2bu2: Difference between revisions
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|PDB= 2bu2 |SIZE=350|CAPTION= <scene name='initialview01'>2bu2</scene>, resolution 2.4Å | |PDB= 2bu2 |SIZE=350|CAPTION= <scene name='initialview01'>2bu2</scene>, resolution 2.4Å | ||
|SITE= <scene name='pdbsite=AC1:Mg+Binding+Site+For+Chain+A'>AC1</scene> | |SITE= <scene name='pdbsite=AC1:Mg+Binding+Site+For+Chain+A'>AC1</scene> | ||
|LIGAND= <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=ATP:ADENOSINE-5 | |LIGAND= <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=ATP:ADENOSINE-5'-TRIPHOSPHATE'>ATP</scene> and <scene name='pdbligand=TF1:4-({(2R,5S)-2,5-DIMETHYL-4-[(2R)-3,3,3-TRIFLUORO-2-HYDROXY-2-METHYLPROPANOYL]PIPERAZIN-1-YL}CARBONYL)BENZONITRILE'>TF1</scene> | ||
|ACTIVITY= [http://en.wikipedia.org/wiki/Transferred_entry:_2.7.11.2 Transferred entry: 2.7.11.2], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.1.99 2.7.1.99] | |ACTIVITY= [http://en.wikipedia.org/wiki/Transferred_entry:_2.7.11.2 Transferred entry: 2.7.11.2], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.1.99 2.7.1.99] | ||
|GENE= | |GENE= | ||
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[[Category: transferase]] | [[Category: transferase]] | ||
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Mar 23 14:47:56 2008'' | ||
Revision as of 15:47, 23 March 2008
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| , resolution 2.4Å | |||||||
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| Ligands: | , and | ||||||
| Activity: | Transferred entry: 2.7.11.2, with EC number 2.7.1.99 | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
CRYSTAL STRUCTURES OF HUMAN PYRUVATE DEHYDROGENASE KINASE 2 CONTAINING PHYSIOLOGICAL AND SYNTHETIC LIGANDS
OverviewOverview
Pyruvate dehydrogenase kinase (PDHK) regulates the activity of the pyruvate dehydrogenase multienzyme complex. PDHK inhibition provides a route for therapeutic intervention in diabetes and cardiovascular disorders. We report crystal structures of human PDHK isozyme 2 complexed with physiological and synthetic ligands. Several of the PDHK2 structures disclosed have C-terminal cross arms that span a large trough region between the N-terminal regulatory (R) domains of the PDHK2 dimers. The structures containing bound ATP and ADP demonstrate variation in the conformation of the active site lid, residues 316-321, which enclose the nucleotide beta and gamma phosphates at the active site in the C-terminal catalytic domain. We have identified three novel ligand binding sites located in the R domain of PDHK2. Dichloroacetate (DCA) binds at the pyruvate binding site in the center of the R domain, which together with ADP, induces significant changes at the active site. Nov3r and AZ12 inhibitors bind at the lipoamide binding site that is located at one end of the R domain. Pfz3 (an allosteric inhibitor) binds in an extended site at the other end of the R domain. We conclude that the N-terminal domain of PDHK has a key regulatory function and propose that the different inhibitor classes act by discrete mechanisms. The structures we describe provide insights that can be used for structure-based design of PDHK inhibitors.
About this StructureAbout this Structure
2BU2 is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
ReferenceReference
Regulatory roles of the N-terminal domain based on crystal structures of human pyruvate dehydrogenase kinase 2 containing physiological and synthetic ligands., Knoechel TR, Tucker AD, Robinson CM, Phillips C, Taylor W, Bungay PJ, Kasten SA, Roche TE, Brown DG, Biochemistry. 2006 Jan 17;45(2):402-15. PMID:16401071
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