5z1h - Revision history

OCA at 10:26, 27 March 2024

OCA — Wed, 27 Mar 2024 10:26:17 GMT

←Older revision		Revision as of 10:26, 27 March 2024
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	<StructureSection load='5z1h' size='340' side='right'caption='[[5z1h]], [[Resolution\|resolution]] 2.40Å' scene=''>		<StructureSection load='5z1h' size='340' side='right'caption='[[5z1h]], [[Resolution\|resolution]] 2.40Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[5z1h]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5Z1H OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://proteopedia.org/fgij/fg.htm?mol=5Z1H FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[5z1h]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Synthetic_construct Synthetic construct]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5Z1H OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5Z1H FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=FSJ:(1S,2S,3R,4S,6R)-4,6-diamino-3-{[(2S,3R)-3-amino-6-(fluoromethyl)-3,4-dihydro-2H-pyran-2-yl]oxy}-2-hydroxycyclohexyl+3-deoxy-4-C-methyl-3-(methylamino)-beta-L-arabinopyranoside'>FSJ</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]] 2.4Å</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=5z1h FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5z1h OCA], [~~http~~://pdbe.org/5z1h PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=5z1h RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/5z1h PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=5z1h ProSAT]</span></td></tr>	+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=FSJ:(1S,2S,3R,4S,6R)-4,6-diamino-3-{[(2S,3R)-3-amino-6-(fluoromethyl)-3,4-dihydro-2H-pyran-2-yl]oxy}-2-hydroxycyclohexyl+3-deoxy-4-C-methyl-3-(methylamino)-beta-L-arabinopyranoside'>FSJ</scene></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=5z1h FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5z1h OCA], [https://pdbe.org/5z1h PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5z1h RCSB], [https://www.ebi.ac.uk/pdbsum/5z1h PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5z1h ProSAT]</span></td></tr>
	</table>		</table>
-	<div style="background-color:#fffaf0;">
-	== Publication Abstract from PubMed ==
-	Aminoglycosides (AG) are antibiotics that lower the accuracy of protein synthesis by targeting a highly-conserved RNA helix of the ribosomal A-site. The discovery of AGs that selectively target the eukaryotic ribosome, but lack activity in prokaryotes, are promising as antiprotozoals for the treatment of neglected tropical diseases, and as therapies to read-through point-mutation genetic diseases. However, a single nucleobase change A1408G in the eukaryotic A-site leads to negligible affinity for most AGs. Herein we report the synthesis of 6'-fluoro sisomicin, the first 6'-fluorinated aminoglycoside, which specifically interacts with the protozoal cytoplasmic rRNA A-site, but not the bacterial A-site, as evidenced by X-ray co-crystal structures. The respective dispositions of 6'-F sisomicin within the bacterial and protozoal A-sites reveal that fluorine acts only as an H-bond acceptor to favorably interact with G1408 of the protozoal A-site. Unlike aminoglycosides containing a 6'-amino group, 6'-F sisomicin cannot participate in the H-bonding pattern that characterizes stable pseudo base-pairs with A1408 of the bacterial A-sites. Based on these structural observations it may be possible to shift the biological activity of aminoglycosides to act preferentially as antiprotozoals. These findings expand the repertoire of small-molecules targeting the eukaryotic ribosome and demonstrate the usefulness of fluorine as a design element.
-
-	Structure-Based Design of a Eukaryote-Selective Antiprotozoal Fluorinated Aminoglycoside.,Kanazawa H, Saavedra OM, Maianti JP, Young SA, Izquierdo L, Smith TK, Hanessian S, Kondo J ChemMedChem. 2018 May 15. doi: 10.1002/cmdc.201800166. PMID:29766661<ref>PMID:29766661</ref>
-
-	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	</div>
-	<div class="pdbe-citations 5z1h" style="background-color:#fffaf0;"></div>
-	== References ==
-	<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: ~~Hanessian, S~~]]	+	[[Category: Synthetic construct]]
-	[[Category: ~~Kanazawa, H~~]]	+	[[Category: Hanessian S]]
-	[[Category: ~~Kondo, J~~]]	+	[[Category: Kanazawa H]]
-	[[Category: ~~Aminoglycoside]]~~	+	[[Category: Kondo J]]
-	~~[[Category: Rna]]~~	+
-	~~[[Category: Rrna~~]]	+

