6txc - Revision history

OCA at 13:11, 24 January 2024

OCA — Wed, 24 Jan 2024 13:11:34 GMT

←Older revision		Revision as of 13:11, 24 January 2024
Line 3:		Line 3:
	<StructureSection load='6txc' size='340' side='right'caption='[[6txc]], [[Resolution\|resolution]] 2.84Å' scene=''>		<StructureSection load='6txc' size='340' side='right'caption='[[6txc]], [[Resolution\|resolution]] 2.84Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[6txc]] is a 16 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=6TXC OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://proteopedia.org/fgij/fg.htm?mol=6TXC FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6txc]] is a 16 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=6TXC OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6TXC FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=0KX:2-DEOXY-5-O-[(R)-HYDROXY{[(R)-HYDROXY(PHOSPHONOOXY)PHOSPHORYL]AMINO}PHOSPHORYL]CYTIDINE'>0KX</scene>, <scene name='pdbligand=DTP:2-DEOXYADENOSINE+5-TRIPHOSPHATE'>DTP</scene>, <scene name='pdbligand=FE:FE+(III)+ION'>FE</scene>, <scene name='pdbligand=GTP:GUANOSINE-5-TRIPHOSPHATE'>GTP</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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]] 2.84Å</td></tr>
-	~~<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[6tx0\|6tx0]], [[6txa\|6txa]]</td></tr>~~	+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=0KX:2-DEOXY-5-O-[(R)-HYDROXY{[(R)-HYDROXY(PHOSPHONOOXY)PHOSPHORYL]AMINO}PHOSPHORYL]CYTIDINE'>0KX</scene>, <scene name='pdbligand=DTP:2-DEOXYADENOSINE+5-TRIPHOSPHATE'>DTP</scene>, <scene name='pdbligand=FE:FE+(III)+ION'>FE</scene>, <scene name='pdbligand=GTP:GUANOSINE-5-TRIPHOSPHATE'>GTP</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
-	~~<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">SAMHD1, MOP5 ([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=6txc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6txc OCA], [https://pdbe.org/6txc PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6txc RCSB], [https://www.ebi.ac.uk/pdbsum/6txc PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6txc 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=6txc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6txc OCA], [~~http~~://pdbe.org/6txc PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=6txc RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/6txc PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=6txc ProSAT]</span></td></tr>	+
	</table>		</table>
	== Disease ==		== Disease ==
-	[~~[http~~://www.uniprot.org/uniprot/SAMH1_HUMAN SAMH1_HUMAN]] Defects in SAMHD1 are the cause of Aicardi-Goutieres syndrome type 5 (AGS5) [MIM:[~~http~~://omim.org/entry/612952 612952]]. A form of Aicardi-Goutieres syndrome, a genetically heterogeneous disease characterized by cerebral atrophy, leukoencephalopathy, intracranial calcifications, chronic cerebrospinal fluid (CSF) lymphocytosis, increased CSF alpha-interferon, and negative serologic investigations for common prenatal infection. Clinical features as thrombocytopenia, hepatosplenomegaly and elevated hepatic transaminases along with intermittent fever may erroneously suggest an infective process. Severe neurological dysfunctions manifest in infancy as progressive microcephaly, spasticity, dystonic posturing and profound psychomotor retardation. Death often occurs in early childhood.<ref>PMID:19525956</ref> <ref>PMID:20842748</ref> Defects in SAMHD1 are the cause of chilblain lupus type 2 (CHBL2) [MIM:[~~http~~://omim.org/entry/614415 614415]]. A rare cutaneous form of lupus erythematosus. Affected individuals present with painful bluish-red papular or nodular lesions of the skin in acral locations precipitated by cold and wet exposure at temperatures less than 10 degrees centigrade.<ref>PMID:21204240</ref>	+	[https://www.uniprot.org/uniprot/SAMH1_HUMAN SAMH1_HUMAN] Defects in SAMHD1 are the cause of Aicardi-Goutieres syndrome type 5 (AGS5) [MIM:[https://omim.org/entry/612952 612952]. A form of Aicardi-Goutieres syndrome, a genetically heterogeneous disease characterized by cerebral atrophy, leukoencephalopathy, intracranial calcifications, chronic cerebrospinal fluid (CSF) lymphocytosis, increased CSF alpha-interferon, and negative serologic investigations for common prenatal infection. Clinical features as thrombocytopenia, hepatosplenomegaly and elevated hepatic transaminases along with intermittent fever may erroneously suggest an infective process. Severe neurological dysfunctions manifest in infancy as progressive microcephaly, spasticity, dystonic posturing and profound psychomotor retardation. Death often occurs in early childhood.<ref>PMID:19525956</ref> <ref>PMID:20842748</ref> Defects in SAMHD1 are the cause of chilblain lupus type 2 (CHBL2) [MIM:[https://omim.org/entry/614415 614415]. A rare cutaneous form of lupus erythematosus. Affected individuals present with painful bluish-red papular or nodular lesions of the skin in acral locations precipitated by cold and wet exposure at temperatures less than 10 degrees centigrade.<ref>PMID:21204240</ref>
	== Function ==		== Function ==
-	[~~[http~~://www.uniprot.org/uniprot/SAMH1_HUMAN SAMH1_HUMAN]] Putative nuclease involved in innate immune response by acting as a negative regulator of the cell-intrinsic antiviral response. May play a role in mediating proinflammatory responses to TNF-alpha signaling.<ref>PMID:18546154</ref> <ref>PMID:19525956</ref>	+	[https://www.uniprot.org/uniprot/SAMH1_HUMAN SAMH1_HUMAN] Putative nuclease involved in innate immune response by acting as a negative regulator of the cell-intrinsic antiviral response. May play a role in mediating proinflammatory responses to TNF-alpha signaling.<ref>PMID:18546154</ref> <ref>PMID:19525956</ref>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
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	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Human~~]]	+	[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Arnold~~, L H~~]]	+	[[Category: Arnold LH]]
-	[[Category: Caswell~~, S J~~]]	+	[[Category: Caswell SJ]]
-	[[Category: Kelly, G]]	+	[[Category: Kelly G]]
-	[[Category: Kunzelmann, S]]	+	[[Category: Kunzelmann S]]
-	[[Category: Morris~~, E R~~]]	+	[[Category: Morris ER]]
-	[[Category: Purkiss, A]]	+	[[Category: Purkiss A]]
-	[[Category: Taylor~~, I A]]~~	+	[[Category: Taylor IA]]
-	~~[[Category: Binuclear]]~~	+
-	~~[[Category: Hd]]~~	+
-	~~[[Category: Hydrolase]]~~	+
-	~~[[Category: Metallo-enzyme]]~~	+
-	~~[[Category: Triphosphohydrolase~~]]	+

