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| | <StructureSection load='5tem' size='340' side='right'caption='[[5tem]], [[Resolution|resolution]] 2.20Å' scene=''> | | <StructureSection load='5tem' size='340' side='right'caption='[[5tem]], [[Resolution|resolution]] 2.20Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5tem]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Vibvu Vibvu]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5TEM OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5TEM FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5tem]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Vibrio_vulnificus_CMCP6 Vibrio vulnificus CMCP6]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5TEM OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5TEM FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=NAD:NICOTINAMIDE-ADENINE-DINUCLEOTIDE'>NAD</scene>, <scene name='pdbligand=PDC:PYRIDINE-2,6-DICARBOXYLIC+ACID'>PDC</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]] 2.2Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[5tek|5tek]], [[5ten|5ten]]</div></td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=NAD:NICOTINAMIDE-ADENINE-DINUCLEOTIDE'>NAD</scene>, <scene name='pdbligand=PDC:PYRIDINE-2,6-DICARBOXYLIC+ACID'>PDC</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">dapB, VV1_0567 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=216895 VIBVU])</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_reductase 4-hydroxy-tetrahydrodipicolinate reductase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.17.1.8 1.17.1.8] </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=5tem FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5tem OCA], [https://pdbe.org/5tem PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5tem RCSB], [https://www.ebi.ac.uk/pdbsum/5tem PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5tem 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=5tem FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5tem OCA], [https://pdbe.org/5tem PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5tem RCSB], [https://www.ebi.ac.uk/pdbsum/5tem PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5tem ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[https://www.uniprot.org/uniprot/DAPB_VIBVU DAPB_VIBVU]] Catalyzes the conversion of 4-hydroxy-tetrahydrodipicolinate (HTPA) to tetrahydrodipicolinate.[HAMAP-Rule:MF_00102]
| + | [https://www.uniprot.org/uniprot/DAPB_VIBVU DAPB_VIBVU] Catalyzes the conversion of 4-hydroxy-tetrahydrodipicolinate (HTPA) to tetrahydrodipicolinate.[HAMAP-Rule:MF_00102] |
| | <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 reductase]] | |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Vibvu]] | + | [[Category: Vibrio vulnificus CMCP6]] |
| - | [[Category: Arnette, K]] | + | [[Category: Arnette K]] |
| - | [[Category: Chruszcz, M]] | + | [[Category: Chruszcz M]] |
| - | [[Category: Klapper, V]] | + | [[Category: Klapper V]] |
| - | [[Category: Mank, N]] | + | [[Category: Mank N]] |
| - | [[Category: Lysine biosynthesis]]
| + | |
| - | [[Category: Oxidoreductase]]
| + | |
| Structural highlights
Function
DAPB_VIBVU Catalyzes the conversion of 4-hydroxy-tetrahydrodipicolinate (HTPA) to tetrahydrodipicolinate.[HAMAP-Rule:MF_00102]
Publication Abstract from PubMed
BACKGROUND: The products of the lysine biosynthesis pathway, meso-diaminopimelate and lysine, are essential for bacterial survival. This paper focuses on the structural and mechanistic characterization of 4-hydroxy-tetrahydrodipicolinate reductase (DapB), which is one of the enzymes from the lysine biosynthesis pathway. DapB catalyzes the conversion of (2S, 4S)-4-hydroxy-2,3,4,5-tetrahydrodipicolinate (HTPA) to 2,3,4,5-tetrahydrodipicolinate in an NADH/NADPH dependent reaction. Genes coding for DapBs were identified as essential for many pathogenic bacteria, and therefore DapB is an interesting new target for the development of antibiotics. METHODS: We have combined experimental and computational approaches to provide novel insights into mechanism of the DapB catalyzed reaction. RESULTS: Structures of DapBs originating from Mycobacterium tuberculosis and Vibrio vulnificus in complexes with NAD(+), NADP(+), as well as with inhibitors, were determined and described. The structures determined by us, as well as currently available structures of DapBs from other bacterial species, were compared and used to elucidate a mechanism of reaction catalyzed by this group of enzymes. Several different computational methods were used to provide a detailed description of a plausible reaction mechanism. CONCLUSIONS: This is the first report presenting the detailed mechanism of reaction catalyzed by DapB. GENERAL SIGNIFICANCE: Structural data in combination with information on the reaction mechanism provide a background for development of DapB inhibitors, including transition-state analogues.
Comparative structural and mechanistic studies of 4-hydroxy-tetrahydrodipicolinate reductases from Mycobacterium tuberculosis and Vibrio vulnificus.,Pote S, Kachhap S, Mank NJ, Daneshian L, Klapper V, Pye S, Arnette AK, Shimizu LS, Borowski T, Chruszcz M Biochim Biophys Acta Gen Subj. 2021 Jan;1865(1):129750. doi:, 10.1016/j.bbagen.2020.129750. Epub 2020 Sep 24. PMID:32980502[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Pote S, Kachhap S, Mank NJ, Daneshian L, Klapper V, Pye S, Arnette AK, Shimizu LS, Borowski T, Chruszcz M. Comparative structural and mechanistic studies of 4-hydroxy-tetrahydrodipicolinate reductases from Mycobacterium tuberculosis and Vibrio vulnificus. Biochim Biophys Acta Gen Subj. 2021 Jan;1865(1):129750. doi:, 10.1016/j.bbagen.2020.129750. Epub 2020 Sep 24. PMID:32980502 doi:http://dx.doi.org/10.1016/j.bbagen.2020.129750
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