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| | ==Crystal structure of Mycobacterium tuberculosis 7,8-diaminopelargonic acid synthase in complex with substrate analog sinefungin== | | ==Crystal structure of Mycobacterium tuberculosis 7,8-diaminopelargonic acid synthase in complex with substrate analog sinefungin== |
| - | <StructureSection load='3lv2' size='340' side='right' caption='[[3lv2]], [[Resolution|resolution]] 2.18Å' scene=''> | + | <StructureSection load='3lv2' size='340' side='right'caption='[[3lv2]], [[Resolution|resolution]] 2.18Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[3lv2]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/"bacillus_tuberculosis"_(zopf_1883)_klein_1884 "bacillus tuberculosis" (zopf 1883) klein 1884]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3LV2 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3LV2 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[3lv2]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Mycobacterium_tuberculosis Mycobacterium tuberculosis]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3LV2 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3LV2 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=PLP:PYRIDOXAL-5-PHOSPHATE'>PLP</scene>, <scene name='pdbligand=SFG:SINEFUNGIN'>SFG</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]] 2.18Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3bv0|3bv0]]</td></tr>
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=PLP:PYRIDOXAL-5-PHOSPHATE'>PLP</scene>, <scene name='pdbligand=SFG:SINEFUNGIN'>SFG</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">bioA, MT1619, MTCY336.35c, Rv1568 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=1773 "Bacillus tuberculosis" (Zopf 1883) Klein 1884])</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=3lv2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3lv2 OCA], [https://pdbe.org/3lv2 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3lv2 RCSB], [https://www.ebi.ac.uk/pdbsum/3lv2 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3lv2 ProSAT]</span></td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Adenosylmethionine--8-amino-7-oxononanoate_transaminase Adenosylmethionine--8-amino-7-oxononanoate transaminase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.6.1.62 2.6.1.62] </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=3lv2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3lv2 OCA], [http://pdbe.org/3lv2 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3lv2 RCSB], [http://www.ebi.ac.uk/pdbsum/3lv2 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3lv2 ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/BIOA_MYCTU BIOA_MYCTU]] Catalyzes the reversible transfer of the alpha-amino group from S-adenosyl-L-methionine (SAM) to 7-keto-8-aminopelargonic acid (KAPA) to form 7,8-diaminopelargonic acid (DAPA). It is the only animotransferase known to utilize SAM as an amino donor. Can also use sinefungin as substrate.<ref>PMID:16984394</ref> | + | [https://www.uniprot.org/uniprot/BIOA_MYCTU BIOA_MYCTU] Catalyzes the reversible transfer of the alpha-amino group from S-adenosyl-L-methionine (SAM) to 7-keto-8-aminopelargonic acid (KAPA) to form 7,8-diaminopelargonic acid (DAPA). It is the only animotransferase known to utilize SAM as an amino donor. Can also use sinefungin as substrate.<ref>PMID:16984394</ref> |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
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| | ==See Also== | | ==See Also== |
| - | *[[7%2C8-diaminopelargonic acid synthetase|7%2C8-diaminopelargonic acid synthetase]] | + | *[[7%2C8-diaminopelargonic acid synthase 3D structures|7%2C8-diaminopelargonic acid synthase 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Adenosylmethionine--8-amino-7-oxononanoate transaminase]] | + | [[Category: Large Structures]] |
| - | [[Category: Dey, S]] | + | [[Category: Mycobacterium tuberculosis]] |
| - | [[Category: Sacchettini, J C]]
| + | [[Category: Dey S]] |
| - | [[Category: 8-diaminopelargonic acid synthase]]
| + | [[Category: Sacchettini JC]] |
| - | [[Category: Aminotransferase]]
| + | |
| - | [[Category: Bioa]]
| + | |
| - | [[Category: Biotin biosynthesis]]
| + | |
| - | [[Category: Pyridoxal phosphate]]
| + | |
| - | [[Category: Rv1568]]
| + | |
| - | [[Category: S-adenosyl-l-methionine]] | + | |
| - | [[Category: Transferase]] | + | |
| Structural highlights
Function
BIOA_MYCTU Catalyzes the reversible transfer of the alpha-amino group from S-adenosyl-L-methionine (SAM) to 7-keto-8-aminopelargonic acid (KAPA) to form 7,8-diaminopelargonic acid (DAPA). It is the only animotransferase known to utilize SAM as an amino donor. Can also use sinefungin as substrate.[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
Mycobacterium tuberculosis (Mtb) depends on biotin synthesis for survival during infection. In the absence of biotin, disruption of the biotin biosynthesis pathway results in cell death rather than growth arrest, an unusual phenotype for an Mtb auxotroph. Humans lack the enzymes for biotin production, making the proteins of this essential Mtb pathway promising drug targets. To this end, we have determined the crystal structures of the second and third enzymes of the Mtb biotin biosynthetic pathway, 7,8-diaminopelargonic acid synthase (DAPAS) and dethiobiotin synthetase (DTBS), at respective resolutions of 2.2 and 1.85 A. Superimposition of the DAPAS structures bound either to the SAM analogue sinefungin or to 7-keto-8-aminopelargonic acid (KAPA) allowed us to map the putative binding site for the substrates and to propose a mechanism by which the enzyme accommodates their disparate structures. Comparison of the DTBS structures bound to the substrate 7,8-diaminopelargonic acid (DAPA) or to ADP and the product dethiobiotin (DTB) permitted derivation of an enzyme mechanism. There are significant differences between the Mtb enzymes and those of other organisms; the Bacillus subtilis DAPAS, presented here at a high resolution of 2.2 A, has active site variations and the Escherichia coli and Helicobacter pylori DTBS have alterations in their overall folds. We have begun to exploit the unique characteristics of the Mtb structures to design specific inhibitors against the biotin biosynthesis pathway in Mtb.
Structural characterization of the Mycobacterium tuberculosis biotin biosynthesis enzymes 7,8-diaminopelargonic acid synthase and dethiobiotin synthetase .,Dey S, Lane JM, Lee RE, Rubin EJ, Sacchettini JC Biochemistry. 2010 Aug 10;49(31):6746-60. PMID:20565114[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Mann S, Ploux O. 7,8-Diaminoperlargonic acid aminotransferase from Mycobacterium tuberculosis, a potential therapeutic target. Characterization and inhibition studies. FEBS J. 2006 Oct;273(20):4778-89. Epub 2006 Sep 19. PMID:16984394 doi:10.1111/j.1742-4658.2006.05479.x
- ↑ Dey S, Lane JM, Lee RE, Rubin EJ, Sacchettini JC. Structural characterization of the Mycobacterium tuberculosis biotin biosynthesis enzymes 7,8-diaminopelargonic acid synthase and dethiobiotin synthetase . Biochemistry. 2010 Aug 10;49(31):6746-60. PMID:20565114 doi:10.1021/bi902097j
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