1y8o: Difference between revisions

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[[Image:1y8o.gif|left|200px]]
{{Seed}}
[[Image:1y8o.png|left|200px]]


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{{STRUCTURE_1y8o|  PDB=1y8o  |  SCENE=  }}  
{{STRUCTURE_1y8o|  PDB=1y8o  |  SCENE=  }}  


'''Crystal structure of the PDK3-L2 complex'''
===Crystal structure of the PDK3-L2 complex===




==Overview==
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The human pyruvate dehydrogenase complex (PDC) is regulated by reversible phosphorylation by four isoforms of pyruvate dehydrogenase kinase (PDK). PDKs phosphorylate serine residues in the dehydrogenase (E1p) component of PDC, but their amino-acid sequences are unrelated to eukaryotic Ser/Thr/Tyr protein kinases. PDK3 binds to the inner lipoyl domains (L2) from the 60-meric transacetylase (E2p) core of PDC, with concomitant stimulated kinase activity. Here, we present crystal structures of the PDK3-L2 complex with and without bound ADP or ATP. These structures disclose that the C-terminal tail from one subunit of PDK3 dimer constitutes an integral part of the lipoyl-binding pocket in the N-terminal domain of the opposing subunit. The two swapped C-terminal tails promote conformational changes in active-site clefts of both PDK3 subunits, resulting in largely disordered ATP lids in the ADP-bound form. Our structural and biochemical data suggest that L2 binding stimulates PDK3 activity by disrupting the ATP lid, which otherwise traps ADP, to remove product inhibition exerted by this nucleotide. We hypothesize that this allosteric mechanism accounts, in part, for E2p-augmented PDK3 activity.
The line below this paragraph, {{ABSTRACT_PUBMED_15861126}}, adds the Publication Abstract to the page
(as it appears on PubMed at http://www.pubmed.gov), where 15861126 is the PubMed ID number.
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{{ABSTRACT_PUBMED_15861126}}


==About this Structure==
==About this Structure==
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[[Category: Protein-protein complex]]
[[Category: Protein-protein complex]]
[[Category: Pyruvate dehydrogenase kinase 3]]
[[Category: Pyruvate dehydrogenase kinase 3]]
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May  3 16:00:47 2008''
 
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Jul 28 11:06:13 2008''

Revision as of 08:06, 28 July 2008

File:1y8o.png

Template:STRUCTURE 1y8o

Crystal structure of the PDK3-L2 complex

Template:ABSTRACT PUBMED 15861126

About this Structure

1Y8O is a Protein complex structure of sequences from Homo sapiens. Full crystallographic information is available from OCA.

Reference

Crystal structure of pyruvate dehydrogenase kinase 3 bound to lipoyl domain 2 of human pyruvate dehydrogenase complex., Kato M, Chuang JL, Tso SC, Wynn RM, Chuang DT, EMBO J. 2005 May 18;24(10):1763-74. Epub 2005 Apr 28. PMID:15861126

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