2ib8: Difference between revisions
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|PDB= 2ib8 |SIZE=350|CAPTION= <scene name='initialview01'>2ib8</scene>, resolution 1.85Å | |PDB= 2ib8 |SIZE=350|CAPTION= <scene name='initialview01'>2ib8</scene>, resolution 1.85Å | ||
|SITE= | |SITE= | ||
|LIGAND= <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=K:POTASSIUM+ION'>K</scene>, <scene name='pdbligand=MES:2-(N-MORPHOLINO)-ETHANESULFONIC+ACID'>MES</scene> | |LIGAND= <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=K:POTASSIUM+ION'>K</scene>, <scene name='pdbligand=MES:2-(N-MORPHOLINO)-ETHANESULFONIC+ACID'>MES</scene> | ||
|ACTIVITY= <span class='plainlinks'>[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] </span> | |||
|GENE= ACAT1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]) | |GENE= ACAT1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]) | ||
|DOMAIN= | |||
|RELATEDENTRY=[[2ib7|2IB7]], [[2ib9|2IB9]], [[2ibu|2IBU]], [[2ibw|2IBW]], [[2iby|2IBY]] | |||
|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2ib8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2ib8 OCA], [http://www.ebi.ac.uk/pdbsum/2ib8 PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=2ib8 RCSB]</span> | |||
}} | }} | ||
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==Disease== | ==Disease== | ||
Known | Known disease associated with this structure: Alpha-methylacetoacetic aciduria OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=607809 607809]] | ||
==About this Structure== | ==About this Structure== | ||
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[[Category: Haapalainen, A M.]] | [[Category: Haapalainen, A M.]] | ||
[[Category: Wierenga, R K.]] | [[Category: Wierenga, R K.]] | ||
[[Category: alpha-beta-alpha-beta-alpha layered structure]] | [[Category: alpha-beta-alpha-beta-alpha layered structure]] | ||
[[Category: beta-alpha-beta-alpha-beta-alpha-beta-beta topology]] | [[Category: beta-alpha-beta-alpha-beta-alpha-beta-beta topology]] | ||
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[[Category: thiolase fold]] | [[Category: thiolase fold]] | ||
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 03:41:55 2008'' | ||
Revision as of 03:41, 31 March 2008
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| , resolution 1.85Å | |||||||
|---|---|---|---|---|---|---|---|
| Ligands: | , , , | ||||||
| Gene: | ACAT1 (Homo sapiens) | ||||||
| Activity: | Acetyl-CoA C-acetyltransferase, with EC number 2.3.1.9 | ||||||
| Related: | 2IB7, 2IB9, 2IBU, 2IBW, 2IBY
| ||||||
| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
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 disease associated with this structure: Alpha-methylacetoacetic aciduria OMIM:[607809]
About this StructureAbout this Structure
2IB8 is a Single protein structure of sequence from Homo sapiens. 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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