5nno - Revision history

OCA at 13:13, 15 November 2023

OCA — Wed, 15 Nov 2023 13:13:08 GMT

←Older revision		Revision as of 13:13, 15 November 2023
Line 1:		Line 1:

	==Structure of TbALDH3 complexed with NAD and AN3057 aldehyde==		==Structure of TbALDH3 complexed with NAD and AN3057 aldehyde==
-	<StructureSection load='5nno' size='340' side='right' caption='[[5nno]], [[Resolution\|resolution]] 2.50Å' scene=''>	+	<StructureSection load='5nno' size='340' side='right'caption='[[5nno]], [[Resolution\|resolution]] 2.50Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[5nno]] is a 2 chain structure with sequence from [~~http~~://en.wikipedia.org/wiki/~~Trypanosoma_(trypanozoon)_brucei~~ Trypanosoma ~~(trypanozoon)~~ brucei]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5NNO OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=5NNO FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[5nno]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Trypanosoma_brucei Trypanosoma brucei]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5NNO OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5NNO FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=92N:4-[(1-OXIDANYL-3~{H}-2,1-BENZOXABOROL-5-YL)OXY]BENZALDEHYDE'>92N</scene>, <scene name='pdbligand=NAD:NICOTINAMIDE-ADENINE-DINUCLEOTIDE'>NAD</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]] 2.5Å</td></tr>
-	~~<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[5myp\|5myp]]</td></tr>~~	+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=92N:4-[(1-OXIDANYL-3~{H}-2,1-BENZOXABOROL-5-YL)OXY]BENZALDEHYDE'>92N</scene>, <scene name='pdbligand=NAD:NICOTINAMIDE-ADENINE-DINUCLEOTIDE'>NAD</scene></td></tr>
-	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">TbgDal_VI2840,Tb427.06.3050 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=5691 Trypanosoma (Trypanozoon) brucei])</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=5nno FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5nno OCA], [https://pdbe.org/5nno PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5nno RCSB], [https://www.ebi.ac.uk/pdbsum/5nno PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5nno 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=5nno FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5nno OCA], [~~http~~://pdbe.org/5nno PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=5nno RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/5nno PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=5nno ProSAT]</span></td></tr>	+
	</table>		</table>
		+	== Function ==
		+	[https://www.uniprot.org/uniprot/C9ZQX6_TRYB9 C9ZQX6_TRYB9]
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
Line 18:		Line 19:
	</div>		</div>
	<div class="pdbe-citations 5nno" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 5nno" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Aldehyde dehydrogenase 3D structures\|Aldehyde dehydrogenase 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Field, M C]]~~	+	[[Category: Large Structures]]
-	~~[[Category: Horn, D]]~~	+
-	~~[[Category: Zhang, N]]~~	+
-	~~[[Category: Zoltner, M]]~~	+
-	~~[[Category: Aldehyde dehydrogenase]]~~	+
-	~~[[Category: Aldh]]~~	+
-	~~[[Category: Glycosomal]]~~	+
-	~~[[Category: Nad]]~~	+
-	~~[[Category: Oxaborole]]~~	+
-	~~[[Category: Oxidoreductase~~]]	+
	[[Category: Trypanosoma brucei]]		[[Category: Trypanosoma brucei]]
		+	[[Category: Field MC]]
		+	[[Category: Horn D]]
		+	[[Category: Zhang N]]
		+	[[Category: Zoltner M]]

