4i73 - Revision history

OCA at 08:46, 9 November 2022

OCA — Wed, 09 Nov 2022 08:46:08 GMT

←Older revision		Revision as of 08:46, 9 November 2022
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	==Crystal structure of the Trypanosoma brucei Inosine-Adenosine-Guanosine nucleoside hydrolase in complex with compound UAMC-00312==		==Crystal structure of the Trypanosoma brucei Inosine-Adenosine-Guanosine nucleoside hydrolase in complex with compound UAMC-00312==
-	<StructureSection load='4i73' size='340' side='right' caption='[[4i73]], [[Resolution\|resolution]] 2.18Å' scene=''>	+	<StructureSection load='4i73' size='340' side='right'caption='[[4i73]], [[Resolution\|resolution]] 2.18Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[4i73]] is a 4 chain structure with sequence from [~~http~~://en.wikipedia.org/wiki/~~Tryb2 Tryb2~~]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4I73 OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=4I73 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[4i73]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Trypanosoma_brucei_brucei_TREU927 Trypanosoma brucei brucei TREU927]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4I73 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4I73 FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=MBY:(2R,3R,4S)-2-(HYDROXYMETHYL)-1-[(4-HYDROXYTHIENO[3,2-D]PYRIMIDIN-7-YL)METHYL]PYRROLIDINE-3,4-DIOL'>MBY</scene>, <scene name='pdbligand=NI:NICKEL+(II)+ION'>NI</scene~~></td></tr>~~	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=MBY:(2R,3R,4S)-2-(HYDROXYMETHYL)-1-[(4-HYDROXYTHIENO[3,2-D]PYRIMIDIN-7-YL)METHYL]PYRROLIDINE-3,4-DIOL'>MBY</scene>, <scene name='pdbligand=NI:NICKEL+(II)+ION'>NI</scene></td></tr>
-	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[3epw\|3epw]], [[3fz0\|3fz0]], [[4i70\|4i70]], [[4i71\|4i71]], [[4i72\|4i72]], [[4i74\|4i74]], [[4i75\|4i75]]</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=4i73 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4i73 OCA], [https://pdbe.org/4i73 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4i73 RCSB], [https://www.ebi.ac.uk/pdbsum/4i73 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4i73 ProSAT]</span></td></tr>
-	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">Tb927.3.2960 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=999953 TRYB2])</td></tr>	+
-	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Purine_nucleosidase Purine nucleosidase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.2.2.1 3.2.2.1] </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=4i73 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4i73 OCA], [~~http~~://pdbe.org/4i73 PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=4i73 RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/4i73 PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=4i73 ProSAT]</span></td></tr>	+
	</table>		</table>
		+	== Function ==
		+	[https://www.uniprot.org/uniprot/Q57ZL6_TRYB2 Q57ZL6_TRYB2]
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
Line 23:		Line 22:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Purine nucleosidase~~]]	+	[[Category: Large Structures]]
-	[[Category: ~~Tryb2~~]]	+	[[Category: Trypanosoma brucei brucei TREU927]]
-	[[Category: Degano, M]]	+	[[Category: Degano M]]
-	[[Category: Giannese, F]]	+	[[Category: Giannese F]]
-	~~[[Category: Hydrolase-hydrolase inhibitor complex]]~~	+
-	~~[[Category: Nh fold]]~~	+
-	~~[[Category: Nucleoside hydrolase~~]]	+

OCA at 22:45, 5 August 2016

OCA — Fri, 05 Aug 2016 22:45:36 GMT

←Older revision		Revision as of 22:45, 5 August 2016
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		+
	==Crystal structure of the Trypanosoma brucei Inosine-Adenosine-Guanosine nucleoside hydrolase in complex with compound UAMC-00312==		==Crystal structure of the Trypanosoma brucei Inosine-Adenosine-Guanosine nucleoside hydrolase in complex with compound UAMC-00312==
	<StructureSection load='4i73' size='340' side='right' caption='[[4i73]], [[Resolution\|resolution]] 2.18Å' scene=''>		<StructureSection load='4i73' size='340' side='right' caption='[[4i73]], [[Resolution\|resolution]] 2.18Å' scene=''>
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	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">Tb927.3.2960 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=999953 TRYB2])</td></tr>		<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">Tb927.3.2960 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=999953 TRYB2])</td></tr>
	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Purine_nucleosidase Purine nucleosidase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.2.2.1 3.2.2.1] </span></td></tr>		<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Purine_nucleosidase Purine nucleosidase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.2.2.1 3.2.2.1] </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=4i73 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4i73 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4i73 RCSB], [http://www.ebi.ac.uk/pdbsum/4i73 PDBsum]</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=4i73 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4i73 OCA], [http://pdbe.org/4i73 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4i73 RCSB], [http://www.ebi.ac.uk/pdbsum/4i73 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4i73 ProSAT]</span></td></tr>
	</table>		</table>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
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	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>		From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
	</div>		</div>
		+	<div class="pdbe-citations 4i73" style="background-color:#fffaf0;"></div>
	== References ==		== References ==
	<references/>		<references/>

