This old version of Proteopedia is provided for student assignments while the new version is undergoing repairs. Content and edits done in this old version of Proteopedia after March 1, 2026 will eventually be lost when it is retired in about June of 2026.

Apply for new accounts at the new Proteopedia. Your logins will work in both the old and new versions.

2f5z

From Proteopedia

(Difference between revisions)

Jump to: navigation, search

Revision as of 09:15, 10 September 2015

Crystal Structure of Human Dihydrolipoamide Dehydrogenase (E3) Complexed to the E3-Binding Domain of Human E3-Binding Protein

Structural highlights

2f5z is a 15 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	,
Related:	1zmc, 1zmd, 2f60
Gene:	DLD, GCSL, LAD, PHE3 (HUMAN), PDHX, PDX1 (HUMAN)
Activity:	Dihydrolipoyl dehydrogenase, with EC number 1.8.1.4
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum

Disease

[DLDH_HUMAN] Note=Defects in DLD are involved in the development of congenital infantile lactic acidosis. Defects in DLD are a cause of maple syrup urine disease (MSUD) [MIM:248600]. MSUD is characterized by mental and physical retardation, feeding problems and a maple syrup odor to the urine. The keto acids of the branched-chain amino acids are present in the urine, resulting from a block in oxidative decarboxylation. [ODPX_HUMAN] Defects in PDHX are the cause of pyruvate dehydrogenase E3-binding protein deficiency (PDHXD) [MIM:245349].^[1]

Function

[DLDH_HUMAN] Lipoamide dehydrogenase is a component of the glycine cleavage system as well as of the alpha-ketoacid dehydrogenase complexes. Involved in the hyperactivation of spermatazoa during capacitation and in the spermatazoal acrosome reaction. [ODPX_HUMAN] Required for anchoring dihydrolipoamide dehydrogenase (E3) to the dihydrolipoamide transacetylase (E2) core of the pyruvate dehydrogenase complexes of eukaryotes. This specific binding is essential for a functional PDH complex.

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

Publication Abstract from PubMed

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.

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^[2]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Aral B, Benelli C, Ait-Ghezala G, Amessou M, Fouque F, Maunoury C, Creau N, Kamoun P, Marsac C. Mutations in PDX1, the human lipoyl-containing component X of the pyruvate dehydrogenase-complex gene on chromosome 11p1, in congenital lactic acidosis. Am J Hum Genet. 1997 Dec;61(6):1318-26. PMID:9399911 doi:S0002-9297(07)60233-X
↑ Brautigam CA, Wynn RM, Chuang JL, Machius M, Tomchick DR, Chuang DT. Structural insight into interactions between dihydrolipoamide dehydrogenase (E3) and E3 binding protein of human pyruvate dehydrogenase complex. Structure. 2006 Mar;14(3):611-21. Epub 2006 Jan 26. PMID:16442803 doi:10.1016/j.str.2006.01.001

1 Structural highlights
2 Disease
3 Function
4 Evolutionary Conservation
5 Publication Abstract from PubMed
6 See Also
7 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/2f5z"

@@ Line 2: / Line 2: @@
 <StructureSection load='2f5z' size='340' side='right' caption='[[2f5z]], [[Resolution|resolution]] 2.18&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[2f5z]] is a 15 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2F5Z OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2F5Z FirstGlance]. <br>
+<table><tr><td colspan='2'>[[2f5z]] is a 15 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2F5Z OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2F5Z FirstGlance]. <br>
 </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=FAD:FLAVIN-ADENINE+DINUCLEOTIDE'>FAD</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
 <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1zmc|1zmc]], [[1zmd|1zmd]], [[2f60|2f60]]</td></tr>
-<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">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])</td></tr>
+<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">DLD, GCSL, LAD, PHE3 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), PDHX, PDX1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
 <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><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></td></tr>
-<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><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.rcsb.org/pdb/explore.do?structureId=2f5z RCSB], [http://www.ebi.ac.uk/pdbsum/2f5z PDBsum]</span></td></tr>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><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://pdbe.org/2f5z PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2f5z RCSB], [http://www.ebi.ac.uk/pdbsum/2f5z PDBsum]</span></td></tr>
 </table>
 == Disease ==
@@ Line 31: / Line 31: @@
 From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 </div>
+<div class="pdbe-citations 2f5z" style="background-color:#fffaf0;"></div>
 ==See Also==
@@ Line 40: / Line 41: @@
 </StructureSection>
 [[Category: Dihydrolipoyl dehydrogenase]]
-[[Category: Homo sapiens]]
+[[Category: Human]]
 [[Category: Brautigam, C A]]
 [[Category: Chuang, D T]]

2f5z

From Proteopedia

Revision as of 09:15, 10 September 2015

Crystal Structure of Human Dihydrolipoamide Dehydrogenase (E3) Complexed to the E3-Binding Domain of Human E3-Binding Protein

Structural highlights

Disease

Function

Evolutionary Conservation

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

Personal tools

Navigation

Search

Toolbox