1ni4
From Proteopedia
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|PDB= 1ni4 |SIZE=350|CAPTION= <scene name='initialview01'>1ni4</scene>, resolution 1.95Å | |PDB= 1ni4 |SIZE=350|CAPTION= <scene name='initialview01'>1ni4</scene>, resolution 1.95Å | ||
|SITE= | |SITE= | ||
| - | |LIGAND= <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand= | + | |LIGAND= <scene name='pdbligand=K:POTASSIUM+ION'>K</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</scene>, <scene name='pdbligand=TPP:THIAMINE+DIPHOSPHATE'>TPP</scene> |
| - | |ACTIVITY= [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] | + | |ACTIVITY= <span class='plainlinks'>[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] </span> |
|GENE= | |GENE= | ||
| + | |DOMAIN= | ||
| + | |RELATEDENTRY= | ||
| + | |RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1ni4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1ni4 OCA], [http://www.ebi.ac.uk/pdbsum/1ni4 PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1ni4 RCSB]</span> | ||
}} | }} | ||
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==Overview== | ==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. | 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. | ||
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| - | ==Disease== | ||
| - | Known diseases associated with this structure: Leigh syndrome, X-linked OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=300502 300502]], Pyruvate dehydrogenase E1-beta deficiency OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=179060 179060]], Pyruvate dehydrogenase deficiency OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=300502 300502]] | ||
==About this Structure== | ==About this Structure== | ||
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[[Category: Patel, M S.]] | [[Category: Patel, M S.]] | ||
[[Category: Sidhu, S.]] | [[Category: Sidhu, S.]] | ||
| - | [[Category: K]] | ||
| - | [[Category: MG]] | ||
| - | [[Category: TPP]] | ||
[[Category: alpha-keto acid dehydrogenase]] | [[Category: alpha-keto acid dehydrogenase]] | ||
[[Category: pyruvate]] | [[Category: pyruvate]] | ||
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[[Category: thiamin pyrophosphate]] | [[Category: thiamin pyrophosphate]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Mar 30 22:30:43 2008'' |
Revision as of 19:30, 30 March 2008
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| , resolution 1.95Å | |||||||
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| Ligands: | , , , | ||||||
| Activity: | Pyruvate dehydrogenase (acetyl-transferring), with EC number 1.2.4.1 | ||||||
| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
HUMAN PYRUVATE DEHYDROGENASE
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.
About this Structure
1NI4 is a Protein complex structure of sequences from Homo sapiens. 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
Page seeded by OCA on Sun Mar 30 22:30:43 2008