OCA at 21:12, 28 October 2020

OCA — Wed, 28 Oct 2020 21:12:59 GMT

←Older revision		Revision as of 21:12, 28 October 2020
Line 1:		Line 1:

	==Crystal structure of the bacterial ribosomal decoding site in complex with 6'-fluoro sisomicin==		==Crystal structure of the bacterial ribosomal decoding site in complex with 6'-fluoro sisomicin==
-	<StructureSection load='5z1h' size='340' side='right' caption='[[5z1h]], [[Resolution\|resolution]] 2.40Å' scene=''>	+	<StructureSection load='5z1h' size='340' side='right'caption='[[5z1h]], [[Resolution\|resolution]] 2.40Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[5z1h]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5Z1H OCA]. For a <b>guided tour on the structure components</b> use [http://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=5Z1H FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[5z1h]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5Z1H OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=5Z1H FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=FSJ:(1S,2S,3R,4S,6R)-4,6-diamino-3-{[(2S,3R)-3-amino-6-(fluoromethyl)-3,4-dihydro-2H-pyran-2-yl]oxy}-2-hydroxycyclohexyl+3-deoxy-4-C-methyl-3-(methylamino)-beta-L-arabinopyranoside'>FSJ</scene></td></tr>	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=FSJ:(1S,2S,3R,4S,6R)-4,6-diamino-3-{[(2S,3R)-3-amino-6-(fluoromethyl)-3,4-dihydro-2H-pyran-2-yl]oxy}-2-hydroxycyclohexyl+3-deoxy-4-C-methyl-3-(methylamino)-beta-L-arabinopyranoside'>FSJ</scene></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=5z1h FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5z1h OCA], [http://pdbe.org/5z1h PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5z1h RCSB], [http://www.ebi.ac.uk/pdbsum/5z1h PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5z1h 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=5z1h FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5z1h OCA], [http://pdbe.org/5z1h PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5z1h RCSB], [http://www.ebi.ac.uk/pdbsum/5z1h PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5z1h ProSAT]</span></td></tr>
	</table>		</table>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
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	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Large Structures]]
	[[Category: Hanessian, S]]		[[Category: Hanessian, S]]
	[[Category: Kanazawa, H]]		[[Category: Kanazawa, H]]

OCA at 05:29, 30 May 2018

OCA — Wed, 30 May 2018 05:29:33 GMT

←Older revision		Revision as of 05:29, 30 May 2018
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 5z1h is ~~ON HOLD until Paper~~ Publication	+	==Crystal structure of the bacterial ribosomal decoding site in complex with 6'-fluoro sisomicin==
		+	<StructureSection load='5z1h' size='340' side='right' caption='[[5z1h]], [[Resolution\|resolution]] 2.40Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[5z1h]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5Z1H OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5Z1H FirstGlance]. <br>
		+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=FSJ:(1S,2S,3R,4S,6R)-4,6-diamino-3-{[(2S,3R)-3-amino-6-(fluoromethyl)-3,4-dihydro-2H-pyran-2-yl]oxy}-2-hydroxycyclohexyl+3-deoxy-4-C-methyl-3-(methylamino)-beta-L-arabinopyranoside'>FSJ</scene></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=5z1h FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5z1h OCA], [http://pdbe.org/5z1h PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5z1h RCSB], [http://www.ebi.ac.uk/pdbsum/5z1h PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5z1h ProSAT]</span></td></tr>
		+	</table>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Aminoglycosides (AG) are antibiotics that lower the accuracy of protein synthesis by targeting a highly-conserved RNA helix of the ribosomal A-site. The discovery of AGs that selectively target the eukaryotic ribosome, but lack activity in prokaryotes, are promising as antiprotozoals for the treatment of neglected tropical diseases, and as therapies to read-through point-mutation genetic diseases. However, a single nucleobase change A1408G in the eukaryotic A-site leads to negligible affinity for most AGs. Herein we report the synthesis of 6'-fluoro sisomicin, the first 6'-fluorinated aminoglycoside, which specifically interacts with the protozoal cytoplasmic rRNA A-site, but not the bacterial A-site, as evidenced by X-ray co-crystal structures. The respective dispositions of 6'-F sisomicin within the bacterial and protozoal A-sites reveal that fluorine acts only as an H-bond acceptor to favorably interact with G1408 of the protozoal A-site. Unlike aminoglycosides containing a 6'-amino group, 6'-F sisomicin cannot participate in the H-bonding pattern that characterizes stable pseudo base-pairs with A1408 of the bacterial A-sites. Based on these structural observations it may be possible to shift the biological activity of aminoglycosides to act preferentially as antiprotozoals. These findings expand the repertoire of small-molecules targeting the eukaryotic ribosome and demonstrate the usefulness of fluorine as a design element.

