3rnm
From Proteopedia
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| - | + | ==The crystal structure of the subunit binding of human dihydrolipoamide transacylase (E2b) bound to human dihydrolipoamide dehydrogenase (E3)== | |
| - | + | <StructureSection load='3rnm' size='340' side='right' caption='[[3rnm]], [[Resolution|resolution]] 2.40Å' scene=''> | |
| - | + | == Structural highlights == | |
| + | <table><tr><td colspan='2'>[[3rnm]] is a 6 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=3RNM OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3RNM FirstGlance]. <br> | ||
| + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=BME:BETA-MERCAPTOETHANOL'>BME</scene>, <scene name='pdbligand=FAD:FLAVIN-ADENINE+DINUCLEOTIDE'>FAD</scene>, <scene name='pdbligand=NHE:2-[N-CYCLOHEXYLAMINO]ETHANE+SULFONIC+ACID'>NHE</scene></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]), DBT, BCATE2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</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=3rnm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3rnm OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3rnm RCSB], [http://www.ebi.ac.uk/pdbsum/3rnm PDBsum]</span></td></tr> | ||
| + | </table> | ||
| + | == Disease == | ||
| + | [[http://www.uniprot.org/uniprot/DLDH_HUMAN 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:[http://omim.org/entry/248600 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. [[http://www.uniprot.org/uniprot/ODB2_HUMAN ODB2_HUMAN]] Defects in DBT are the cause of maple syrup urine disease type 2 (MSUD2) [MIM:[http://omim.org/entry/248600 248600]]. MSUD is an autosomal recessive disorder characterized by mental and physical retardation, feeding problems, and a maple syrup odor to the urine.<ref>PMID:1847055</ref> <ref>PMID:9621512</ref> | ||
| + | == Function == | ||
| + | [[http://www.uniprot.org/uniprot/DLDH_HUMAN 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. [[http://www.uniprot.org/uniprot/ODB2_HUMAN ODB2_HUMAN]] The branched-chain alpha-keto dehydrogenase complex catalyzes the overall conversion of alpha-keto acids to acyl-CoA and CO(2). It contains multiple copies of three enzymatic components: branched-chain alpha-keto acid decarboxylase (E1), lipoamide acyltransferase (E2) and lipoamide dehydrogenase (E3). | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | The purified mammalian branched-chain alpha-ketoacid dehydrogenase complex (BCKDC), which catalyzes the oxidative decarboxylation of branched-chain alpha-keto acids, is essentially devoid of the constituent dihydrolipoamide dehydrogenase component (E3). The absence of E3 is associated with the low affinity of the subunit-binding domain of human BCKDC (hSBDb) for hE3. In this work, sequence alignments of hSBDb with the E3-binding domain (E3BD) of the mammalian pyruvate dehydrogenase complex show that hSBDb has an arginine at position 118, where E3BD features an asparagine. Substitution of Arg-118 with an asparagine increases the binding affinity of the R118N hSBDb variant (designated hSBDb*) for hE3 by nearly 2 orders of magnitude. The enthalpy of the binding reaction changes from endothermic with the wild-type hSBDb to exothermic with the hSBDb* variant. This higher affinity interaction allowed the determination of the crystal structure of the hE3/hSBDb* complex to 2.4-A resolution. The structure showed that the presence of Arg-118 poses a unique, possibly steric and/or electrostatic incompatibility that could impede E3 interactions with the wild-type hSBDb. Compared with the E3/E3BD structure, the hE3/hSBDb* structure has a smaller interfacial area. Solution NMR data corroborated the interactions of hE3 with Arg-118 and Asn-118 in wild-type hSBDb and mutant hSBDb*, respectively. The NMR results also showed that the interface between hSBDb and hE3 does not change significantly from hSBDb to hSBDb*. Taken together, our results represent a starting point for explaining the long standing enigma that the E2b core of the BCKDC binds E3 far more weakly relative to other alpha-ketoacid dehydrogenase complexes. | ||
| - | + | Structural and Thermodynamic Basis for Weak Interactions between Dihydrolipoamide Dehydrogenase and Subunit-binding Domain of the Branched-chain {alpha}-Ketoacid Dehydrogenase Complex.,Brautigam CA, Wynn RM, Chuang JL, Naik MT, Young BB, Huang TH, Chuang DT J Biol Chem. 2011 Jul 1;286(26):23476-88. Epub 2011 May 3. PMID:21543315<ref>PMID:21543315</ref> | |
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| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | + | </div> | |
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==See Also== | ==See Also== | ||
*[[Dihydrolipoamide acetyltransferase|Dihydrolipoamide acetyltransferase]] | *[[Dihydrolipoamide acetyltransferase|Dihydrolipoamide acetyltransferase]] | ||
*[[Dihydrolipoamide dehydrogenase|Dihydrolipoamide dehydrogenase]] | *[[Dihydrolipoamide dehydrogenase|Dihydrolipoamide dehydrogenase]] | ||
| - | + | == References == | |
| - | == | + | <references/> |
| - | + | __TOC__ | |
| + | </StructureSection> | ||
[[Category: Dihydrolipoyl dehydrogenase]] | [[Category: Dihydrolipoyl dehydrogenase]] | ||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
| - | [[Category: Brautigam, C A | + | [[Category: Brautigam, C A]] |
| - | [[Category: Chuang, D T | + | [[Category: Chuang, D T]] |
| - | [[Category: Chuang, J C | + | [[Category: Chuang, J C]] |
| - | [[Category: Wynn, R M | + | [[Category: Wynn, R M]] |
| - | [[Category: Young, B B | + | [[Category: Young, B B]] |
[[Category: Mitochondrion]] | [[Category: Mitochondrion]] | ||
[[Category: Oxidoreductase-protein binding complex]] | [[Category: Oxidoreductase-protein binding complex]] | ||
[[Category: Protein-protein interaction]] | [[Category: Protein-protein interaction]] | ||
[[Category: Redox protein]] | [[Category: Redox protein]] | ||
Revision as of 10:47, 19 December 2014
The crystal structure of the subunit binding of human dihydrolipoamide transacylase (E2b) bound to human dihydrolipoamide dehydrogenase (E3)
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