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| | <StructureSection load='5txt' size='340' side='right'caption='[[5txt]], [[Resolution|resolution]] 2.70Å' scene=''> | | <StructureSection load='5txt' size='340' side='right'caption='[[5txt]], [[Resolution|resolution]] 2.70Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5txt]] is a 6 chain structure with sequence from [http://en.wikipedia.org/wiki/Baker's_yeast Baker's yeast]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5TXT OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5TXT FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5txt]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Saccharomyces_cerevisiae_S288C Saccharomyces cerevisiae S288C]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5TXT OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5TXT FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=PE3:3,6,9,12,15,18,21,24,27,30,33,36,39-TRIDECAOXAHENTETRACONTANE-1,41-DIOL'>PE3</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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]] 2.7Å</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=PE3:3,6,9,12,15,18,21,24,27,30,33,36,39-TRIDECAOXAHENTETRACONTANE-1,41-DIOL'>PE3</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">[[5txr|5txr]]</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=5txt FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5txt OCA], [https://pdbe.org/5txt PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5txt RCSB], [https://www.ebi.ac.uk/pdbsum/5txt PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5txt ProSAT]</span></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">HEM1, CYD1, YDR232W, YD9934.16 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=559292 Baker's yeast])</td></tr>
| + | |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/5-aminolevulinate_synthase 5-aminolevulinate synthase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.3.1.37 2.3.1.37] </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=5txt FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5txt OCA], [http://pdbe.org/5txt PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5txt RCSB], [http://www.ebi.ac.uk/pdbsum/5txt PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5txt ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/HEM1_YEAST HEM1_YEAST]] Catalyzes the synthesis of 5-aminolevulinate (ALA) from succinyl-CoA and glycine, the first and rate-limiting step in heme biosynthesis.<ref>PMID:6381051</ref> | + | [https://www.uniprot.org/uniprot/HEM1_YEAST HEM1_YEAST] Catalyzes the synthesis of 5-aminolevulinate (ALA) from succinyl-CoA and glycine, the first and rate-limiting step in heme biosynthesis.<ref>PMID:6381051</ref> |
| - | <div style="background-color:#fffaf0;">
| + | |
| - | == Publication Abstract from PubMed ==
| + | |
| - | 5-Aminolevulinic acid synthase (ALAS) catalyzes the first step in heme biosynthesis. We present the crystal structure of a eukaryotic ALAS from Saccharomyces cerevisiae. In this homodimeric structure, one ALAS subunit contains covalently bound cofactor, pyridoxal 5'-phosphate (PLP), whereas the second is PLP free. Comparison between the subunits reveals PLP-coupled reordering of the active site and of additional regions to achieve the active conformation of the enzyme. The eukaryotic C-terminal extension, a region altered in multiple human disease alleles, wraps around the dimer and contacts active-site-proximal residues. Mutational analysis demonstrates that this C-terminal region that engages the active site is important for ALAS activity. Our discovery of structural elements that change conformation upon PLP binding and of direct contact between the C-terminal extension and the active site thus provides a structural basis for investigation of disruptions in the first step of heme biosynthesis and resulting human disorders.
| + | |
| - | | + | |
| - | Structure of the Mitochondrial Aminolevulinic Acid Synthase, a Key Heme Biosynthetic Enzyme.,Brown BL, Kardon JR, Sauer RT, Baker TA Structure. 2018 Apr 3;26(4):580-589.e4. doi: 10.1016/j.str.2018.02.012. Epub 2018, Mar 15. PMID:29551290<ref>PMID:29551290</ref>
| + | |
| - | | + | |
| - | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
| + | |
| - | </div>
| + | |
| - | <div class="pdbe-citations 5txt" style="background-color:#fffaf0;"></div>
| + | |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: 5-aminolevulinate synthase]] | |
| - | [[Category: Baker's yeast]] | |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Baker, T A]] | + | [[Category: Saccharomyces cerevisiae S288C]] |
| - | [[Category: Brown, B L]] | + | [[Category: Baker TA]] |
| - | [[Category: Grant, R A]] | + | [[Category: Brown BL]] |
| - | [[Category: Kardon, J R]] | + | [[Category: Grant RA]] |
| - | [[Category: Sauer, R T]] | + | [[Category: Kardon JR]] |
| - | [[Category: 5-aminolevulinic acid]] | + | [[Category: Sauer RT]] |
| - | [[Category: Heme biosynthesis]]
| + | |
| - | [[Category: Pyridoxal 5-phosphate]]
| + | |
| - | [[Category: Transferase]]
| + | |
