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| | <StructureSection load='3rch' size='340' side='right'caption='[[3rch]], [[Resolution|resolution]] 2.80Å' scene=''> | | <StructureSection load='3rch' size='340' side='right'caption='[[3rch]], [[Resolution|resolution]] 2.80Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[3rch]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3RCH OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3RCH FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[3rch]] 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=3RCH OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3RCH FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=PLP:PYRIDOXAL-5-PHOSPHATE'>PLP</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]] 2.8Å</td></tr> |
| - | <tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=LLP:(2S)-2-AMINO-6-[[3-HYDROXY-2-METHYL-5-(PHOSPHONOOXYMETHYL)PYRIDIN-4-YL]METHYLIDENEAMINO]HEXANOIC+ACID'>LLP</scene></td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=LLP:(2S)-2-AMINO-6-[[3-HYDROXY-2-METHYL-5-(PHOSPHONOOXYMETHYL)PYRIDIN-4-YL]METHYLIDENEAMINO]HEXANOIC+ACID'>LLP</scene>, <scene name='pdbligand=PLP:PYRIDOXAL-5-PHOSPHATE'>PLP</scene></td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[3rbf|3rbf]], [[3rbl|3rbl]]</div></td></tr>
| + | |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">AADC ([https://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'>[https://en.wikipedia.org/wiki/Aromatic-L-amino-acid_decarboxylase Aromatic-L-amino-acid decarboxylase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=4.1.1.28 4.1.1.28] </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=3rch FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3rch OCA], [https://pdbe.org/3rch PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3rch RCSB], [https://www.ebi.ac.uk/pdbsum/3rch PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3rch ProSAT]</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=3rch FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3rch OCA], [https://pdbe.org/3rch PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3rch RCSB], [https://www.ebi.ac.uk/pdbsum/3rch PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3rch ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Disease == | | == Disease == |
| - | [[https://www.uniprot.org/uniprot/DDC_HUMAN DDC_HUMAN]] Aromatic L-amino acid decarboxylase deficiency. The disease is caused by mutations affecting the gene represented in this entry.
| + | [https://www.uniprot.org/uniprot/DDC_HUMAN DDC_HUMAN] Aromatic L-amino acid decarboxylase deficiency. The disease is caused by mutations affecting the gene represented in this entry. |
| | == Function == | | == Function == |
| - | [[https://www.uniprot.org/uniprot/DDC_HUMAN DDC_HUMAN]] Catalyzes the decarboxylation of L-3,4-dihydroxyphenylalanine (DOPA) to dopamine, L-5-hydroxytryptophan to serotonin and L-tryptophan to tryptamine.
| + | [https://www.uniprot.org/uniprot/DDC_HUMAN DDC_HUMAN] Catalyzes the decarboxylation of L-3,4-dihydroxyphenylalanine (DOPA) to dopamine, L-5-hydroxytryptophan to serotonin and L-tryptophan to tryptamine. |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Aromatic-L-amino-acid decarboxylase]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Human]]
| + | |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Cellini, B]] | + | [[Category: Borri Voltattorni C]] |
| - | [[Category: Cutruzzola, F]] | + | [[Category: Cellini B]] |
| - | [[Category: Gianni, S]] | + | [[Category: Cutruzzola F]] |
| - | [[Category: Giardina, G]] | + | [[Category: Gianni S]] |
| - | [[Category: Montioli, R]] | + | [[Category: Giardina G]] |
| - | [[Category: Paiardini, A]] | + | [[Category: Montioli R]] |
| - | [[Category: Voltattorni, C Borri]]
| + | [[Category: Paiardini A]] |
| - | [[Category: Aadc deficiency]]
| + | |
| - | [[Category: Apo enzyme]]
| + | |
| - | [[Category: Apo form]]
| + | |
| - | [[Category: Conformational change]]
| + | |
| - | [[Category: Ddc]]
| + | |
| - | [[Category: Decarboxylase]]
| + | |
| - | [[Category: Exposed]]
| + | |
| - | [[Category: Internal aldimine]]
| + | |
| - | [[Category: L-dopa]]
| + | |
| - | [[Category: Llp]]
| + | |
| - | [[Category: Lyase]]
| + | |
| - | [[Category: Open conformation]]
| + | |
| - | [[Category: Open dimer]]
| + | |
| - | [[Category: Parkinson]]
| + | |
| - | [[Category: Plp]]
| + | |
| - | [[Category: Shiff base]]
| + | |
| Structural highlights
Disease
DDC_HUMAN Aromatic L-amino acid decarboxylase deficiency. The disease is caused by mutations affecting the gene represented in this entry.
Function
DDC_HUMAN Catalyzes the decarboxylation of L-3,4-dihydroxyphenylalanine (DOPA) to dopamine, L-5-hydroxytryptophan to serotonin and L-tryptophan to tryptamine.
Publication Abstract from PubMed
DOPA decarboxylase, the dimeric enzyme responsible for the synthesis of neurotransmitters dopamine and serotonin, is involved in severe neurological diseases such as Parkinson disease, schizophrenia, and depression. Binding of the pyridoxal-5'-phosphate (PLP) cofactor to the apoenzyme is thought to represent a central mechanism for the regulation of its activity. We solved the structure of the human apoenzyme and found it exists in an unexpected open conformation: compared to the pig kidney holoenzyme, the dimer subunits move 20 A apart and the two active sites become solvent exposed. Moreover, by tuning the PLP concentration in the crystals, we obtained two more structures with different conformations of the active site. Analysis of three-dimensional data coupled to a kinetic study allows to identify the structural determinants of the open/close conformational change occurring upon PLP binding and thereby propose a model for the preferential degradation of the apoenzymes of Group II decarboxylases.
Open conformation of human DOPA decarboxylase reveals the mechanism of PLP addition to Group II decarboxylases.,Giardina G, Montioli R, Gianni S, Cellini B, Paiardini A, Voltattorni CB, Cutruzzola F Proc Natl Acad Sci U S A. 2011 Dec 20;108(51):20514-9. Epub 2011 Dec 5. PMID:22143761[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Giardina G, Montioli R, Gianni S, Cellini B, Paiardini A, Voltattorni CB, Cutruzzola F. Open conformation of human DOPA decarboxylase reveals the mechanism of PLP addition to Group II decarboxylases. Proc Natl Acad Sci U S A. 2011 Dec 20;108(51):20514-9. Epub 2011 Dec 5. PMID:22143761 doi:10.1073/pnas.1111456108
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