OCA at 14:36, 8 July 2020

OCA — Wed, 08 Jul 2020 14:36:36 GMT

←Older revision		Revision as of 14:36, 8 July 2020
Line 1:		Line 1:

	==Crystal structure of tetrameric human wt-SAMHD1 (residues 109-626) with GTP, dATP, dCMPNPP and Mg==		==Crystal structure of tetrameric human wt-SAMHD1 (residues 109-626) with GTP, dATP, dCMPNPP and Mg==
-	<StructureSection load='6txc' size='340' side='right'caption='[[6txc]]' scene=''>	+	<StructureSection load='6txc' size='340' side='right'caption='[[6txc]], [[Resolution\|resolution]] 2.84Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6TXC OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6TXC FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6txc]] is a 16 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=6TXC OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6TXC FirstGlance]. <br>
-	</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=6txc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6txc OCA], [http://pdbe.org/6txc PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6txc RCSB], [http://www.ebi.ac.uk/pdbsum/6txc PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6txc ProSAT]</span></td></tr>	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=0KX:2-DEOXY-5-O-[(R)-HYDROXY{[(R)-HYDROXY(PHOSPHONOOXY)PHOSPHORYL]AMINO}PHOSPHORYL]CYTIDINE'>0KX</scene>, <scene name='pdbligand=DTP:2-DEOXYADENOSINE+5-TRIPHOSPHATE'>DTP</scene>, <scene name='pdbligand=FE:FE+(III)+ION'>FE</scene>, <scene name='pdbligand=GTP:GUANOSINE-5-TRIPHOSPHATE'>GTP</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
		+	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[6tx0\|6tx0]], [[6txa\|6txa]]</td></tr>
		+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">SAMHD1, MOP5 ([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://proteopedia.org/fgij/fg.htm?mol=6txc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6txc OCA], [http://pdbe.org/6txc PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6txc RCSB], [http://www.ebi.ac.uk/pdbsum/6txc PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6txc ProSAT]</span></td></tr>
	</table>		</table>
		+	== Disease ==
		+	[[http://www.uniprot.org/uniprot/SAMH1_HUMAN SAMH1_HUMAN]] Defects in SAMHD1 are the cause of Aicardi-Goutieres syndrome type 5 (AGS5) [MIM:[http://omim.org/entry/612952 612952]]. A form of Aicardi-Goutieres syndrome, a genetically heterogeneous disease characterized by cerebral atrophy, leukoencephalopathy, intracranial calcifications, chronic cerebrospinal fluid (CSF) lymphocytosis, increased CSF alpha-interferon, and negative serologic investigations for common prenatal infection. Clinical features as thrombocytopenia, hepatosplenomegaly and elevated hepatic transaminases along with intermittent fever may erroneously suggest an infective process. Severe neurological dysfunctions manifest in infancy as progressive microcephaly, spasticity, dystonic posturing and profound psychomotor retardation. Death often occurs in early childhood.<ref>PMID:19525956</ref> <ref>PMID:20842748</ref> Defects in SAMHD1 are the cause of chilblain lupus type 2 (CHBL2) [MIM:[http://omim.org/entry/614415 614415]]. A rare cutaneous form of lupus erythematosus. Affected individuals present with painful bluish-red papular or nodular lesions of the skin in acral locations precipitated by cold and wet exposure at temperatures less than 10 degrees centigrade.<ref>PMID:21204240</ref>
		+	== Function ==
