2ibw: Difference between revisions
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'''Crystallographic and kinetic studies of human mitochondrial acetoacetyl-CoA thiolase (T2): the importance of potassium and chloride for its structure and function'''<br /> | '''Crystallographic and kinetic studies of human mitochondrial acetoacetyl-CoA thiolase (T2): the importance of potassium and chloride for its structure and function'''<br /> | ||
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==About this Structure== | ==About this Structure== | ||
2IBW is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with CL, K, COA, MES and GOL as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Acetyl-CoA_C-acetyltransferase Acetyl-CoA C-acetyltransferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.3.1.9 2.3.1.9] Full crystallographic information is available from [http:// | 2IBW is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=CL:'>CL</scene>, <scene name='pdbligand=K:'>K</scene>, <scene name='pdbligand=COA:'>COA</scene>, <scene name='pdbligand=MES:'>MES</scene> and <scene name='pdbligand=GOL:'>GOL</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Acetyl-CoA_C-acetyltransferase Acetyl-CoA C-acetyltransferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.3.1.9 2.3.1.9] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2IBW OCA]. | ||
==Reference== | ==Reference== | ||
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[[Category: thiolase fold]] | [[Category: thiolase fold]] | ||
''Page seeded by [http:// | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri Feb 15 17:35:44 2008'' | ||
Revision as of 18:35, 15 February 2008
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Crystallographic and kinetic studies of human mitochondrial acetoacetyl-CoA thiolase (T2): the importance of potassium and chloride for its structure and function
OverviewOverview
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.
DiseaseDisease
Known diseases associated with this structure: Alpha-methylacetoacetic aciduria OMIM:[607809], Hypermethioninemia, persistent, autosomal dominant, due to methionine adenosyltransferase I/III deficiency OMIM:[250850], Methionine adenosyltransferase deficiency, autosomal recessive OMIM:[250850]
About this StructureAbout this Structure
2IBW is a Single protein structure of sequence from Homo sapiens with , , , and as ligands. Active as Acetyl-CoA C-acetyltransferase, with EC number 2.3.1.9 Full crystallographic information is available from OCA.
ReferenceReference
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
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