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| | <StructureSection load='4cxq' size='340' side='right'caption='[[4cxq]], [[Resolution|resolution]] 1.80Å' scene=''> | | <StructureSection load='4cxq' size='340' side='right'caption='[[4cxq]], [[Resolution|resolution]] 1.80Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4cxq]] 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]. This structure supersedes the now removed PDB entry [http://oca.weizmann.ac.il/oca-bin/send-pdb?obs=1&id=4mqn 4mqn]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4CXQ OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=4CXQ FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4cxq]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Mycobacterium_tuberculosis Mycobacterium tuberculosis]. This structure supersedes the now removed PDB entry [http://oca.weizmann.ac.il/oca-bin/send-pdb?obs=1&id=4mqn 4mqn]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4CXQ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4CXQ FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=KAP:7-KETO-8-AMINOPELARGONIC+ACID'>KAP</scene>, <scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</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]] 1.8Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4cxr|4cxr]], [[4mqp|4mqp]], [[4mqq|4mqq]], [[4mqr|4mqr]]</td></tr>
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=KAP:7-KETO-8-AMINOPELARGONIC+ACID'>KAP</scene>, <scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</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/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=4cxq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4cxq OCA], [https://pdbe.org/4cxq PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4cxq RCSB], [https://www.ebi.ac.uk/pdbsum/4cxq PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4cxq ProSAT]</span></td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=4cxq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4cxq OCA], [http://pdbe.org/4cxq PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4cxq RCSB], [http://www.ebi.ac.uk/pdbsum/4cxq PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4cxq 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> |
| | <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: Adenosylmethionine--8-amino-7-oxononanoate transaminase]] | |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Aldrich, C C]] | + | [[Category: Mycobacterium tuberculosis]] |
| - | [[Category: Dai, R]] | + | [[Category: Aldrich CC]] |
| - | [[Category: Finzel, B C]] | + | [[Category: Dai R]] |
| - | [[Category: Geders, T W]] | + | [[Category: Finzel BC]] |
| - | [[Category: Wilson, D J]] | + | [[Category: Geders TW]] |
| - | [[Category: Transaminase]] | + | [[Category: Wilson DJ]] |
| - | [[Category: Transferase]]
| + | |
| - | [[Category: Tuberculosis]]
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| 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]
Publication Abstract from PubMed
7,8-Diaminopelargonic acid synthase (BioA) of Mycobacterium tuberculosis is a recently validated target for therapeutic intervention in the treatment of tuberculosis (TB). Using biophysical fragment screening and structural characterization of compounds, we have identified a potent aryl hydrazine inhibitor of BioA that reversibly modifies the pyridoxal-5'-phosphate (PLP) cofactor, forming a stable quinonoid. Analogous hydrazides also form covalent adducts that can be observed crystallographically but are incapable of inactivating the enzyme. In the X-ray crystal structures, small molecules induce unexpected conformational remodeling in the substrate binding site. We compared these conformational changes to those induced upon binding of the substrate (7-keto-8-aminopelargonic acid), and characterized the inhibition kinetics and the X-ray crystal structures of BioA with the hydrazine compound and analogues to unveil the mechanism of this reversible covalent modification.
Inhibition of Mycobacterium tuberculosis Transaminase BioA by Aryl Hydrazines and Hydrazides.,Dai R, Wilson DJ, Geders TW, Aldrich CC, Finzel BC Chembiochem. 2014 Mar 3;15(4):575-86. doi: 10.1002/cbic.201300748. Epub 2014 Jan , 31. PMID:24482078[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
- ↑ Dai R, Wilson DJ, Geders TW, Aldrich CC, Finzel BC. Inhibition of Mycobacterium tuberculosis Transaminase BioA by Aryl Hydrazines and Hydrazides. Chembiochem. 2014 Mar 3;15(4):575-86. doi: 10.1002/cbic.201300748. Epub 2014 Jan , 31. PMID:24482078 doi:http://dx.doi.org/10.1002/cbic.201300748
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