5zo8 - Revision history

OCA at 10:28, 27 March 2024

OCA — Wed, 27 Mar 2024 10:28:43 GMT

←Older revision		Revision as of 10:28, 27 March 2024
Line 3:		Line 3:
	<StructureSection load='5zo8' size='340' side='right'caption='[[5zo8]], [[Resolution\|resolution]] 2.20Å' scene=''>		<StructureSection load='5zo8' size='340' side='right'caption='[[5zo8]], [[Resolution\|resolution]] 2.20Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[5zo8]] 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=5ZO8 OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://proteopedia.org/fgij/fg.htm?mol=5ZO8 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[5zo8]] 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=5ZO8 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5ZO8 FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=4C5:(2R)-2-azanyl-3-[(4-methoxyphenyl)-diphenyl-methyl]sulfanyl-propanoic+acid'>4C5</scene>, <scene name='pdbligand=ADP:ADENOSINE-5-DIPHOSPHATE'>ADP</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</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]] 2.2Å</td></tr>
-	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">KIF11, EG5, KNSL1, TRIP5 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>	+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=4C5:(2R)-2-azanyl-3-[(4-methoxyphenyl)-diphenyl-methyl]sulfanyl-propanoic+acid'>4C5</scene>, <scene name='pdbligand=ADP:ADENOSINE-5-DIPHOSPHATE'>ADP</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></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=5zo8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5zo8 OCA], [~~http~~://pdbe.org/5zo8 PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=5zo8 RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/5zo8 PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=5zo8 ProSAT]</span></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=5zo8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5zo8 OCA], [https://pdbe.org/5zo8 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5zo8 RCSB], [https://www.ebi.ac.uk/pdbsum/5zo8 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5zo8 ProSAT]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
-	[~~[http~~://www.uniprot.org/uniprot/KIF11_HUMAN KIF11_HUMAN]] Defects in KIF11 are the cause of microcephaly with or without chorioretinopathy, lymphedema, or mental retardation (MCLMR) [MIM:[~~http~~://omim.org/entry/152950 152950]]. An autosomal dominant disorder that involves an overlapping but variable spectrum of central nervous system and ocular developmental anomalies. Microcephaly ranges from mild to severe and is often associated with mild to moderate developmental delay and a characteristic facial phenotype with upslanting palpebral fissures, broad nose with rounded tip, long philtrum with thin upper lip, prominent chin, and prominent ears. Chorioretinopathy is the most common eye abnormality, but retinal folds, microphthalmia, and myopic and hypermetropic astigmatism have also been reported, and some individuals have no overt ocular phenotype. Congenital lymphedema, when present, is typically confined to the dorsa of the feet, and lymphoscintigraphy reveals the absence of radioactive isotope uptake from the webspaces between the toes.<ref>PMID:22284827</ref>	+	[https://www.uniprot.org/uniprot/KIF11_HUMAN KIF11_HUMAN] Defects in KIF11 are the cause of microcephaly with or without chorioretinopathy, lymphedema, or mental retardation (MCLMR) [MIM:[https://omim.org/entry/152950 152950]. An autosomal dominant disorder that involves an overlapping but variable spectrum of central nervous system and ocular developmental anomalies. Microcephaly ranges from mild to severe and is often associated with mild to moderate developmental delay and a characteristic facial phenotype with upslanting palpebral fissures, broad nose with rounded tip, long philtrum with thin upper lip, prominent chin, and prominent ears. Chorioretinopathy is the most common eye abnormality, but retinal folds, microphthalmia, and myopic and hypermetropic astigmatism have also been reported, and some individuals have no overt ocular phenotype. Congenital lymphedema, when present, is typically confined to the dorsa of the feet, and lymphoscintigraphy reveals the absence of radioactive isotope uptake from the webspaces between the toes.<ref>PMID:22284827</ref>
	== Function ==		== Function ==
-	[~~[http~~://www.uniprot.org/uniprot/KIF11_HUMAN KIF11_HUMAN]] Motor protein required for establishing a bipolar spindle. Blocking of KIF11 prevents centrosome migration and arrest cells in mitosis with monoastral microtubule arrays.<ref>PMID:19001501</ref>	+	[https://www.uniprot.org/uniprot/KIF11_HUMAN KIF11_HUMAN] Motor protein required for establishing a bipolar spindle. Blocking of KIF11 prevents centrosome migration and arrest cells in mitosis with monoastral microtubule arrays.<ref>PMID:19001501</ref>
-	~~<div style="background-color:#fffaf0;">~~	+
-	~~== Publication Abstract from PubMed ==~~	+
-	For a better understanding of protein-inhibitor interactions, we report structural, thermodynamic, and biological analyses of the interactions between S-trityl-l-cysteine (STLC) derivatives and the motor domain of kinesin spindle protein Eg5. Binding of STLC-type inhibitors to Eg5 was enthalpically driven and entropically unfavorable. The introduction of a para-methoxy substituent in one phenyl ring of STLC enhances its inhibitory activity resulting from a larger enthalpy gain possibly due to the increased shape complementarity. The substituent fits to a recess in the binding pocket. To avoid steric hindrance, the substituted STLC is nudged toward the side opposite to the recess, which enhances the interaction of Eg5 with the remaining part of the inhibitor. Further introduction of an ethylene linkage between two phenyl rings enhances Eg5 inhibitory activity by reducing the loss of entropy in forming the complex. This study provides valuable examples of enhancing protein-inhibitor interactions without forming additional hydrogen bonds.	+
-		+
-	Structural and Thermodynamic Basis of the Enhanced Interaction between Kinesin Spindle Protein Eg5 and STLC-type Inhibitors.,Yokoyama H, Sawada JI, Sato K, Ogo N, Kamei N, Ishikawa Y, Hara K, Asai A, Hashimoto H ACS Omega. 2018 Sep 28;3(9):12284-12294. doi: 10.1021/acsomega.8b00778., eCollection 2018 Sep 30. PMID:31459302<ref>PMID:31459302</ref>	+
-		+
-	~~From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>~~	+
-	~~</div>~~	+
-	~~<div class="pdbe-citations 5zo8" style="background-color:#fffaf0;"></div~~>	+
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Human~~]]	+	[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Sato, K]]	+	[[Category: Sato K]]
-	[[Category: Yokoyama, H]]	+	[[Category: Yokoyama H]]
-	~~[[Category: Cell cycle]]~~	+
-	~~[[Category: Motor domain atp binding~~]]	+

