1zy8
From Proteopedia
(New page: 200px<br /> <applet load="1zy8" size="450" color="white" frame="true" align="right" spinBox="true" caption="1zy8, resolution 2.59Å" /> '''The crystal structu...) |
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caption="1zy8, resolution 2.59Å" /> | caption="1zy8, resolution 2.59Å" /> | ||
'''The crystal structure of dihydrolipoamide dehydrogenase and dihydrolipoamide dehydrogenase-binding protein (didomain) subcomplex of human pyruvate dehydrogenase complex.'''<br /> | '''The crystal structure of dihydrolipoamide dehydrogenase and dihydrolipoamide dehydrogenase-binding protein (didomain) subcomplex of human pyruvate dehydrogenase complex.'''<br /> | ||
==Overview== | ==Overview== | ||
| - | The dihydrolipoamide dehydrogenase-binding protein (E3BP) and the | + | The dihydrolipoamide dehydrogenase-binding protein (E3BP) and the dihydrolipoamide acetyltransferase (E2) component enzyme form the structural core of the human pyruvate dehydrogenase complex by providing the binding sites for two other component proteins, dihydrolipoamide dehydrogenase (E3) and pyruvate dehydrogenase (E1), as well as pyruvate dehydrogenase kinases and phosphatases. Despite a high similarity between the primary structures of E3BP and E2, the E3-binding domain of human E3BP is highly specific to human E3, whereas the E1-binding domain of human E2 is highly specific to human E1. In this study, we characterized binding of human E3 to the E3-binding domain of E3BP by x-ray crystallography at 2.6-angstroms resolution, and we used this structural information to interpret the specificity for selective binding. Two subunits of E3 form a single recognition site for the E3-binding domain of E3BP through their hydrophobic interface. The hydrophobic residues Pro133, Pro154, and Ile157 in the E3-binding domain of E3BP insert themselves into the surface of both E3 polypeptide chains. Numerous ionic and hydrogen bonds between the residues of three interacting polypeptide chains adjacent to the central hydrophobic patch add to the stability of the subcomplex. The specificity of pairing for human E3BP with E3 is interpreted from its subcomplex structure to be most likely due to conformational rigidity of the binding fragment of the E3-binding domain of E3BP and its exquisite amino acid match with the E3 target interface. |
==Disease== | ==Disease== | ||
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==About this Structure== | ==About this Structure== | ||
| - | 1ZY8 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 FAD as [http://en.wikipedia.org/wiki/ligand ligand]. Active as [http://en.wikipedia.org/wiki/Dihydrolipoyl_dehydrogenase Dihydrolipoyl dehydrogenase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.8.1.4 1.8.1.4] Full crystallographic information is available from [http:// | + | 1ZY8 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=FAD:'>FAD</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Active as [http://en.wikipedia.org/wiki/Dihydrolipoyl_dehydrogenase Dihydrolipoyl dehydrogenase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.8.1.4 1.8.1.4] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1ZY8 OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Protein complex]] | [[Category: Protein complex]] | ||
| - | [[Category: Ciszak, E | + | [[Category: Ciszak, E M.]] |
| - | [[Category: Hong, Y | + | [[Category: Hong, Y S.]] |
| - | [[Category: Korotchkina, L | + | [[Category: Korotchkina, L G.]] |
[[Category: Makal, A.]] | [[Category: Makal, A.]] | ||
| - | [[Category: Patel, M | + | [[Category: Patel, M S.]] |
| - | [[Category: Vettaikkorumakankauv, A | + | [[Category: Vettaikkorumakankauv, A K.]] |
[[Category: FAD]] | [[Category: FAD]] | ||
[[Category: alpha-keto acid complex]] | [[Category: alpha-keto acid complex]] | ||
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[[Category: pyruvate dehydrogenase complex]] | [[Category: pyruvate dehydrogenase complex]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 16:20:12 2008'' |
Revision as of 14:20, 21 February 2008
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The crystal structure of dihydrolipoamide dehydrogenase and dihydrolipoamide dehydrogenase-binding protein (didomain) subcomplex of human pyruvate dehydrogenase complex.
Contents |
Overview
The dihydrolipoamide dehydrogenase-binding protein (E3BP) and the dihydrolipoamide acetyltransferase (E2) component enzyme form the structural core of the human pyruvate dehydrogenase complex by providing the binding sites for two other component proteins, dihydrolipoamide dehydrogenase (E3) and pyruvate dehydrogenase (E1), as well as pyruvate dehydrogenase kinases and phosphatases. Despite a high similarity between the primary structures of E3BP and E2, the E3-binding domain of human E3BP is highly specific to human E3, whereas the E1-binding domain of human E2 is highly specific to human E1. In this study, we characterized binding of human E3 to the E3-binding domain of E3BP by x-ray crystallography at 2.6-angstroms resolution, and we used this structural information to interpret the specificity for selective binding. Two subunits of E3 form a single recognition site for the E3-binding domain of E3BP through their hydrophobic interface. The hydrophobic residues Pro133, Pro154, and Ile157 in the E3-binding domain of E3BP insert themselves into the surface of both E3 polypeptide chains. Numerous ionic and hydrogen bonds between the residues of three interacting polypeptide chains adjacent to the central hydrophobic patch add to the stability of the subcomplex. The specificity of pairing for human E3BP with E3 is interpreted from its subcomplex structure to be most likely due to conformational rigidity of the binding fragment of the E3-binding domain of E3BP and its exquisite amino acid match with the E3 target interface.
Disease
Known diseases associated with this structure: Lacticacidemia due to PDX1 deficiency OMIM:[608769], Leigh syndrome OMIM:[238331], Leukocyte adhesion deficiency OMIM:[600065], Maple syrup urine disease, type III OMIM:[238331]
About this Structure
1ZY8 is a Protein complex structure of sequences from Homo sapiens with as ligand. Active as Dihydrolipoyl dehydrogenase, with EC number 1.8.1.4 Full crystallographic information is available from OCA.
Reference
How dihydrolipoamide dehydrogenase-binding protein binds dihydrolipoamide dehydrogenase in the human pyruvate dehydrogenase complex., Ciszak EM, Makal A, Hong YS, Vettaikkorumakankauv AK, Korotchkina LG, Patel MS, J Biol Chem. 2006 Jan 6;281(1):648-55. Epub 2005 Nov 1. PMID:16263718
Page seeded by OCA on Thu Feb 21 16:20:12 2008
Categories: Dihydrolipoyl dehydrogenase | Homo sapiens | Protein complex | Ciszak, E M. | Hong, Y S. | Korotchkina, L G. | Makal, A. | Patel, M S. | Vettaikkorumakankauv, A K. | FAD | Alpha-keto acid complex | Dihydrolipoamide dehydrogenase | Dihydrolipoamide dehydrogenase binding protein | E3 | E3-binding protein | Flavin adenine dinucleotide cofactor | Human | Pyruvate dehydrogenase complex