OCA at 18:16, 21 December 2014

OCA — Sun, 21 Dec 2014 18:16:09 GMT

←Older revision		Revision as of 18:16, 21 December 2014
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-	~~{{STRUCTURE_4i73\| PDB=4i73 \| SCENE= }}~~	+	==Crystal structure of the Trypanosoma brucei Inosine-Adenosine-Guanosine nucleoside hydrolase in complex with compound UAMC-00312==
-	===Crystal structure of the Trypanosoma brucei Inosine-Adenosine-Guanosine nucleoside hydrolase in complex with compound UAMC-00312===	+	<StructureSection load='4i73' size='340' side='right' caption='[[4i73]], [[Resolution\|resolution]] 2.18Å' scene=''>
-	~~{{ABSTRACT_PUBMED_23897478}}~~	+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[4i73]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Tryb2 Tryb2]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4I73 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4I73 FirstGlance]. <br>
		+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=MBY:(2R,3R,4S)-2-(HYDROXYMETHYL)-1-[(4-HYDROXYTHIENO[3,2-D]PYRIMIDIN-7-YL)METHYL]PYRROLIDINE-3,4-DIOL'>MBY</scene>, <scene name='pdbligand=NI:NICKEL+(II)+ION'>NI</scene></td></tr>
		+	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[3epw\|3epw]], [[3fz0\|3fz0]], [[4i70\|4i70]], [[4i71\|4i71]], [[4i72\|4i72]], [[4i74\|4i74]], [[4i75\|4i75]]</td></tr>
		+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">Tb927.3.2960 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=999953 TRYB2])</td></tr>
		+	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Purine_nucleosidase Purine nucleosidase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.2.2.1 3.2.2.1] </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=4i73 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4i73 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4i73 RCSB], [http://www.ebi.ac.uk/pdbsum/4i73 PDBsum]</span></td></tr>
		+	</table>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Sleeping sickness is a deadly disease that primarily affects sub-Saharan Africa and is caused by protozoan parasites of the Trypanosoma genus. Trypanosomes are purine auxotrophs and their uptake pathway has long been appreciated as an attractive target for drug design. Recently, one tight-binding competitive inhibitor of the trypanosomal purine-specific nucleoside hydrolase (IAGNH) showed remarkable trypanocidal activity in a murine model of infection. Here, the enzymatic characterization of T. brucei brucei IAGNH is presented, together with its high-resolution structures in the unliganded form and in complexes with different inhibitors, including the trypanocidal compound UAMC-00363. A description of the crucial contacts that account for the high-affinity inhibition of IAGNH by iminoribitol-based compounds is provided and the molecular mechanism underlying the conformational change necessary for enzymatic catalysis is identified. It is demonstrated for the first time that metalorganic complexes can compete for binding at the active site of nucleoside hydrolase enzymes, mimicking the positively charged transition state of the enzymatic reaction. Moreover, we show that divalent metal ions can act as noncompetitive IAGNH inhibitors, stabilizing a nonproductive conformation of the catalytic loop. These results open a path for rational improvement of the potency and the selectivity of existing compounds and suggest new scaffolds that may be used as blueprints for the design of novel antitrypanosomal compounds.

-	~~==About this Structure==~~	+	Structures of purine nucleosidase from Trypanosoma brucei bound to isozyme-specific trypanocidals and a novel metalorganic inhibitor.,Giannese F, Berg M, Van der Veken P, Castagna V, Tornaghi P, Augustyns K, Degano M Acta Crystallogr D Biol Crystallogr. 2013 Aug;69(Pt 8):1553-66. doi:, 10.1107/S0907444913010792. Epub 2013 Jul 20. PMID:23897478<ref>PMID:23897478</ref>
-	~~[[4i73]] is~~ a ~~4 chain structure with sequence from [http://en~~.~~wikipedia~~.~~org/wiki/Tryb2 Tryb2]~~. ~~Full crystallographic information is available from [http~~:/~~/oca~~.~~weizmann~~.~~ac.il~~/~~oca-bin/ocashort?id=4I73 OCA].~~	+

-	==~~Reference~~==	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	~~<ref group="xtra">PMID:023897478</ref>~~<references ~~group="xtra"~~/><~~references~~/>	+	</div>
		+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
	[[Category: Purine nucleosidase]]		[[Category: Purine nucleosidase]]
	[[Category: Tryb2]]		[[Category: Tryb2]]
-	[[Category: Degano, M.]]	+	[[Category: Degano, M]]
-	[[Category: Giannese, F.]]	+	[[Category: Giannese, F]]
	[[Category: Hydrolase-hydrolase inhibitor complex]]		[[Category: Hydrolase-hydrolase inhibitor complex]]
	[[Category: Nh fold]]		[[Category: Nh fold]]
	[[Category: Nucleoside hydrolase]]		[[Category: Nucleoside hydrolase]]

