|
|
| Line 1: |
Line 1: |
| | | | |
| | ==Structural basis for recognition of L-lysine, L-ornithine, and L-2,4-diamino butyric acid by lysine cyclodeaminase== | | ==Structural basis for recognition of L-lysine, L-ornithine, and L-2,4-diamino butyric acid by lysine cyclodeaminase== |
| - | <StructureSection load='5yu4' size='340' side='right' caption='[[5yu4]], [[Resolution|resolution]] 2.14Å' scene=''> | + | <StructureSection load='5yu4' size='340' side='right'caption='[[5yu4]], [[Resolution|resolution]] 2.14Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5yu4]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/"streptomyces_pristinaespiralis"_mancy_et_al. "streptomyces pristinaespiralis" mancy et al.]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5YU4 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5YU4 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5yu4]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Streptomyces_pristinaespiralis Streptomyces pristinaespiralis]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5YU4 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5YU4 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=DAB:2,4-DIAMINOBUTYRIC+ACID'>DAB</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=NAD:NICOTINAMIDE-ADENINE-DINUCLEOTIDE'>NAD</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]] 2.144Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">pipA, SPRI_0308, SPRI_7045 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=38300 "Streptomyces pristinaespiralis" Mancy et al.])</td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=DAB:2,4-DIAMINOBUTYRIC+ACID'>DAB</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=NAD:NICOTINAMIDE-ADENINE-DINUCLEOTIDE'>NAD</scene></td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Ornithine_cyclodeaminase Ornithine cyclodeaminase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=4.3.1.12 4.3.1.12] </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=5yu4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5yu4 OCA], [https://pdbe.org/5yu4 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5yu4 RCSB], [https://www.ebi.ac.uk/pdbsum/5yu4 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5yu4 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=5yu4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5yu4 OCA], [http://pdbe.org/5yu4 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5yu4 RCSB], [http://www.ebi.ac.uk/pdbsum/5yu4 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5yu4 ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| - | <div style="background-color:#fffaf0;">
| + | == Function == |
| - | == Publication Abstract from PubMed == | + | [https://www.uniprot.org/uniprot/D9UBW0_STRPR D9UBW0_STRPR] |
| - | L-pipecolic acid is a non-protein amino acid commonly found in plants, animals, and microorganisms. It is a well-known precursor to numerous microbial secondary metabolites and pharmaceuticals, including anticancer agents, immunosuppressants, and several antibiotics. Lysine cyclodeaminase (LCD) catalyzes beta-deamination of L-lysine into L-pipecolic acid using beta-nicotinamide adenine dinucleotide as a cofactor. Expression of a human homolog of LCD, mu-crystallin, is elevated in prostate cancer patients. To understand the structural features and catalytic mechanisms of LCD, we determined the crystal structures of Streptomyces pristinaespiralis LCD (SpLCD) in (i) a binary complex with NAD(+), (ii) a ternary complex with NAD(+) and L-pipecolic acid, (iii) a ternary complex with NAD(+) and L-proline, and (iv) a ternary complex with NAD(+) and L-2,4-diamino butyric acid. The overall structure of SpLCD was similar to that of ornithine cyclodeaminase from Pseudomonas putida. In addition, SpLCD recognized L-lysine, L-ornithine, and L-2,4-diamino butyric acid despite differences in the active site, including differences in hydrogen bonding by Asp236, which corresponds with Asp228 from Pseudomonas putida ornithine cyclodeaminase. The substrate binding pocket of SpLCD allowed substrates smaller than lysine to bind, thus enabling binding to ornithine and L-2,4-diamino butyric acid. Our structural and biochemical data facilitate a detailed understanding of substrate and product recognition, thus providing evidence for a reaction mechanism for SpLCD. The proposed mechanism is unusual in that NAD(+) is initially converted into NADH and then reverted back into NAD(+) at a late stage of the reaction.
| + | |
| - | | + | |
| - | Structural Basis for Recognition of L-lysine, L-ornithine, and L-2,4-diamino Butyric Acid by Lysine Cyclodeaminase.,Min K, Yoon HJ, Matsuura A, Kim YH, Lee HH Mol Cells. 2018 Apr 30;41(4):331-341. doi: 10.14348/molcells.2018.2313. Epub 2018, Apr 5. PMID:29629557<ref>PMID:29629557</ref>
| + | |
| - | | + | |
| - | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
| + | |
| - | </div>
| + | |
| - | <div class="pdbe-citations 5yu4" style="background-color:#fffaf0;"></div>
| + | |
| - | == References ==
| + | |
| - | <references/>
| + | |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Streptomyces pristinaespiralis mancy et al]] | + | [[Category: Large Structures]] |
| - | [[Category: Ornithine cyclodeaminase]] | + | [[Category: Streptomyces pristinaespiralis]] |
| - | [[Category: Kim, Y H]] | + | [[Category: Kim YH]] |
| - | [[Category: Lee, H H]] | + | [[Category: Lee HH]] |
| - | [[Category: Matsuura, A]] | + | [[Category: Matsuura A]] |
| - | [[Category: Min, K J]] | + | [[Category: Min KJ]] |
| - | [[Category: Yoon, H J]] | + | [[Category: Yoon HJ]] |
| - | [[Category: L-lysine cyclodeaminase]]
| + | |
| - | [[Category: Lyase]]
| + | |
| - | [[Category: Streptomyces pristinaespirali]]
| + | |
