2f5z
From Proteopedia
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|PDB= 2f5z |SIZE=350|CAPTION= <scene name='initialview01'>2f5z</scene>, resolution 2.18Å | |PDB= 2f5z |SIZE=350|CAPTION= <scene name='initialview01'>2f5z</scene>, resolution 2.18Å | ||
|SITE= | |SITE= | ||
| - | |LIGAND= <scene name='pdbligand= | + | |LIGAND= <scene name='pdbligand=FAD:FLAVIN-ADENINE+DINUCLEOTIDE'>FAD</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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=[[1zmc|1ZMC]], [[1zmd|1ZMD]] | ||
| + | |RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2f5z FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2f5z OCA], [http://www.ebi.ac.uk/pdbsum/2f5z PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=2f5z RCSB]</span> | ||
}} | }} | ||
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==Overview== | ==Overview== | ||
The 9.5 MDa human pyruvate dehydrogenase complex (PDC) utilizes the specific dihydrolipoamide dehydrogenase (E3) binding protein (E3BP) to tether the essential E3 component to the 60-meric core of the complex. Here, we report crystal structures of the binding domain (E3BD) of human E3BP alone and in complex with human E3 at 1.6 angstroms and 2.2 angstroms, respectively. The latter structure shows that residues from E3BD contact E3 across its 2-fold axis, resulting in one E3BD binding site on the E3 homodimer. Negligible conformational changes occur in E3BD upon its high-affinity binding to E3. Modifications of E3BD residues at the center of the E3BD/E3 interface impede E3 binding far more severely than those of residues on the periphery, validating the "hot spot" paradigm for protein interactions. A cluster of disease-causing E3 mutations located near the center of the E3BD/E3 interface prevents the efficient recruitment of these E3 variants by E3BP into the PDC, leading to the dysfunction of the PDC catalytic machine. | The 9.5 MDa human pyruvate dehydrogenase complex (PDC) utilizes the specific dihydrolipoamide dehydrogenase (E3) binding protein (E3BP) to tether the essential E3 component to the 60-meric core of the complex. Here, we report crystal structures of the binding domain (E3BD) of human E3BP alone and in complex with human E3 at 1.6 angstroms and 2.2 angstroms, respectively. The latter structure shows that residues from E3BD contact E3 across its 2-fold axis, resulting in one E3BD binding site on the E3 homodimer. Negligible conformational changes occur in E3BD upon its high-affinity binding to E3. Modifications of E3BD residues at the center of the E3BD/E3 interface impede E3 binding far more severely than those of residues on the periphery, validating the "hot spot" paradigm for protein interactions. A cluster of disease-causing E3 mutations located near the center of the E3BD/E3 interface prevents the efficient recruitment of these E3 variants by E3BP into the PDC, leading to the dysfunction of the PDC catalytic machine. | ||
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| - | ==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== | ||
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[[Category: Tomchick, D R.]] | [[Category: Tomchick, D R.]] | ||
[[Category: Wynn, R M.]] | [[Category: Wynn, R M.]] | ||
| - | [[Category: FAD]] | ||
| - | [[Category: SO4]] | ||
[[Category: protein-protein complex]] | [[Category: protein-protein 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 02:58:21 2008'' |
Revision as of 23:58, 30 March 2008
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| , resolution 2.18Å | |||||||
|---|---|---|---|---|---|---|---|
| Ligands: | , | ||||||
| Gene: | DLD, GCSL, LAD, PHE3 (Homo sapiens), PDHX, PDX1 (Homo sapiens) | ||||||
| Activity: | Dihydrolipoyl dehydrogenase, with EC number 1.8.1.4 | ||||||
| Related: | 1ZMC, 1ZMD
| ||||||
| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
Crystal Structure of Human Dihydrolipoamide Dehydrogenase (E3) Complexed to the E3-Binding Domain of Human E3-Binding Protein
Overview
The 9.5 MDa human pyruvate dehydrogenase complex (PDC) utilizes the specific dihydrolipoamide dehydrogenase (E3) binding protein (E3BP) to tether the essential E3 component to the 60-meric core of the complex. Here, we report crystal structures of the binding domain (E3BD) of human E3BP alone and in complex with human E3 at 1.6 angstroms and 2.2 angstroms, respectively. The latter structure shows that residues from E3BD contact E3 across its 2-fold axis, resulting in one E3BD binding site on the E3 homodimer. Negligible conformational changes occur in E3BD upon its high-affinity binding to E3. Modifications of E3BD residues at the center of the E3BD/E3 interface impede E3 binding far more severely than those of residues on the periphery, validating the "hot spot" paradigm for protein interactions. A cluster of disease-causing E3 mutations located near the center of the E3BD/E3 interface prevents the efficient recruitment of these E3 variants by E3BP into the PDC, leading to the dysfunction of the PDC catalytic machine.
About this Structure
2F5Z is a Protein complex structure of sequences from Homo sapiens. Full crystallographic information is available from OCA.
Reference
Structural insight into interactions between dihydrolipoamide dehydrogenase (E3) and E3 binding protein of human pyruvate dehydrogenase complex., Brautigam CA, Wynn RM, Chuang JL, Machius M, Tomchick DR, Chuang DT, Structure. 2006 Mar;14(3):611-21. Epub 2006 Jan 26. PMID:16442803
Page seeded by OCA on Mon Mar 31 02:58:21 2008
