4C2J: Crystal Structure Of Human Mitochondrial 3-ketoacyl-coa Thiolase In Complex With Coa

Crystal structures of human mitochondrial 3-ketoacyl-CoA thiolase (hT1) in the apo form and in complex with CoA have been determined at 2.0 A resolution. The structures confirm the tetrameric quaternary structure of this degradative thiolase. The active site is surprisingly similar to the active site of the Zoogloea ramigera biosynthetic tetrameric thiolase (PDB entries 1dm3 and 1m1o) and different from the active site of the peroxisomal dimeric degradative thiolase (PDB entries 1afw and 2iik). A cavity analysis suggests a mode of binding for the fatty-acyl tail in a tunnel lined by the Nbeta2-Nalpha2 loop of the adjacent subunit and the Lalpha1 helix of the loop domain. Soaking of the apo hT1 crystals with octanoyl-CoA resulted in a crystal structure in complex with CoA owing to the intrinsic acyl-CoA thioesterase activity of hT1. Solution studies confirm that hT1 has low acyl-CoA thioesterase activity for fatty acyl-CoA substrates. The fastest rate is observed for the hydrolysis of butyryl-CoA. It is also shown that T1 has significant biosynthetic thiolase activity, which is predicted to be of physiological importance.
PDB ID: 4C2JDownload
MMDB ID: 122822
PDB Deposition Date: 2013/8/19
Updated in MMDB: 2014/12
Experimental Method:
x-ray diffraction
Resolution: 2  Å
Source Organism:
Similar Structures:
Biological Unit for 4C2J: dimeric; determined by author and by software (PISA)
Molecular Components in 4C2J
Label Count Molecule
Proteins (2 molecules)
3-ketoacyl-coa Thiolase, Mitochondrial(Gene symbol: ACAA2)
Molecule annotation
Chemicals (10 molecules)
* Click molecule labels to explore molecular sequence information.

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