OCA at 07:44, 22 February 2018

OCA — Thu, 22 Feb 2018 07:44:32 GMT

←Older revision		Revision as of 07:44, 22 February 2018
Line 3:		Line 3:
	<StructureSection load='5nno' size='340' side='right' caption='[[5nno]], [[Resolution\|resolution]] 2.50Å' scene=''>		<StructureSection load='5nno' size='340' side='right' caption='[[5nno]], [[Resolution\|resolution]] 2.50Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[5nno]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5NNO OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5NNO FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[5nno]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Trypanosoma_(trypanozoon)_brucei Trypanosoma (trypanozoon) brucei]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5NNO OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5NNO FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=92N:4-[(1-OXIDANYL-3~{H}-2,1-BENZOXABOROL-5-YL)OXY]BENZALDEHYDE'>92N</scene>, <scene name='pdbligand=NAD:NICOTINAMIDE-ADENINE-DINUCLEOTIDE'>NAD</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=92N:4-[(1-OXIDANYL-3~{H}-2,1-BENZOXABOROL-5-YL)OXY]BENZALDEHYDE'>92N</scene>, <scene name='pdbligand=NAD:NICOTINAMIDE-ADENINE-DINUCLEOTIDE'>NAD</scene></td></tr>
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[5myp\|5myp]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[5myp\|5myp]]</td></tr>
		+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">TbgDal_VI2840,Tb427.06.3050 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=5691 Trypanosoma (Trypanozoon) brucei])</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=5nno FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5nno OCA], [http://pdbe.org/5nno PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5nno RCSB], [http://www.ebi.ac.uk/pdbsum/5nno PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5nno 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=5nno FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5nno OCA], [http://pdbe.org/5nno PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5nno RCSB], [http://www.ebi.ac.uk/pdbsum/5nno PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5nno ProSAT]</span></td></tr>
	</table>		</table>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Recent development of benzoxaborole-based chemistry gave rise to a collection of compounds with great potential in targeting diverse infectious diseases, including human African Trypanosomiasis (HAT), a devastating neglected tropical disease. However, further medicinal development is largely restricted by a lack of insight into mechanism of action (MoA) in pathogenic kinetoplastids. We adopted a multidisciplinary approach, combining a high-throughput forward genetic screen with functional group focused chemical biological, structural biology and biochemical analyses, to tackle the complex MoAs of benzoxaboroles in Trypanosoma brucei. We describe an oxidative enzymatic pathway composed of host semicarbazide-sensitive amine oxidase and a trypanosomal aldehyde dehydrogenase TbALDH3. Two sequential reactions through this pathway serve as the key underlying mechanism for activating a series of 4-aminomethylphenoxy-benzoxaboroles as potent trypanocides; the methylamine parental compounds as pro-drugs are transformed first into intermediate aldehyde metabolites, and further into the carboxylate metabolites as effective forms. Moreover, comparative biochemical and crystallographic analyses elucidated the catalytic specificity of TbALDH3 towards the benzaldehyde benzoxaborole metabolites as xenogeneic substrates. Overall, this work proposes a novel drug activation mechanism dependent on both host and parasite metabolism of primary amine containing molecules, which contributes a new perspective to our understanding of the benzoxaborole MoA, and could be further exploited to improve the therapeutic index of antimicrobial compounds.
		+
		+	Host-parasite co-metabolic activation of antitrypanosomal aminomethyl-benzoxaboroles.,Zhang N, Zoltner M, Leung KF, Scullion P, Hutchinson S, Del Pino RC, Vincent IM, Zhang YK, Freund YR, Alley MRK, Jacobs RT, Read KD, Barrett MP, Horn D, Field MC PLoS Pathog. 2018 Feb 9;14(2):e1006850. doi: 10.1371/journal.ppat.1006850. PMID:29425238<ref>PMID:29425238</ref>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	<div class="pdbe-citations 5nno" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>

OCA: Protected "5nno" [edit=sysop:move=sysop]

OCA — Wed, 19 Apr 2017 13:03:03 GMT

Protected "5nno" [edit=sysop:move=sysop]

←Older revision

Revision as of 13:03, 19 April 2017

OCA: New page: ==Structure of TbALDH3 complexed with NAD and AN3057 aldehyde== =...

OCA — Wed, 19 Apr 2017 13:03:00 GMT

New page: ==Structure of TbALDH3 complexed with NAD and AN3057 aldehyde== <StructureSection load='5nno' size='340' side='right' caption='5nno, resolution 2.50Å' scene=''> =...

New page

==Structure of TbALDH3 complexed with NAD and AN3057 aldehyde==
<StructureSection load='5nno' size='340' side='right' caption='[[5nno]], [[Resolution|resolution]] 2.50Å' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[5nno]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5NNO OCA]. For a guided tour on the structure components use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5NNO FirstGlance]. 
</td></tr><tr id='ligand'><td class="sblockLbl">[[Ligand|Ligands:]]</td><td class="sblockDat"><scene name='pdbligand=92N:4-[(1-OXIDANYL-3~{H}-2,1-BENZOXABOROL-5-YL)OXY]BENZALDEHYDE'>92N</scene>, <scene name='pdbligand=NAD:NICOTINAMIDE-ADENINE-DINUCLEOTIDE'>NAD</scene></td></tr>
<tr id='related'><td class="sblockLbl">[[Related_structure|Related:]]</td><td class="sblockDat">[[5myp|5myp]]</td></tr>
<tr id='resources'><td class="sblockLbl">Resources:</td><td class="sblockDat">[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5nno FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5nno OCA], [http://pdbe.org/5nno PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5nno RCSB], [http://www.ebi.ac.uk/pdbsum/5nno PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5nno ProSAT]</td></tr>
</table>
__TOC__
</StructureSection>
[[Category: Field, M C]]
[[Category: Horn, D]]
[[Category: Zhang, N]]
[[Category: Zoltner, M]]
[[Category: Aldehyde dehydrogenase]]
[[Category: Aldh]]
[[Category: Glycosomal]]
[[Category: Nad]]
[[Category: Oxaborole]]
[[Category: Oxidoreductase]]
[[Category: Trypanosoma brucei]]