1y8n
From Proteopedia
(New page: 200px<br /> <applet load="1y8n" size="450" color="white" frame="true" align="right" spinBox="true" caption="1y8n, resolution 2.60Å" /> '''Crystal structure o...) |
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| - | [[Image:1y8n.gif|left|200px]]<br /> | + | [[Image:1y8n.gif|left|200px]]<br /><applet load="1y8n" size="350" color="white" frame="true" align="right" spinBox="true" |
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caption="1y8n, resolution 2.60Å" /> | caption="1y8n, resolution 2.60Å" /> | ||
'''Crystal structure of the PDK3-L2 complex'''<br /> | '''Crystal structure of the PDK3-L2 complex'''<br /> | ||
==Overview== | ==Overview== | ||
| - | The human pyruvate dehydrogenase complex (PDC) is regulated by reversible | + | 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. |
==About this Structure== | ==About this Structure== | ||
| - | 1Y8N is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with K and LPA as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/[Pyruvate_dehydrogenase_(acetyl-transferring)]_kinase [Pyruvate dehydrogenase (acetyl-transferring)] kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.2 2.7.11.2] Full crystallographic information is available from [http:// | + | 1Y8N is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=K:'>K</scene> and <scene name='pdbligand=LPA:'>LPA</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/[Pyruvate_dehydrogenase_(acetyl-transferring)]_kinase [Pyruvate dehydrogenase (acetyl-transferring)] kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.2 2.7.11.2] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1Y8N OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Protein complex]] | [[Category: Protein complex]] | ||
[[Category: [Pyruvate dehydrogenase (acetyl-transferring)] kinase]] | [[Category: [Pyruvate dehydrogenase (acetyl-transferring)] kinase]] | ||
| - | [[Category: Chuang, D | + | [[Category: Chuang, D T.]] |
| - | [[Category: Chuang, J | + | [[Category: Chuang, J L.]] |
[[Category: Kato, M.]] | [[Category: Kato, M.]] | ||
| - | [[Category: Wynn, R | + | [[Category: Wynn, R M.]] |
[[Category: K]] | [[Category: K]] | ||
[[Category: LPA]] | [[Category: LPA]] | ||
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[[Category: pyruvate dehydrogenase kinase 3]] | [[Category: pyruvate dehydrogenase kinase 3]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 16:02:53 2008'' |
Revision as of 14:02, 21 February 2008
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Crystal structure of the PDK3-L2 complex
Overview
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.
About this Structure
1Y8N is a Protein complex structure of sequences from Homo sapiens with and as ligands. Active as [Pyruvate_dehydrogenase_(acetyl-transferring)_kinase [Pyruvate dehydrogenase (acetyl-transferring)] kinase], with EC number 2.7.11.2 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[[Category: [Pyruvate dehydrogenase (acetyl-transferring)] kinase]]
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