5wa8 - Revision history

OCA at 14:09, 4 October 2023

2023-10-04T14:09:31Z

←Older revision		Revision as of 14:09, 4 October 2023
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	==Human Histidine Triad Nucleotide Binding Protein 1 (hHint1) H112N mutant nucleoside L-Ala phosphoramidate substrate complex==		==Human Histidine Triad Nucleotide Binding Protein 1 (hHint1) H112N mutant nucleoside L-Ala phosphoramidate substrate complex==
-	<StructureSection load='5wa8' size='340' side='right' caption='[[5wa8]], [[Resolution\|resolution]] 1.30Å' scene=''>	+	<StructureSection load='5wa8' size='340' side='right'caption='[[5wa8]], [[Resolution\|resolution]] 1.30Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[5wa8]] is a 2 chain structure with sequence from [~~http~~://en.wikipedia.org/wiki/~~Human Human~~]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5WA8 OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=5WA8 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[5wa8]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5WA8 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5WA8 FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=9ZA:[(2~{R},3~{S},4~{R},5~{R})-5-(6-aminopurin-9-yl)-3,4-bis(oxidanyl)oxolan-2-yl]methoxy-~{N}-[(2~{S})-1-methoxy-1-oxidanylidene-propan-2-yl]phosphonamidic+acid'>9ZA</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</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]] 1.3Å</td></tr>
-	~~<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[5ipb\|5ipb]], [[5ipc\|5ipc]], [[5kma\|5kma]], [[5kmb\|5kmb]], [[3tw2\|3tw2]]</td></tr>~~	+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=9ZA:[(2~{R},3~{S},4~{R},5~{R})-5-(6-aminopurin-9-yl)-3,4-bis(oxidanyl)oxolan-2-yl]methoxy-~{N}-[(2~{S})-1-methoxy-1-oxidanylidene-propan-2-yl]phosphonamidic+acid'>9ZA</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene></td></tr>
-	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">HINT1, HINT, PKCI1, PRKCNH1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=5wa8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5wa8 OCA], [https://pdbe.org/5wa8 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5wa8 RCSB], [https://www.ebi.ac.uk/pdbsum/5wa8 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5wa8 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=5wa8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5wa8 OCA], [~~http~~://pdbe.org/5wa8 PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=5wa8 RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/5wa8 PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=5wa8 ProSAT]</span></td></tr>	+
	</table>		</table>
	== Function ==		== Function ==
-	[~~[http~~://www.uniprot.org/uniprot/HINT1_HUMAN HINT1_HUMAN]] Hydrolyzes adenosine 5'-monophosphoramidate substrates such as AMP-morpholidate, AMP-N-alanine methyl ester, AMP-alpha-acetyl lysine methyl ester and AMP-NH2 (By similarity).	+	[https://www.uniprot.org/uniprot/HINT1_HUMAN HINT1_HUMAN] Hydrolyzes adenosine 5'-monophosphoramidate substrates such as AMP-morpholidate, AMP-N-alanine methyl ester, AMP-alpha-acetyl lysine methyl ester and AMP-NH2 (By similarity).
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
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	</div>		</div>
	<div class="pdbe-citations 5wa8" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 5wa8" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Histidine triad nucleotide-binding protein 3D structures\|Histidine triad nucleotide-binding protein 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Human~~]]	+	[[Category: Homo sapiens]]
-	[[Category: ~~Finzel, B C~~]]	+	[[Category: Large Structures]]
-	[[Category: ~~Maize, K M~~]]	+	[[Category: Finzel BC]]
-	[[Category: ~~Histidine triad]]~~	+	[[Category: Maize KM]]
-	~~[[Category: Hydrolase~~]]	+

OCA at 10:32, 22 November 2017

2017-11-22T10:32:38Z

←Older revision		Revision as of 10:32, 22 November 2017
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	<StructureSection load='5wa8' size='340' side='right' caption='[[5wa8]], [[Resolution\|resolution]] 1.30Å' scene=''>		<StructureSection load='5wa8' size='340' side='right' caption='[[5wa8]], [[Resolution\|resolution]] 1.30Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[5wa8]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5WA8 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5WA8 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[5wa8]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5WA8 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5WA8 FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=9ZA:[(2~{R},3~{S},4~{R},5~{R})-5-(6-aminopurin-9-yl)-3,4-bis(oxidanyl)oxolan-2-yl]methoxy-~{N}-[(2~{S})-1-methoxy-1-oxidanylidene-propan-2-yl]phosphonamidic+acid'>9ZA</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=9ZA:[(2~{R},3~{S},4~{R},5~{R})-5-(6-aminopurin-9-yl)-3,4-bis(oxidanyl)oxolan-2-yl]methoxy-~{N}-[(2~{S})-1-methoxy-1-oxidanylidene-propan-2-yl]phosphonamidic+acid'>9ZA</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene></td></tr>
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[5ipb\|5ipb]], [[5ipc\|5ipc]], [[5kma\|5kma]], [[5kmb\|5kmb]], [[3tw2\|3tw2]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[5ipb\|5ipb]], [[5ipc\|5ipc]], [[5kma\|5kma]], [[5kmb\|5kmb]], [[3tw2\|3tw2]]</td></tr>
		+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">HINT1, HINT, PKCI1, PRKCNH1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=5wa8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5wa8 OCA], [http://pdbe.org/5wa8 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5wa8 RCSB], [http://www.ebi.ac.uk/pdbsum/5wa8 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5wa8 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=5wa8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5wa8 OCA], [http://pdbe.org/5wa8 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5wa8 RCSB], [http://www.ebi.ac.uk/pdbsum/5wa8 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5wa8 ProSAT]</span></td></tr>
	</table>		</table>
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	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Human]]
	[[Category: Finzel, B C]]		[[Category: Finzel, B C]]
	[[Category: Maize, K M]]		[[Category: Maize, K M]]
	[[Category: Histidine triad]]		[[Category: Histidine triad]]
	[[Category: Hydrolase]]		[[Category: Hydrolase]]