		+	[[http://www.uniprot.org/uniprot/SAMH1_HUMAN SAMH1_HUMAN]] Putative nuclease involved in innate immune response by acting as a negative regulator of the cell-intrinsic antiviral response. May play a role in mediating proinflammatory responses to TNF-alpha signaling.<ref>PMID:18546154</ref> <ref>PMID:19525956</ref>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	SAMHD1 regulates cellular 2'-deoxynucleoside-5'-triphosphate (dNTP) homeostasis by catalysing the hydrolysis of dNTPs into 2'-deoxynucleosides and triphosphate. In CD4(+) myeloid lineage and resting T-cells, SAMHD1 blocks HIV-1 and other viral infections by depletion of the dNTP pool to a level that cannot support replication. SAMHD1 mutations are associated with the autoimmune disease Aicardi-Goutieres syndrome and hypermutated cancers. Furthermore, SAMHD1 sensitises cancer cells to nucleoside-analogue anti-cancer therapies and is linked with DNA repair and suppression of the interferon response to cytosolic nucleic acids. Nevertheless, despite its requirement in these processes, the fundamental mechanism of SAMHD1-catalysed dNTP hydrolysis remained unknown. Here, we present structural and enzymological data showing that SAMHD1 utilises an active site, bi-metallic iron-magnesium centre that positions a hydroxide nucleophile in-line with the P(alpha)-O(5') bond to catalyse phosphoester bond hydrolysis. This precise molecular mechanism for SAMHD1 catalysis, reveals how SAMHD1 down-regulates cellular dNTP and modulates the efficacy of nucleoside-based anti-cancer and anti-viral therapies.
		+
		+	Crystal structures of SAMHD1 inhibitor complexes reveal the mechanism of water-mediated dNTP hydrolysis.,Morris ER, Caswell SJ, Kunzelmann S, Arnold LH, Purkiss AG, Kelly G, Taylor IA Nat Commun. 2020 Jun 23;11(1):3165. doi: 10.1038/s41467-020-16983-2. PMID:32576829<ref>PMID:32576829</ref>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	<div class="pdbe-citations 6txc" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Human]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Arnold LH]]	+	[[Category: Arnold, L H]]
-	[[Category: Caswell SJ]]	+	[[Category: Caswell, S J]]
-	[[Category: Kelly G]]	+	[[Category: Kelly, G]]
-	[[Category: Kunzelmann S]]	+	[[Category: Kunzelmann, S]]
-	[[Category: Morris ER]]	+	[[Category: Morris, E R]]
-	[[Category: Purkiss A]]	+	[[Category: Purkiss, A]]
-	[[Category: Taylor IA]]	+	[[Category: Taylor, I A]]
		+	[[Category: Binuclear]]
		+	[[Category: Hd]]
		+	[[Category: Hydrolase]]
		+	[[Category: Metallo-enzyme]]
		+	[[Category: Triphosphohydrolase]]

OCA at 06:23, 25 June 2020

OCA — Thu, 25 Jun 2020 06:23:44 GMT

←Older revision		Revision as of 06:23, 25 June 2020
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 6txc is ~~ON HOLD~~	+	==Crystal structure of tetrameric human wt-SAMHD1 (residues 109-626) with GTP, dATP, dCMPNPP and Mg==
-		+	<StructureSection load='6txc' size='340' side='right'caption='[[6txc]]' scene=''>
-	~~Authors~~:	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6TXC OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6TXC FirstGlance]. <br>
-	~~Description~~:	+	</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=6txc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6txc OCA], [http://pdbe.org/6txc PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6txc RCSB], [http://www.ebi.ac.uk/pdbsum/6txc PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6txc ProSAT]</span></td></tr>
-	[[Category: ~~Unreleased Structures~~]]	+	</table>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Large Structures]]
		+	[[Category: Arnold LH]]
		+	[[Category: Caswell SJ]]
		+	[[Category: Kelly G]]
		+	[[Category: Kunzelmann S]]
		+	[[Category: Morris ER]]
		+	[[Category: Purkiss A]]
		+	[[Category: Taylor IA]]

OCA: Protected "6txc" [edit=sysop:move=sysop]

OCA — Wed, 22 Jan 2020 14:05:07 GMT

Protected "6txc" [edit=sysop:move=sysop]

←Older revision

Revision as of 14:05, 22 January 2020

OCA: New page: '''Unreleased structure''' The entry 6txc is ON HOLD Authors: Description: Category: Unreleased Structures

OCA — Wed, 22 Jan 2020 14:05:04 GMT

New page: '''Unreleased structure''' The entry 6txc is ON HOLD Authors: Description: Category: Unreleased Structures

New page

'''Unreleased structure'''

The entry 6txc is ON HOLD

Authors:

Description:
[[Category: Unreleased Structures]]