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| | <StructureSection load='2bew' size='340' side='right'caption='[[2bew]], [[Resolution|resolution]] 1.79Å' scene=''> | | <StructureSection load='2bew' size='340' side='right'caption='[[2bew]], [[Resolution|resolution]] 1.79Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[2bew]] is a 3 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=2BEW OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2BEW FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[2bew]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Synthetic_construct Synthetic construct]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2BEW OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2BEW FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=K:POTASSIUM+ION'>K</scene>, <scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</scene>, <scene name='pdbligand=THW:C2-1-HYDROXYPHENYL-THIAMIN+DIPHOSPHATE'>THW</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.79Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1dtw|1dtw]], [[1ols|1ols]], [[1olu|1olu]], [[1olx|1olx]], [[1u5b|1u5b]], [[1v11|1v11]], [[1v16|1v16]], [[1v1m|1v1m]], [[1v1r|1v1r]], [[1wci|1wci]], [[1x7w|1x7w]], [[1x7x|1x7x]], [[1x7y|1x7y]], [[1x7z|1x7z]], [[1x80|1x80]], [[2beu|2beu]], [[2bev|2bev]], [[2bfb|2bfb]], [[2bfc|2bfc]], [[2bfd|2bfd]], [[2bfe|2bfe]], [[2bff|2bff]]</td></tr>
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=K:POTASSIUM+ION'>K</scene>, <scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</scene>, <scene name='pdbligand=THW:C2-1-HYDROXYPHENYL-THIAMIN+DIPHOSPHATE'>THW</scene></td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><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='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2bew FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2bew OCA], [https://pdbe.org/2bew PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2bew RCSB], [https://www.ebi.ac.uk/pdbsum/2bew PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2bew ProSAT]</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=2bew FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2bew OCA], [http://pdbe.org/2bew PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2bew RCSB], [http://www.ebi.ac.uk/pdbsum/2bew PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2bew ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Disease == | | == Disease == |
| - | [[http://www.uniprot.org/uniprot/ODBA_HUMAN ODBA_HUMAN]] Defects in BCKDHA are a cause of maple syrup urine disease type IA (MSUD1A) [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: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> [[http://www.uniprot.org/uniprot/ODBB_HUMAN ODBB_HUMAN]] Defects in BCKDHB are the cause of maple syrup urine disease type IB (MSUD1B) [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:8161368</ref> <ref>PMID:11509994</ref> <ref>PMID:22326532</ref> | + | [https://www.uniprot.org/uniprot/ODBB_HUMAN ODBB_HUMAN] Defects in BCKDHB are the cause of maple syrup urine disease type IB (MSUD1B) [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:8161368</ref> <ref>PMID:11509994</ref> <ref>PMID:22326532</ref> |
| | == Function == | | == Function == |
| - | [[http://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). [[http://www.uniprot.org/uniprot/ODBB_HUMAN ODBB_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). | + | [https://www.uniprot.org/uniprot/ODBB_HUMAN ODBB_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 == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Brautigam, C A]] | + | [[Category: Synthetic construct]] |
| - | [[Category: Chuang, D T]] | + | [[Category: Brautigam CA]] |
| - | [[Category: Chuang, J L]] | + | [[Category: Chuang DT]] |
| - | [[Category: Machius, M]] | + | [[Category: Chuang JL]] |
| - | [[Category: Tomchick, D R]] | + | [[Category: Machius M]] |
| - | [[Category: Wynn, R M]]
| + | [[Category: Tomchick DR]] |
| - | [[Category: Conformational switch]] | + | [[Category: Wynn RM]] |
| - | [[Category: Maple syrup urine disease]] | + | |
| - | [[Category: Oxidative decarboxylation]]
| + | |
| - | [[Category: Oxidoreductase]]
| + | |
| - | [[Category: Phosphorylation]]
| + | |
| - | [[Category: Thiamine diphosphate]]
| + | |
| Structural highlights
2bew is a 3 chain structure with sequence from Homo sapiens and Synthetic construct. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
| | Method: | X-ray diffraction, Resolution 1.79Å |
| Ligands: | , , , , |
| Resources: | FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT |
Disease
ODBB_HUMAN Defects in BCKDHB are the cause of maple syrup urine disease type IB (MSUD1B) [MIM:248600. MSUD is an autosomal recessive disorder characterized by mental and physical retardation, feeding problems, and a maple syrup odor to the urine.[1] [2] [3]
Function
ODBB_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
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 dehydrogenase/decarboxylase (E1b) component of the 4 MD human branched-chain alpha-ketoacid dehydrogenase complex (BCKDC) is a thiamin diphosphate (ThDP)-dependent enzyme. We have determined the crystal structures of E1b with ThDP bound intermediates after decarboxylation of alpha-ketoacids. We show that a key tyrosine residue in the E1b active site functions as a conformational switch to reduce the reactivity of the ThDP cofactor through interactions with its thiazolium ring. The intermediates do not assume the often-postulated enamine state, but likely a carbanion state. The carbanion presumably facilitates the second E1b-catalyzed reaction, involving the transfer of an acyl moiety from the intermediate to a lipoic acid prosthetic group in the transacylase (E2b) component of the BCKDC. The tyrosine switch further remodels an E1b loop region to promote E1b binding to E2b. Our results illustrate the versatility of the tyrosine switch in coordinating the catalytic events in E1b by modulating the reactivity of reaction intermediates.
A versatile conformational switch regulates reactivity in human branched-chain alpha-ketoacid dehydrogenase.,Machius M, Wynn RM, Chuang JL, Li J, Kluger R, Yu D, Tomchick DR, Brautigam CA, Chuang DT Structure. 2006 Feb;14(2):287-98. PMID:16472748[4]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Nobukuni Y, Mitsubuchi H, Hayashida Y, Ohta K, Indo Y, Ichiba Y, Endo F, Matsuda I. Heterogeneity of mutations in maple syrup urine disease (MSUD): screening and identification of affected E1 alpha and E1 beta subunits of the branched-chain alpha-keto-acid dehydrogenase multienzyme complex. Biochim Biophys Acta. 1993 Nov 25;1225(1):64-70. PMID:8161368
- ↑ Edelmann L, Wasserstein MP, Kornreich R, Sansaricq C, Snyderman SE, Diaz GA. Maple syrup urine disease: identification and carrier-frequency determination of a novel founder mutation in the Ashkenazi Jewish population. Am J Hum Genet. 2001 Oct;69(4):863-8. Epub 2001 Aug 16. PMID:11509994 doi:S0002-9297(07)61141-0
- ↑ Wang YP, Qi ML, Li TT, Zhao YJ. Two novel mutations in the BCKDHB gene (R170H, Q346R) cause the classic form of maple syrup urine disease (MSUD). Gene. 2012 Apr 25;498(1):112-5. doi: 10.1016/j.gene.2012.01.082. Epub 2012 Feb 3. PMID:22326532 doi:10.1016/j.gene.2012.01.082
- ↑ Machius M, Wynn RM, Chuang JL, Li J, Kluger R, Yu D, Tomchick DR, Brautigam CA, Chuang DT. A versatile conformational switch regulates reactivity in human branched-chain alpha-ketoacid dehydrogenase. Structure. 2006 Feb;14(2):287-98. PMID:16472748 doi:10.1016/j.str.2005.10.009
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