3tfu

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==Crystal structure of 7,8-diaminopelargonic acid synthase (BioA) from Mycobacterium tuberculosis, post-reaction complex with a 3,6-dihydropyrid-2-one heterocycle inhibitor==
==Crystal structure of 7,8-diaminopelargonic acid synthase (BioA) from Mycobacterium tuberculosis, post-reaction complex with a 3,6-dihydropyrid-2-one heterocycle inhibitor==
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<StructureSection load='3tfu' size='340' side='right' caption='[[3tfu]], [[Resolution|resolution]] 1.94&Aring;' scene=''>
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<StructureSection load='3tfu' size='340' side='right'caption='[[3tfu]], [[Resolution|resolution]] 1.94&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
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<table><tr><td colspan='2'>[[3tfu]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Mycobacterium_tuberculosis Mycobacterium tuberculosis]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3TFU OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3TFU FirstGlance]. <br>
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<table><tr><td colspan='2'>[[3tfu]] 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=3TFU OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3TFU FirstGlance]. <br>
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</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=DMS:DIMETHYL+SULFOXIDE'>DMS</scene>, <scene name='pdbligand=PL8:[5-HYDROXY-4-({[6-(3-HYDROXYPROPYL)-2-OXO-1,2-DIHYDROPYRIDIN-3-YL]AMINO}METHYL)-6-METHYLPYRIDIN-3-YL]METHYL+DIHYDROGEN+PHOSPHATE'>PL8</scene></td></tr>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.94&#8491;</td></tr>
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<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3tft|3tft]]</td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=DMS:DIMETHYL+SULFOXIDE'>DMS</scene>, <scene name='pdbligand=PL8:[5-HYDROXY-4-({[6-(3-HYDROXYPROPYL)-2-OXO-1,2-DIHYDROPYRIDIN-3-YL]AMINO}METHYL)-6-METHYLPYRIDIN-3-YL]METHYL+DIHYDROGEN+PHOSPHATE'>PL8</scene></td></tr>
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<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 Mycobacterium tuberculosis])</td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3tfu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3tfu OCA], [https://pdbe.org/3tfu PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3tfu RCSB], [https://www.ebi.ac.uk/pdbsum/3tfu PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3tfu ProSAT]</span></td></tr>
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<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>
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<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=3tfu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3tfu OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3tfu RCSB], [http://www.ebi.ac.uk/pdbsum/3tfu PDBsum]</span></td></tr>
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</table>
</table>
== Function ==
== Function ==
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[[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>
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[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>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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BioA catalyzes the second step of biotin biosynthesis, and this enzyme represents a potential target to develop new antitubercular agents. Herein we report the design, synthesis, and biochemical characterization of a mechanism-based inhibitor (1) featuring a 3,6-dihydropyrid-2-one heterocycle that covalently modifies the pyridoxal 5'-phosphate (PLP) cofactor of BioA through aromatization. The structure of the PLP adduct was confirmed by MS/MS and X-ray crystallography at 1.94 A resolution. Inactivation of BioA by 1 was time- and concentration-dependent and protected by substrate. We used a conditional knock-down mutant of M. tuberculosis to demonstrate the antitubercular activity of 1 correlated with BioA expression, and these results provide support for the designed mechanism of action.
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Mechanism-based Inactivation by Aromatization of the Transaminase BioA Involved in Biotin Biosynthesis in Mycobaterium tuberculosis.,Shi C, Geders TW, Park SW, Wilson DJ, Boshoff HI, Abayomi O, Barry CE, Schnappinger D, Finzel BC, Aldrich CC J Am Chem Soc. 2011 Nov 16;133(45):18194-201. Epub 2011 Oct 24. PMID:21988601<ref>PMID:21988601</ref>
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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</div>
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==See Also==
==See Also==
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*[[7%2C8-diaminopelargonic acid synthetase|7%2C8-diaminopelargonic acid synthetase]]
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*[[7%2C8-diaminopelargonic acid synthase 3D structures|7%2C8-diaminopelargonic acid synthase 3D structures]]
== References ==
== References ==
<references/>
<references/>
__TOC__
__TOC__
</StructureSection>
</StructureSection>
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[[Category: Adenosylmethionine--8-amino-7-oxononanoate transaminase]]
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[[Category: Large Structures]]
[[Category: Mycobacterium tuberculosis]]
[[Category: Mycobacterium tuberculosis]]
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[[Category: Finzel, B C]]
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[[Category: Finzel BC]]
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[[Category: Geders, T W]]
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[[Category: Geders TW]]
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[[Category: Transferase]]
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[[Category: Transferase-transferase inhibitor complex]]
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Current revision

Crystal structure of 7,8-diaminopelargonic acid synthase (BioA) from Mycobacterium tuberculosis, post-reaction complex with a 3,6-dihydropyrid-2-one heterocycle inhibitor

PDB ID 3tfu

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