View source for 2ib8

[[Image:2ib8.jpg|left|200px]]<br /><applet load="2ib8" size="350" color="white" frame="true" align="right" spinBox="true" 
caption="2ib8, resolution 1.85&Aring;" />
'''Crystallographic and kinetic studies of human mitochondrial acetoacetyl-CoA thiolase (T2): the importance of potassium and chloride for its structure and function'''<br />

==Overview==
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.

==Disease==
Known diseases associated with this structure: Alpha-methylacetoacetic aciduria OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=607809 607809]], Hypermethioninemia, persistent, autosomal dominant, due to methionine adenosyltransferase I/III deficiency OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=250850 250850]], Methionine adenosyltransferase deficiency, autosomal recessive OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=250850 250850]]

==About this Structure==
2IB8 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=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=2IB8 OCA]. 

==Reference==
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:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=17371050 17371050]
[[Category: Acetyl-CoA C-acetyltransferase]]
[[Category: Homo sapiens]]
[[Category: Single protein]]
[[Category: Haapalainen, A.M.]]
[[Category: Wierenga, R.K.]]
[[Category: CL]]
[[Category: GOL]]
[[Category: K]]
[[Category: MES]]
[[Category: alpha-beta-alpha-beta-alpha layered structure]]
[[Category: beta-alpha-beta-alpha-beta-alpha-beta-beta topology]]
[[Category: chloride]]
[[Category: potassium ion]]
[[Category: thiolase fold]]

''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri Feb 15 17:35:31 2008''