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[[Image:1dtw.gif|left|200px]]


{{Structure
==HUMAN BRANCHED-CHAIN ALPHA-KETO ACID DEHYDROGENASE==
|PDB= 1dtw |SIZE=350|CAPTION= <scene name='initialview01'>1dtw</scene>, resolution 2.70&Aring;
<StructureSection load='1dtw' size='340' side='right'caption='[[1dtw]], [[Resolution|resolution]] 2.70&Aring;' scene=''>
|SITE=  
== Structural highlights ==
|LIGAND= <scene name='pdbligand=K:POTASSIUM+ION'>K</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=TDP:THIAMIN+DIPHOSPHATE'>TDP</scene>
<table><tr><td colspan='2'>[[1dtw]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1DTW OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1DTW FirstGlance]. <br>
|ACTIVITY= <span class='plainlinks'>[http://en.wikipedia.org/wiki/3-methyl-2-oxobutanoate_dehydrogenase_(2-methylpropanoyl-transferring) 3-methyl-2-oxobutanoate dehydrogenase (2-methylpropanoyl-transferring)], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.2.4.4 1.2.4.4] </span>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.7&#8491;</td></tr>
|GENE=
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=K:POTASSIUM+ION'>K</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=TPP:THIAMINE+DIPHOSPHATE'>TPP</scene></td></tr>
|DOMAIN=
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1dtw FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1dtw OCA], [https://pdbe.org/1dtw PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1dtw RCSB], [https://www.ebi.ac.uk/pdbsum/1dtw PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1dtw ProSAT]</span></td></tr>
|RELATEDENTRY=
</table>
|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1dtw FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1dtw OCA], [http://www.ebi.ac.uk/pdbsum/1dtw PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1dtw RCSB]</span>
== Disease ==
}}
[https://www.uniprot.org/uniprot/ODBA_HUMAN ODBA_HUMAN] Defects in BCKDHA are a cause of maple syrup urine disease type IA (MSUD1A) [MIM:[https://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:2060625</ref> <ref>PMID:8037208</ref> <ref>PMID:2703538</ref> <ref>PMID:2241958</ref> <ref>PMID:1867199</ref> <ref>PMID:1885764</ref> <ref>PMID:8161368</ref> <ref>PMID:7883996</ref>
== Function ==
[https://www.uniprot.org/uniprot/ODBA_HUMAN ODBA_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).
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
Check<jmol>
  <jmolCheckbox>
    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/dt/1dtw_consurf.spt"</scriptWhenChecked>
    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
    <text>to colour the structure by Evolutionary Conservation</text>
  </jmolCheckbox>
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=1dtw ConSurf].
<div style="clear:both"></div>


'''HUMAN BRANCHED-CHAIN ALPHA-KETO ACID DEHYDROGENASE'''
==See Also==
 
*[[2-oxoisovalerate dehydrogenase 3D structures|2-oxoisovalerate dehydrogenase 3D structures]]
 
== References ==
==Overview==
<references/>
BACKGROUND: Mutations in components of the extraordinarily large alpha-ketoacid dehydrogenase multienzyme complexes can lead to serious and often fatal disorders in humans, including maple syrup urine disease (MSUD). In order to obtain insight into the effect of mutations observed in MSUD patients, we determined the crystal structure of branched-chain alpha-ketoacid dehydrogenase (E1), the 170 kDa alpha(2)beta(2) heterotetrameric E1b component of the branched-chain alpha-ketoacid dehydrogenase multienzyme complex. RESULTS: The 2.7 A resolution crystal structure of human E1b revealed essentially the full alpha and beta polypeptide chains of the tightly packed heterotetramer. The position of two important potassium (K(+)) ions was determined. One of these ions assists a loop that is close to the cofactor to adopt the proper conformation. The second is located in the beta subunit near the interface with the small C-terminal domain of the alpha subunit. The known MSUD mutations affect the functioning of E1b by interfering with the cofactor and K(+) sites, the packing of hydrophobic cores, and the precise arrangement of residues at or near several subunit interfaces. The Tyr--&gt;Asn mutation at position 393-alpha occurs very frequently in the US population of Mennonites and is located in a unique extension of the human E1b alpha subunit, contacting the beta' subunit. CONCLUSIONS: Essentially all MSUD mutations in human E1b can be explained on the basis of the structure, with the severity of the mutations for the stability and function of the protein correlating well with the severity of the disease for the patients. The suggestion is made that small molecules with high affinity for human E1b might alleviate effects of some of the milder forms of MSUD.
__TOC__
 
</StructureSection>
==About this Structure==
1DTW is a [[Protein complex]] structure of sequences 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=1DTW OCA].
 
==Reference==
Crystal structure of human branched-chain alpha-ketoacid dehydrogenase and the molecular basis of multienzyme complex deficiency in maple syrup urine disease., AEvarsson A, Chuang JL, Wynn RM, Turley S, Chuang DT, Hol WG, Structure. 2000 Mar 15;8(3):277-91. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/10745006 10745006]
[[Category: 3-methyl-2-oxobutanoate dehydrogenase (2-methylpropanoyl-transferring)]]
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
[[Category: Protein complex]]
[[Category: Large Structures]]
[[Category: AEvarsson, A.]]
[[Category: AEvarsson A]]
[[Category: Chuang, D T.]]
[[Category: Chuang DT]]
[[Category: Chuang, J L.]]
[[Category: Chuang JL]]
[[Category: Hol, W G.J.]]
[[Category: Hol WGJ]]
[[Category: Turley, S.]]
[[Category: Turley S]]
[[Category: Wynn, R M.]]
[[Category: Wynn RM]]
[[Category: branched-chain alpha-keto acid dehydrogenase]]
[[Category: thdp-binding fold]]
 
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