1ni4
From Proteopedia
(New page: 200px<br /> <applet load="1ni4" size="450" color="white" frame="true" align="right" spinBox="true" caption="1ni4, resolution 1.95Å" /> '''HUMAN PYRUVATE DEHY...) |
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| - | [[Image:1ni4.gif|left|200px]]<br /> | + | [[Image:1ni4.gif|left|200px]]<br /><applet load="1ni4" size="350" color="white" frame="true" align="right" spinBox="true" |
| - | <applet load="1ni4" size=" | + | |
caption="1ni4, resolution 1.95Å" /> | caption="1ni4, resolution 1.95Å" /> | ||
'''HUMAN PYRUVATE DEHYDROGENASE'''<br /> | '''HUMAN PYRUVATE DEHYDROGENASE'''<br /> | ||
==Overview== | ==Overview== | ||
| - | The derivative of vitamin B1, thiamin pyrophosphate, is a cofactor of | + | The derivative of vitamin B1, thiamin pyrophosphate, is a cofactor of enzymes performing catalysis in pathways of energy production. In alpha2beta2-heterotetrameric human pyruvate dehydrogenase, this cofactor is used to cleave the Calpha-C(=O) bond of pyruvate followed by reductive acetyl transfer to lipoyl-dihydrolipoamide acetyltransferase. The dynamic nonequivalence of two, otherwise chemically equivalent, catalytic sites has not yet been understood. To understand the mechanism of action of this enzyme, we determined the crystal structure of the holo-form of human pyruvate dehydrogenase at 1.95-A resolution. We propose a model for the flip-flop action of this enzyme through a concerted approximately 2-A shuttle-like motion of its heterodimers. Similarity of thiamin pyrophosphate binding in human pyruvate dehydrogenase with functionally related enzymes suggests that this newly defined shuttle-like motion of domains is common to the family of thiamin pyrophosphate-dependent enzymes. |
==Disease== | ==Disease== | ||
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==About this Structure== | ==About this Structure== | ||
| - | 1NI4 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 MG, K and TPP as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Pyruvate_dehydrogenase_(acetyl-transferring) Pyruvate dehydrogenase (acetyl-transferring)], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.2.4.1 1.2.4.1] Full crystallographic information is available from [http:// | + | 1NI4 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=MG:'>MG</scene>, <scene name='pdbligand=K:'>K</scene> and <scene name='pdbligand=TPP:'>TPP</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Pyruvate_dehydrogenase_(acetyl-transferring) Pyruvate dehydrogenase (acetyl-transferring)], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.2.4.1 1.2.4.1] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1NI4 OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Pyruvate dehydrogenase (acetyl-transferring)]] | [[Category: Pyruvate dehydrogenase (acetyl-transferring)]] | ||
[[Category: Ciszak, E.]] | [[Category: Ciszak, E.]] | ||
| - | [[Category: Dominiak, P | + | [[Category: Dominiak, P M.]] |
| - | [[Category: Korotchkina, L | + | [[Category: Korotchkina, L G.]] |
| - | [[Category: Patel, M | + | [[Category: Patel, M S.]] |
[[Category: Sidhu, S.]] | [[Category: Sidhu, S.]] | ||
[[Category: K]] | [[Category: K]] | ||
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[[Category: thiamin pyrophosphate]] | [[Category: thiamin pyrophosphate]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 14:06:19 2008'' |
Revision as of 12:06, 21 February 2008
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HUMAN PYRUVATE DEHYDROGENASE
Contents |
Overview
The derivative of vitamin B1, thiamin pyrophosphate, is a cofactor of enzymes performing catalysis in pathways of energy production. In alpha2beta2-heterotetrameric human pyruvate dehydrogenase, this cofactor is used to cleave the Calpha-C(=O) bond of pyruvate followed by reductive acetyl transfer to lipoyl-dihydrolipoamide acetyltransferase. The dynamic nonequivalence of two, otherwise chemically equivalent, catalytic sites has not yet been understood. To understand the mechanism of action of this enzyme, we determined the crystal structure of the holo-form of human pyruvate dehydrogenase at 1.95-A resolution. We propose a model for the flip-flop action of this enzyme through a concerted approximately 2-A shuttle-like motion of its heterodimers. Similarity of thiamin pyrophosphate binding in human pyruvate dehydrogenase with functionally related enzymes suggests that this newly defined shuttle-like motion of domains is common to the family of thiamin pyrophosphate-dependent enzymes.
Disease
Known diseases associated with this structure: Leigh syndrome, X-linked OMIM:[300502], Pyruvate dehydrogenase E1-beta deficiency OMIM:[179060], Pyruvate dehydrogenase deficiency OMIM:[300502]
About this Structure
1NI4 is a Protein complex structure of sequences from Homo sapiens with , and as ligands. Active as Pyruvate dehydrogenase (acetyl-transferring), with EC number 1.2.4.1 Full crystallographic information is available from OCA.
Reference
Structural basis for flip-flop action of thiamin pyrophosphate-dependent enzymes revealed by human pyruvate dehydrogenase., Ciszak EM, Korotchkina LG, Dominiak PM, Sidhu S, Patel MS, J Biol Chem. 2003 Jun 6;278(23):21240-6. Epub 2003 Mar 21. PMID:12651851
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