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| | <StructureSection load='6vvi' size='340' side='right'caption='[[6vvi]], [[Resolution|resolution]] 2.15Å' scene=''> | | <StructureSection load='6vvi' size='340' side='right'caption='[[6vvi]], [[Resolution|resolution]] 2.15Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[6vvi]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Arath Arath]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6VVI OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6VVI FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6vvi]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Arabidopsis_thaliana Arabidopsis thaliana]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6VVI OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6VVI FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</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]] 2.145Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">DHDPS1, DHDPS, DHPS1, At3g60880, T4C21_290 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=3702 ARATH])</td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/4-hydroxy-tetrahydrodipicolinate_synthase 4-hydroxy-tetrahydrodipicolinate synthase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=4.3.3.7 4.3.3.7] </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=6vvi FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6vvi OCA], [https://pdbe.org/6vvi PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6vvi RCSB], [https://www.ebi.ac.uk/pdbsum/6vvi PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6vvi 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=6vvi FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6vvi OCA], [https://pdbe.org/6vvi PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6vvi RCSB], [https://www.ebi.ac.uk/pdbsum/6vvi PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6vvi ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[https://www.uniprot.org/uniprot/DAPA1_ARATH DAPA1_ARATH]] Catalyzes the condensation of (S)-aspartate-beta-semialdehyde [(S)-ASA] and pyruvate to 4-hydroxy-tetrahydrodipicolinate (HTPA).
| + | [https://www.uniprot.org/uniprot/DAPA1_ARATH DAPA1_ARATH] Catalyzes the condensation of (S)-aspartate-beta-semialdehyde [(S)-ASA] and pyruvate to 4-hydroxy-tetrahydrodipicolinate (HTPA). |
| | <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: 4-hydroxy-tetrahydrodipicolinate synthase]] | + | [[Category: Arabidopsis thaliana]] |
| - | [[Category: Arath]]
| + | |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Hall, C J]] | + | [[Category: Hall CJ]] |
| - | [[Category: Lee, M]] | + | [[Category: Lee M]] |
| - | [[Category: Dihydrodipicolinate synthase]]
| + | |
| - | [[Category: Lyase]]
| + | |
| Structural highlights
Function
DAPA1_ARATH Catalyzes the condensation of (S)-aspartate-beta-semialdehyde [(S)-ASA] and pyruvate to 4-hydroxy-tetrahydrodipicolinate (HTPA).
Publication Abstract from PubMed
Lysine biosynthesis in plants occurs via the diaminopimelate pathway. The first committed and rate-limiting step of this pathway is catalysed by dihydrodipicolinate synthase (DHDPS), which is allosterically regulated by the end product, l-lysine (lysine). Given that lysine is a common nutritionally limiting amino acid in cereal crops, there has been much interest in probing the regulation of DHDPS. Interestingly, knockouts in Arabidopsis thaliana of each isoform (AtDHDPS1 and AtDHDPS2) result in different phenotypes, despite the enzymes sharing > 85% protein sequence identity. Accordingly, in this study, we compared the catalytic activity, lysine-mediated inhibition and structures of both A. thaliana DHDPS isoforms. We found that although the recombinantly produced enzymes have similar kinetic properties, AtDHDPS1 is 10-fold more sensitive to lysine. We subsequently used X-ray crystallography to probe for structural differences between the apo- and lysine-bound isoforms that could account for the differential allosteric inhibition. Despite no significant changes in the overall structures of the active or allosteric sites, we noted differences in the rotamer conformation of a key allosteric site residue (Trp116) and proposed that this could result in differences in lysine dissociation. Microscale thermophoresis studies supported our hypothesis, with AtDHDPS1 having a ~ 6-fold tighter lysine dissociation constant compared to AtDHDPS2, which agrees with the lower half minimal inhibitory concentration for lysine observed. Thus, we highlight that subtle differences in protein structures, which could not have been predicted from the primary sequences, can have profound effects on the allostery of a key enzyme involved in lysine biosynthesis in plants. DATABASES: Structures described are available in the Protein Data Bank under the accession numbers 6VVH and 6VVI.
Differential lysine-mediated allosteric regulation of plant dihydrodipicolinate synthase isoforms.,Hall CJ, Lee M, Boarder MP, Mangion AM, Gendall AR, Panjikar S, Perugini MA, Soares da Costa TP FEBS J. 2021 Aug;288(16):4973-4986. doi: 10.1111/febs.15766. Epub 2021 Mar 2. PMID:33586321[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Hall CJ, Lee M, Boarder MP, Mangion AM, Gendall AR, Panjikar S, Perugini MA, Soares da Costa TP. Differential lysine-mediated allosteric regulation of plant dihydrodipicolinate synthase isoforms. FEBS J. 2021 Aug;288(16):4973-4986. doi: 10.1111/febs.15766. Epub 2021 Mar 2. PMID:33586321 doi:http://dx.doi.org/10.1111/febs.15766
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