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2iby
From Proteopedia
| 2iby, resolution 1.85Å () | |||||||||
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| Sites: | , , , , , , , , , , , , , and | ||||||||
| Ligands: | , , , , | ||||||||
| Non-Standard Residues: | |||||||||
| Gene: | ACAT1 (Homo sapiens) | ||||||||
| Activity: | Acetyl-CoA C-acetyltransferase, with EC number 2.3.1.9 | ||||||||
| Related: | 2ib7, 2ib8, 2ib9, 2ibu, 2ibw | ||||||||
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| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||||
Contents |
Crystallographic and kinetic studies of human mitochondrial acetoacetyl-CoA thiolase (T2): the importance of potassium and chloride for its structure and function
Thiolases are CoA-dependent enzymes which catalyze the formation of a carbon-carbon bond in a Claisen condensation step and its reverse reaction via a thiolytic degradation mechanism. Mitochondrial acetoacetyl-coenzyme A (CoA) thiolase (T2) is important in the pathways for the synthesis and degradation of ketone bodies as well as for the degradation of 2-methylacetoacetyl-CoA. Human T2 deficiency has been identified in more than 60 patients. A unique property of T2 is its activation by potassium ions. High-resolution human T2 crystal structures are reported for the apo form and the CoA complex, with and without a bound potassium ion. The potassium ion is bound near the CoA binding site and the catalytic site. Binding of the potassium ion at this low-affinity binding site causes the rigidification of a CoA binding loop and an active site loop. Unexpectedly, a high-affinity binding site for a chloride ion has also been identified. The chloride ion is copurified, and its binding site is at the dimer interface, near two catalytic loops. A unique property of T2 is its ability to use 2-methyl-branched acetoacetyl-CoA as a substrate, whereas the other structurally characterized thiolases cannot utilize the 2-methylated compounds. The kinetic measurements show that T2 can degrade acetoacetyl-CoA and 2-methylacetoacetyl-CoA with similar catalytic efficiencies. For both substrates, the turnover numbers increase approximately 3-fold when the potassium ion concentration is increased from 0 to 40 mM KCl. The structural analysis of the active site of T2 indicates that the Phe325-Pro326 dipeptide near the catalytic cavity is responsible for the exclusive 2-methyl-branched substrate specificity.
Crystallographic and kinetic studies of human mitochondrial acetoacetyl-CoA thiolase: the importance of potassium and chloride ions for its structure and function., Haapalainen AM, Merilainen G, Pirila PL, Kondo N, Fukao T, Wierenga RK, Biochemistry. 2007 Apr 10;46(14):4305-21. Epub 2007 Mar 20. PMID:17371050
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
Disease
Known disease associated with this structure: Alpha-methylacetoacetic aciduria OMIM:[607809]
About this Structure
2IBY is a 4 chains structure of sequences from Homo sapiens. Full crystallographic information is available from OCA. Relevant biological numbers for this protein at B10NUMB3R5
Reference
- Haapalainen AM, Merilainen G, Pirila PL, Kondo N, Fukao T, Wierenga RK. Crystallographic and kinetic studies of human mitochondrial acetoacetyl-CoA thiolase: the importance of potassium and chloride ions for its structure and function. Biochemistry. 2007 Apr 10;46(14):4305-21. Epub 2007 Mar 20. PMID:17371050 doi:10.1021/bi6026192
Page seeded by OCA on Mon May 25 08:07:29 2009