-	~~Authors: Kanazawa~~, H., ~~Hanessian~~, S., Kondo, J.	+	Structure-Based Design of a Eukaryote-Selective Antiprotozoal Fluorinated Aminoglycoside.,Kanazawa H, Saavedra OM, Maianti JP, Young SA, Izquierdo L, Smith TK, Hanessian S, Kondo J ChemMedChem. 2018 May 15. doi: 10.1002/cmdc.201800166. PMID:29766661<ref>PMID:29766661</ref>

-	~~Description: Crystal structure~~ of the ~~bacterial ribosomal decoding site in complex with 6'-fluoro sisomicin~~	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	~~[[Category: Unreleased Structures]]~~	+	</div>
-	~~[[Category~~: ~~Kondo, J]]~~	+	<div class="pdbe-citations 5z1h" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
	[[Category: Hanessian, S]]		[[Category: Hanessian, S]]
	[[Category: Kanazawa, H]]		[[Category: Kanazawa, H]]
		+	[[Category: Kondo, J]]
		+	[[Category: Aminoglycoside]]
		+	[[Category: Rna]]
		+	[[Category: Rrna]]

OCA at 04:37, 31 January 2018

OCA — Wed, 31 Jan 2018 04:37:53 GMT

←Older revision		Revision as of 04:37, 31 January 2018
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 5z1h is ON HOLD	+	The entry 5z1h is ON HOLD until Paper Publication

	Authors: Kanazawa, H., Hanessian, S., Kondo, J.		Authors: Kanazawa, H., Hanessian, S., Kondo, J.

OCA: Protected "5z1h" [edit=sysop:move=sysop]

OCA — Wed, 03 Jan 2018 04:52:03 GMT

Protected "5z1h" [edit=sysop:move=sysop]

←Older revision

Revision as of 04:52, 3 January 2018

OCA: New page: '''Unreleased structure''' The entry 5z1h is ON HOLD Authors: Kanazawa, H., Hanessian, S., Kondo, J. Description: Crystal structure of the bacterial ribosomal decoding site in complex ...

OCA — Wed, 03 Jan 2018 04:52:02 GMT

New page: '''Unreleased structure''' The entry 5z1h is ON HOLD Authors: Kanazawa, H., Hanessian, S., Kondo, J. Description: Crystal structure of the bacterial ribosomal decoding site in complex ...

New page

'''Unreleased structure'''

The entry 5z1h is ON HOLD

Authors: Kanazawa, H., Hanessian, S., Kondo, J.

Description: Crystal structure of the bacterial ribosomal decoding site in complex with 6'-fluoro sisomicin
[[Category: Unreleased Structures]]
[[Category: Kondo, J]]
[[Category: Hanessian, S]]
[[Category: Kanazawa, H]]