PDBsum entry 4eyw

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Transferase/transferase inhibitor PDB id
Protein chains
627 a.a.
L0R ×2
P6G ×2
Waters ×1189
PDB id:
Name: Transferase/transferase inhibitor
Title: Crystal structure of rat carnitine palmitoyltransferase 2 in with 1-[(r)-2-(3,4-dihydro-1h-isoquinoline-2-carbonyl)-pipe yl]-2-phenoxy-ethanone
Structure: Carnitine o-palmitoyltransferase 2, mitochondrial chain: a, b. Fragment: unp residues 27-658. Synonym: carnitine palmitoyltransferase ii, cpt ii. Engineered: yes
Source: Rattus norvegicus. Brown rat,rat,rats. Organism_taxid: 10116. Gene: cpt2, cpt-2. Expressed in: escherichia coli. Expression_system_taxid: 469008.
1.89Å     R-factor:   0.174     R-free:   0.197
Authors: M.G.Rudolph,J.Benz,D.Burger,R.Thoma,A.Rufer,C.Joseph
Key ref: S.Perspicace et al. (2013). Isothermal titration calorimetry with micelles: Thermodynamics of inhibitor binding to carnitine palmitoyltransferase 2 membrane protein. FEBS Open Bio, 3, 204-211. PubMed id: 23772395 DOI: 10.1016/j.fob.2013.04.003
02-May-12     Release date:   24-Apr-13    
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Protein chains
Pfam   ArchSchema ?
P18886  (CPT2_RAT) -  Carnitine O-palmitoyltransferase 2, mitochondrial
658 a.a.
627 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     membrane   3 terms 
  Biological process     transport   5 terms 
  Biochemical function     transferase activity     3 terms  


DOI no: 10.1016/j.fob.2013.04.003 FEBS Open Bio 3:204-211 (2013)
PubMed id: 23772395  
Isothermal titration calorimetry with micelles: Thermodynamics of inhibitor binding to carnitine palmitoyltransferase 2 membrane protein.
S.Perspicace, A.C.Rufer, R.Thoma, F.Mueller, M.Hennig, S.Ceccarelli, T.Schulz-Gasch, J.Seelig.
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 β-octylglucoside (β-OG) above its critical micellar concentration (CMC) to perform inhibitor titrations in solutions containing detergent micelles. The CMC of β-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 μM. 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.