OCA at 08:27, 18 December 2013

OCA — Wed, 18 Dec 2013 08:27:54 GMT

←Older revision		Revision as of 08:27, 18 December 2013
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	{{STRUCTURE_4i73\| PDB=4i73 \| SCENE= }}		{{STRUCTURE_4i73\| PDB=4i73 \| SCENE= }}
	===Crystal structure of the Trypanosoma brucei Inosine-Adenosine-Guanosine nucleoside hydrolase in complex with compound UAMC-00312===		===Crystal structure of the Trypanosoma brucei Inosine-Adenosine-Guanosine nucleoside hydrolase in complex with compound UAMC-00312===
-	{{~~ABSTRACT_PUBMED_16630632~~}}	+	{{ABSTRACT_PUBMED_23897478}}

	==About this Structure==		==About this Structure==
-	[[4i73]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/~~Trypanosoma_brucei_brucei_strain_927/4_gutat10.1 Trypanosoma brucei brucei strain 927/4 gutat10.1~~]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4I73 OCA].	+	[[4i73]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Tryb2 Tryb2]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4I73 OCA].

	==Reference==		==Reference==
-	<ref group="xtra">PMID:~~016630632~~</ref><references group="xtra"/><references/>	+	<ref group="xtra">PMID:023897478</ref><references group="xtra"/><references/>
	[[Category: Purine nucleosidase]]		[[Category: Purine nucleosidase]]
-	[[Category: ~~Trypanosoma brucei brucei strain 927/4 gutat10 1~~]]	+	[[Category: Tryb2]]
	[[Category: Degano, M.]]		[[Category: Degano, M.]]
	[[Category: Giannese, F.]]		[[Category: Giannese, F.]]

OCA at 20:54, 7 August 2013

OCA — Wed, 07 Aug 2013 20:54:50 GMT

←Older revision		Revision as of 20:54, 7 August 2013
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-	~~'''Unreleased~~ structure~~'''~~	+	{{STRUCTURE_4i73\| PDB=4i73 \| SCENE= }}
		+	===Crystal structure of the Trypanosoma brucei Inosine-Adenosine-Guanosine nucleoside hydrolase in complex with compound UAMC-00312===
		+	{{ABSTRACT_PUBMED_16630632}}

-	~~The entry~~ 4i73 is ~~ON HOLD until Paper Publication~~	+	==About this Structure==
		+	[[4i73]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Trypanosoma_brucei_brucei_strain_927/4_gutat10.1 Trypanosoma brucei brucei strain 927/4 gutat10.1]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4I73 OCA].

-	~~Authors~~: ~~Giannese, F.,~~ Degano, M.	+	==Reference==
-		+	<ref group="xtra">PMID:016630632</ref><references group="xtra"/><references/>
-	~~Description~~: ~~Crystal structure of the Trypanosoma brucei Inosine~~-~~Adenosine-Guanosine nucleoside~~ hydrolase in complex ~~with compound UAMC-00312~~	+	[[Category: Purine nucleosidase]]
		+	[[Category: Trypanosoma brucei brucei strain 927/4 gutat10 1]]
		+	[[Category: Degano, M.]]
		+	[[Category: Giannese, F.]]
		+	[[Category: Hydrolase-hydrolase inhibitor complex]]
		+	[[Category: Nh fold]]
		+	[[Category: Nucleoside hydrolase]]

OCA at 07:02, 2 May 2013

OCA — Thu, 02 May 2013 07:02:04 GMT

←Older revision		Revision as of 07:02, 2 May 2013
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 4i73 is ON HOLD	+	The entry 4i73 is ON HOLD until Paper Publication

	Authors: Giannese, F., Degano, M.		Authors: Giannese, F., Degano, M.

	Description: Crystal structure of the Trypanosoma brucei Inosine-Adenosine-Guanosine nucleoside hydrolase in complex with compound UAMC-00312		Description: Crystal structure of the Trypanosoma brucei Inosine-Adenosine-Guanosine nucleoside hydrolase in complex with compound UAMC-00312

OCA: Protected "4i73" [edit=sysop:move=sysop]

OCA — Wed, 12 Dec 2012 20:49:03 GMT

Protected "4i73" [edit=sysop:move=sysop]

←Older revision

Revision as of 20:49, 12 December 2012

OCA: New page: '''Unreleased structure''' The entry 4i73 is ON HOLD Authors: Giannese, F., Degano, M. Description: Crystal structure of the Trypanosoma brucei Inosine-Adenosine-Guanosine nucleoside h...

OCA — Wed, 12 Dec 2012 20:49:02 GMT

New page: '''Unreleased structure''' The entry 4i73 is ON HOLD Authors: Giannese, F., Degano, M. Description: Crystal structure of the Trypanosoma brucei Inosine-Adenosine-Guanosine nucleoside h...

New page

'''Unreleased structure'''

The entry 4i73 is ON HOLD

Authors: Giannese, F., Degano, M.

Description: Crystal structure of the Trypanosoma brucei Inosine-Adenosine-Guanosine nucleoside hydrolase in complex with compound UAMC-00312