1zy8
From Proteopedia
| Line 4: | Line 4: | ||
|PDB= 1zy8 |SIZE=350|CAPTION= <scene name='initialview01'>1zy8</scene>, resolution 2.59Å | |PDB= 1zy8 |SIZE=350|CAPTION= <scene name='initialview01'>1zy8</scene>, resolution 2.59Å | ||
|SITE= | |SITE= | ||
| - | |LIGAND= <scene name='pdbligand=FAD:FLAVIN-ADENINE DINUCLEOTIDE'>FAD</scene> | + | |LIGAND= <scene name='pdbligand=FAD:FLAVIN-ADENINE+DINUCLEOTIDE'>FAD</scene> |
| - | |ACTIVITY= [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] | + | |ACTIVITY= <span class='plainlinks'>[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] </span> |
|GENE= DLD, GCSL, LAD, PHE3 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]), PDHX, PDX1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]) | |GENE= DLD, GCSL, LAD, PHE3 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]), PDHX, PDX1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]) | ||
| + | |DOMAIN= | ||
| + | |RELATEDENTRY=[[1ni4|1ni4]] | ||
| + | |RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1zy8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1zy8 OCA], [http://www.ebi.ac.uk/pdbsum/1zy8 PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1zy8 RCSB]</span> | ||
}} | }} | ||
| Line 14: | Line 17: | ||
==Overview== | ==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. | 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:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=608769 608769]], Leigh syndrome OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=238331 238331]], Leukocyte adhesion deficiency OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=600065 600065]], Maple syrup urine disease, type III OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=238331 238331]] | ||
==About this Structure== | ==About this Structure== | ||
| Line 32: | Line 32: | ||
[[Category: Patel, M S.]] | [[Category: Patel, M S.]] | ||
[[Category: Vettaikkorumakankauv, A K.]] | [[Category: Vettaikkorumakankauv, A K.]] | ||
| - | [[Category: FAD]] | ||
[[Category: alpha-keto acid complex]] | [[Category: alpha-keto acid complex]] | ||
[[Category: dihydrolipoamide dehydrogenase]] | [[Category: dihydrolipoamide dehydrogenase]] | ||
| Line 43: | Line 42: | ||
[[Category: pyruvate dehydrogenase complex]] | [[Category: pyruvate dehydrogenase complex]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 01:43:11 2008'' |
Revision as of 22:43, 30 March 2008
| |||||||
| , resolution 2.59Å | |||||||
|---|---|---|---|---|---|---|---|
| Ligands: | |||||||
| Gene: | DLD, GCSL, LAD, PHE3 (Homo sapiens), PDHX, PDX1 (Homo sapiens) | ||||||
| Activity: | Dihydrolipoyl dehydrogenase, with EC number 1.8.1.4 | ||||||
| Related: | 1ni4
| ||||||
| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
The crystal structure of dihydrolipoamide dehydrogenase and dihydrolipoamide dehydrogenase-binding protein (didomain) subcomplex of human pyruvate dehydrogenase complex.
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.
About this Structure
1ZY8 is a Protein complex structure of sequences from Homo sapiens. 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 Mon Mar 31 01:43:11 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. | Alpha-keto acid complex | Dihydrolipoamide dehydrogenase | Dihydrolipoamide dehydrogenase binding protein | E3 | E3-binding protein | Flavin adenine dinucleotide cofactor | Human | Pyruvate dehydrogenase complex
