2X24

bovine ACC2 CT domain in complex with inhibitor

Summary for 2X24

• Entry DOI: 10.2210/pdb2x24/pdb
• Descriptor: ACETYL-COA CARBOXYLASE, TERT-BUTYL [(TRANS-4-{[({2-[4-(AMINOMETHYL)PHENYL]QUINOLIN-4-YL}CARBONYL)AMINO]METHYL}CYCLOHEXYL)METHYL]CARBAMATE (3 entities in total)
• Functional Keywords: fatty acid biosynthesis, ligase, lipid synthesis
• Biological source: BOS TAURUS (CATTLE)
• Total number of polymer chains: 2
• Total formula weight: 179767.31

Authors

Oster, L.,Folmer, R.,Blaho, S.,Wiberg, F.,Hallberg, K. (deposition date: 2010-01-11, release date: 2011-01-26, Last modification date: 2024-05-08)

Primary citation

Bengtsson, C.,Blaho, S.,Saitton, D.B.,Brickmann, K.,Broddefalk, J.,Davidsson, O.,Drmota, T.,Folmer, R.,Hallberg, K.,Hallen, S.,Hovland, R.,Isin, E.,Johannesson, P.,Kull, B.,Larsson, L.,Lofgren, L.,Nilsson, K.E.,Noeske, T.,Oakes, N.,Plowright, A.T.,Schnecke, V.,Stahlberg, P.,Sorme, P.,Wan, H.,Wellner, E.,Oster, L.
Design of Small Molecule Inhibitors of Acetyl-Coa Carboxylase 1 and 2 Showing Reduction of Hepatic Malonyl-Coa Levels in Vivo in Obese Zucker Rats.
Bioorg.Med.Chem., 19:3039-, 2011

PubMed Abstract: Inhibition of acetyl-CoA carboxylases has the potential for modulating long chain fatty acid biosynthesis and mitochondrial fatty acid oxidation. Hybridization of weak inhibitors of ACC2 provided a novel, moderately potent but lipophilic series. Optimization led to compounds 33 and 37, which exhibit potent inhibition of human ACC2, 10-fold selectivity over inhibition of human ACC1, good physical and in vitro ADME properties and good bioavailability. X-ray crystallography has shown this series binding in the CT-domain of ACC2 and revealed two key hydrogen bonding interactions. Both 33 and 37 lower levels of hepatic malonyl-CoA in vivo in obese Zucker rats.

PubMed: 21515056
DOI: 10.1016/J.BMC.2011.04.014

Experimental method

X-RAY DIFFRACTION (2.4 Å)