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==Mycobaterium tuberculosis transaminase BioA complexed with benzo[d]thiazole-2-carbohydrazide== | |||
<StructureSection load='4mqq' size='340' side='right' caption='[[4mqq]], [[Resolution|resolution]] 1.70Å' scene=''> | |||
{ | == Structural highlights == | ||
<table><tr><td colspan='2'>[[4mqq]] 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=4MQQ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4MQQ FirstGlance]. <br> | |||
</td></tr><tr><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=2B6:(4-{[(E)-(1,3-BENZOTHIAZOL-2-YLCARBONYL)DIAZENYL]METHYL}-5-HYDROXY-6-METHYLPYRIDIN-3-YL)METHYL+DIHYDROGEN+PHOSPHATE'>2B6</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=IMD:IMIDAZOLE'>IMD</scene><br> | |||
<tr><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4mqn|4mqn]], [[4mqo|4mqo]], [[4mqp|4mqp]], [[4mqr|4mqr]]</td></tr> | |||
<tr><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">bioA, Rv1568, MT1619, MTCY336.35c ([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><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><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4mqq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4mqq OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4mqq RCSB], [http://www.ebi.ac.uk/pdbsum/4mqq PDBsum]</span></td></tr> | |||
<table> | |||
<div style="background-color:#fffaf0;"> | |||
== 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<ref>PMID:24482078</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
== References == | |||
== | <references/> | ||
__TOC__ | |||
</StructureSection> | |||
[[Category: Adenosylmethionine--8-amino-7-oxononanoate transaminase]] | [[Category: Adenosylmethionine--8-amino-7-oxononanoate transaminase]] | ||
[[Category: Dai, R.]] | [[Category: Dai, R.]] | ||
Revision as of 15:22, 18 May 2014
Mycobaterium tuberculosis transaminase BioA complexed with benzo[d]thiazole-2-carbohydrazideMycobaterium tuberculosis transaminase BioA complexed with benzo[d]thiazole-2-carbohydrazide
Structural highlights
Publication Abstract from PubMed7,8-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[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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