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| | ==mycobacterium diaminopimelate dicarboxylase (lysa)== | | ==mycobacterium diaminopimelate dicarboxylase (lysa)== |
| - | <StructureSection load='1hkv' size='340' side='right' caption='[[1hkv]], [[Resolution|resolution]] 2.60Å' scene=''> | + | <StructureSection load='1hkv' size='340' side='right'caption='[[1hkv]], [[Resolution|resolution]] 2.60Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[1hkv]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Myctu Myctu]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1HKV OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1HKV FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[1hkv]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Mycobacterium_tuberculosis_H37Rv Mycobacterium tuberculosis H37Rv]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1HKV OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1HKV FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=LYS:LYSINE'>LYS</scene>, <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]] 2.6Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1hkw|1hkw]]</td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=LYS:LYSINE'>LYS</scene>, <scene name='pdbligand=PLP:PYRIDOXAL-5-PHOSPHATE'>PLP</scene></td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Diaminopimelate_decarboxylase Diaminopimelate decarboxylase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=4.1.1.20 4.1.1.20] </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=1hkv FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1hkv OCA], [https://pdbe.org/1hkv PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1hkv RCSB], [https://www.ebi.ac.uk/pdbsum/1hkv PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1hkv 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=1hkv FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1hkv OCA], [http://pdbe.org/1hkv PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1hkv RCSB], [http://www.ebi.ac.uk/pdbsum/1hkv PDBsum]</span></td></tr> | + | |
| | </table> | | </table> |
| | + | == Function == |
| | + | [https://www.uniprot.org/uniprot/DCDA_MYCTU DCDA_MYCTU] Specifically catalyzes the decarboxylation of meso-diaminopimelate (meso-DAP) to L-lysine (Probable). Is essential for the viability of M.tuberculosis in the host.<ref>PMID:12637582</ref> |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
| | Check<jmol> | | Check<jmol> |
| | <jmolCheckbox> | | <jmolCheckbox> |
| - | <scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/hk/1hkv_consurf.spt"</scriptWhenChecked> | + | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/hk/1hkv_consurf.spt"</scriptWhenChecked> |
| | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> | | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> |
| | <text>to colour the structure by Evolutionary Conservation</text> | | <text>to colour the structure by Evolutionary Conservation</text> |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Diaminopimelate decarboxylase]] | + | [[Category: Large Structures]] |
| - | [[Category: Myctu]] | + | [[Category: Mycobacterium tuberculosis H37Rv]] |
| - | [[Category: Gokulan, K]] | + | [[Category: Gokulan K]] |
| - | [[Category: Jr, M S.Pavelka]] | + | [[Category: Jacobs Jr WR]] |
| - | [[Category: Jr, W R.Jacobs]] | + | [[Category: Pavelka Jr MS]] |
| - | [[Category: Rupp, B]] | + | [[Category: Rupp B]] |
| - | [[Category: Sacchettini, J C]] | + | [[Category: Sacchettini JC]] |
| - | [[Category: Structural genomic]]
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| - | [[Category: Dapdc]]
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| - | [[Category: Decarboxylase]]
| + | |
| - | [[Category: Diaminopimelate]]
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| - | [[Category: Lyase]]
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| - | [[Category: Lysine pathway]]
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| - | [[Category: Lysine synthetic pathway]]
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| - | [[Category: Mycbacterium tuberculosis]]
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| - | [[Category: Plp]]
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| - | [[Category: PSI, Protein structure initiative]]
| + | |
| - | [[Category: Pyridoxal phosphate]]
| + | |
| - | [[Category: Tb]]
| + | |
| - | [[Category: Tbsgc]]
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| Structural highlights
Function
DCDA_MYCTU Specifically catalyzes the decarboxylation of meso-diaminopimelate (meso-DAP) to L-lysine (Probable). Is essential for the viability of M.tuberculosis in the host.[1]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
The Mycobacterium tuberculosis lysA gene encodes the enzyme meso-diaminopimelate decarboxylase (DAPDC), a pyridoxal-5'-phosphate (PLP)-dependent enzyme. The enzyme catalyzes the final step in the lysine biosynthetic pathway converting meso-diaminopimelic acid (DAP) to l-lysine. The lysA gene of M. tuberculosis H37Rv has been established as essential for bacterial survival in immunocompromised mice, demonstrating that de novo biosynthesis of lysine is essential for in vivo viability. Drugs targeted against DAPDC could be efficient anti-tuberculosis drugs, and the three-dimensional structure of DAPDC from M. tuberculosis complexed with reaction product lysine and the ternary complex with PLP and lysine in the active site has been determined. The first structure of a DAPDC confirms its classification as a fold type III PLP-dependent enzyme. The structure shows a stable 2-fold dimer in head-to-tail arrangement of a triose-phosphate isomerase (TIM) barrel-like alpha/beta domain and a C-terminal beta sheet domain, similar to the ornithine decarboxylase (ODC) fold family. PLP is covalently bound via an internal aldimine, and residues from both domains and both subunits contribute to the binding pocket. Comparison of the structure with eukaryotic ODCs, in particular with a di-fluoromethyl ornithine (DMFO)-bound ODC from Trypanosoma bruceii, indicates that corresponding DAP-analogues might be potential inhibitors for mycobacterial DAPDCs.
Crystal structure of Mycobacterium tuberculosis diaminopimelate decarboxylase, an essential enzyme in bacterial lysine biosynthesis.,Gokulan K, Rupp B, Pavelka MS Jr, Jacobs WR Jr, Sacchettini JC J Biol Chem. 2003 May 16;278(20):18588-96. Epub 2003 Mar 10. PMID:12637582[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Gokulan K, Rupp B, Pavelka MS Jr, Jacobs WR Jr, Sacchettini JC. Crystal structure of Mycobacterium tuberculosis diaminopimelate decarboxylase, an essential enzyme in bacterial lysine biosynthesis. J Biol Chem. 2003 May 16;278(20):18588-96. Epub 2003 Mar 10. PMID:12637582 doi:10.1074/jbc.M301549200
- ↑ Gokulan K, Rupp B, Pavelka MS Jr, Jacobs WR Jr, Sacchettini JC. Crystal structure of Mycobacterium tuberculosis diaminopimelate decarboxylase, an essential enzyme in bacterial lysine biosynthesis. J Biol Chem. 2003 May 16;278(20):18588-96. Epub 2003 Mar 10. PMID:12637582 doi:10.1074/jbc.M301549200
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