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| | ==Crystal Structure of PLP Bound 7,8-Diaminopelargonic Acid Synthase in Bacillus subtilis== | | ==Crystal Structure of PLP Bound 7,8-Diaminopelargonic Acid Synthase in Bacillus subtilis== |
| - | <StructureSection load='3dod' size='340' side='right' caption='[[3dod]], [[Resolution|resolution]] 1.90Å' scene=''> | + | <StructureSection load='3dod' size='340' side='right'caption='[[3dod]], [[Resolution|resolution]] 1.90Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[3dod]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/"vibrio_subtilis"_ehrenberg_1835 "vibrio subtilis" ehrenberg 1835]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3DOD OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3DOD FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[3dod]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Bacillus_subtilis Bacillus subtilis]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3DOD OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3DOD 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></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]] 1.9Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">bioA, BSU30230 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=1423 "Vibrio subtilis" Ehrenberg 1835])</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></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'>[https://proteopedia.org/fgij/fg.htm?mol=3dod FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3dod OCA], [https://pdbe.org/3dod PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3dod RCSB], [https://www.ebi.ac.uk/pdbsum/3dod PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3dod 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=3dod FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3dod OCA], [http://pdbe.org/3dod PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3dod RCSB], [http://www.ebi.ac.uk/pdbsum/3dod PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3dod ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/BIOK_BACSU BIOK_BACSU]] Catalyzes the transfer of the alpha-amino group from L-lysine to 7-keto-8-aminopelargonic acid (KAPA) to form 7,8-diaminopelargonic acid (DAPA). B.subtilis is the only bacterium known to utilize L-lysine as an amino donor in the biosynthesis of DAPA.<ref>PMID:15880481</ref> | + | [https://www.uniprot.org/uniprot/BIOK_BACSU BIOK_BACSU] Catalyzes the transfer of the alpha-amino group from L-lysine to 7-keto-8-aminopelargonic acid (KAPA) to form 7,8-diaminopelargonic acid (DAPA). B.subtilis is the only bacterium known to utilize L-lysine as an amino donor in the biosynthesis of DAPA.<ref>PMID:15880481</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: Vibrio subtilis ehrenberg 1835]] | + | [[Category: Bacillus subtilis]] |
| - | [[Category: Adenosylmethionine--8-amino-7-oxononanoate transaminase]] | + | [[Category: Large Structures]] |
| - | [[Category: Dey, S]] | + | [[Category: Dey S]] |
| - | [[Category: Sacchettini, J C]] | + | [[Category: Sacchettini JC]] |
| - | [[Category: Aminotransferase]]
| + | |
| - | [[Category: Biotin biosynthesis]]
| + | |
| - | [[Category: Pyridoxal phosphate]]
| + | |
| - | [[Category: S-adenosyl-l-methionine]]
| + | |
| - | [[Category: Transferase]]
| + | |
| Structural highlights
Function
BIOK_BACSU Catalyzes the transfer of the alpha-amino group from L-lysine to 7-keto-8-aminopelargonic acid (KAPA) to form 7,8-diaminopelargonic acid (DAPA). B.subtilis is the only bacterium known to utilize L-lysine as an amino donor in the biosynthesis of DAPA.[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
- ↑ Van Arsdell SW, Perkins JB, Yocum RR, Luan L, Howitt CL, Chatterjee NP, Pero JG. Removing a bottleneck in the Bacillus subtilis biotin pathway: bioA utilizes lysine rather than S-adenosylmethionine as the amino donor in the KAPA-to-DAPA reaction. Biotechnol Bioeng. 2005 Jul 5;91(1):75-83. PMID:15880481 doi:http://dx.doi.org/10.1002/bit.20488
- ↑ 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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