OCA at 06:52, 18 October 2017

2017-10-18T06:52:32Z

←Older revision		Revision as of 06:52, 18 October 2017
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 5wa8 is ~~ON HOLD until Paper~~ Publication	+	==Human Histidine Triad Nucleotide Binding Protein 1 (hHint1) H112N mutant nucleoside L-Ala phosphoramidate substrate complex==
		+	<StructureSection load='5wa8' size='340' side='right' caption='[[5wa8]], [[Resolution\|resolution]] 1.30Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[5wa8]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5WA8 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5WA8 FirstGlance]. <br>
		+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=9ZA:[(2~{R},3~{S},4~{R},5~{R})-5-(6-aminopurin-9-yl)-3,4-bis(oxidanyl)oxolan-2-yl]methoxy-~{N}-[(2~{S})-1-methoxy-1-oxidanylidene-propan-2-yl]phosphonamidic+acid'>9ZA</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene></td></tr>
		+	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[5ipb\|5ipb]], [[5ipc\|5ipc]], [[5kma\|5kma]], [[5kmb\|5kmb]], [[3tw2\|3tw2]]</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=5wa8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5wa8 OCA], [http://pdbe.org/5wa8 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5wa8 RCSB], [http://www.ebi.ac.uk/pdbsum/5wa8 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5wa8 ProSAT]</span></td></tr>
		+	</table>
		+	== Function ==
		+	[[http://www.uniprot.org/uniprot/HINT1_HUMAN HINT1_HUMAN]] Hydrolyzes adenosine 5'-monophosphoramidate substrates such as AMP-morpholidate, AMP-N-alanine methyl ester, AMP-alpha-acetyl lysine methyl ester and AMP-NH2 (By similarity).
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Nucleotide analogs that incorporate a metabolically labile nucleoside phosphoramidate (a ProTide) have found utility as prodrugs. In humans, ProTides can be cleaved by human histidine triad nucleotide binding protein 1 (hHint1) to expose the nucleotide monophosphate. Activation by this route circumvents highly selective nucleoside kinases that limit the use of nucleosides as prodrugs. To better understand the diversity of potential substrates of hHint1, we created and studied a series of phosphoramidate nucleosides. Using a combination of enzyme kinetics, X-ray crystallography, and isothermal titration calorimetry with both wild-type and inactive mutant enzymes, we have been able to explore the energetics of substrate binding and establish a structural basis for catalytic efficiency. Diverse nucleobases are well tolerated, but portions of the ribose are needed to position substrates for catalysis. Beneficial characteristics of the amine leaving group are also revealed. Structural principles revealed by these results may be exploited to tune the rate of substrate hydrolysis to strategically alter the intracellular release of the product nucleoside monophosphate from the ProTide.

-	~~Authors~~:	+	A Crystal Structure-Based Guide to the Design of Human Histidine Triad Nucleotide Binding Protein 1 (hHint1) Activated ProTides.,Maize KM, Shah R, Strom A, Kumarapperuma SC, Zhou AL, Wagner CR, Finzel BC Mol Pharm. 2017 Oct 2. doi: 10.1021/acs.molpharmaceut.7b00664. PMID:28968488<ref>PMID:28968488</ref>

-	~~Description~~:	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	[[Category: ~~Unreleased Structures~~]]	+	</div>
		+	<div class="pdbe-citations 5wa8" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Finzel, B C]]
		+	[[Category: Maize, K M]]
		+	[[Category: Histidine triad]]
		+	[[Category: Hydrolase]]

OCA: Protected "5wa8" [edit=sysop:move=sysop]

2017-09-27T14:37:03Z

Protected "5wa8" [edit=sysop:move=sysop]

←Older revision

Revision as of 14:37, 27 September 2017

OCA: New page: '''Unreleased structure''' The entry 5wa8 is ON HOLD until Paper Publication Authors: Description: Category: Unreleased Structures

2017-09-27T14:37:02Z

New page: '''Unreleased structure''' The entry 5wa8 is ON HOLD until Paper Publication Authors: Description: Category: Unreleased Structures

New page

'''Unreleased structure'''

The entry 5wa8 is ON HOLD until Paper Publication

Authors:

Description:
[[Category: Unreleased Structures]]