL STRUCTURE OF RAT CARNITINE PALMITOYLTRANSFERASE 2 IN COMPLEX with CoA-site inhibitor

PDB ID 4eph

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