OCA at 21:22, 28 October 2020

OCA — Wed, 28 Oct 2020 21:22:12 GMT

←Older revision		Revision as of 21:22, 28 October 2020
Line 1:		Line 1:

	==Eg5 motor domain in complex with STLC-type inhibitor PVEI0021 (P21 type)==		==Eg5 motor domain in complex with STLC-type inhibitor PVEI0021 (P21 type)==
-	<StructureSection load='5zo8' size='340' side='right' caption='[[5zo8]], [[Resolution\|resolution]] 2.20Å' scene=''>	+	<StructureSection load='5zo8' size='340' side='right'caption='[[5zo8]], [[Resolution\|resolution]] 2.20Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[5zo8]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5ZO8 OCA]. For a <b>guided tour on the structure components</b> use [http://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=5ZO8 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[5zo8]] 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=5ZO8 OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=5ZO8 FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=4C5:(2R)-2-azanyl-3-[(4-methoxyphenyl)-diphenyl-methyl]sulfanyl-propanoic+acid'>4C5</scene>, <scene name='pdbligand=ADP:ADENOSINE-5-DIPHOSPHATE'>ADP</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=4C5:(2R)-2-azanyl-3-[(4-methoxyphenyl)-diphenyl-methyl]sulfanyl-propanoic+acid'>4C5</scene>, <scene name='pdbligand=ADP:ADENOSINE-5-DIPHOSPHATE'>ADP</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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=5zo8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5zo8 OCA], [http://pdbe.org/5zo8 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5zo8 RCSB], [http://www.ebi.ac.uk/pdbsum/5zo8 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5zo8 ProSAT]</span></td></tr>	+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">KIF11, EG5, KNSL1, TRIP5 ([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=5zo8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5zo8 OCA], [http://pdbe.org/5zo8 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5zo8 RCSB], [http://www.ebi.ac.uk/pdbsum/5zo8 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5zo8 ProSAT]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
Line 11:		Line 12:
	== Function ==		== Function ==
	[[http://www.uniprot.org/uniprot/KIF11_HUMAN KIF11_HUMAN]] Motor protein required for establishing a bipolar spindle. Blocking of KIF11 prevents centrosome migration and arrest cells in mitosis with monoastral microtubule arrays.<ref>PMID:19001501</ref>		[[http://www.uniprot.org/uniprot/KIF11_HUMAN KIF11_HUMAN]] Motor protein required for establishing a bipolar spindle. Blocking of KIF11 prevents centrosome migration and arrest cells in mitosis with monoastral microtubule arrays.<ref>PMID:19001501</ref>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	For a better understanding of protein-inhibitor interactions, we report structural, thermodynamic, and biological analyses of the interactions between S-trityl-l-cysteine (STLC) derivatives and the motor domain of kinesin spindle protein Eg5. Binding of STLC-type inhibitors to Eg5 was enthalpically driven and entropically unfavorable. The introduction of a para-methoxy substituent in one phenyl ring of STLC enhances its inhibitory activity resulting from a larger enthalpy gain possibly due to the increased shape complementarity. The substituent fits to a recess in the binding pocket. To avoid steric hindrance, the substituted STLC is nudged toward the side opposite to the recess, which enhances the interaction of Eg5 with the remaining part of the inhibitor. Further introduction of an ethylene linkage between two phenyl rings enhances Eg5 inhibitory activity by reducing the loss of entropy in forming the complex. This study provides valuable examples of enhancing protein-inhibitor interactions without forming additional hydrogen bonds.
		+
		+	Structural and Thermodynamic Basis of the Enhanced Interaction between Kinesin Spindle Protein Eg5 and STLC-type Inhibitors.,Yokoyama H, Sawada JI, Sato K, Ogo N, Kamei N, Ishikawa Y, Hara K, Asai A, Hashimoto H ACS Omega. 2018 Sep 28;3(9):12284-12294. doi: 10.1021/acsomega.8b00778., eCollection 2018 Sep 30. PMID:31459302<ref>PMID:31459302</ref>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	<div class="pdbe-citations 5zo8" style="background-color:#fffaf0;"></div>
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Human]]
		+	[[Category: Large Structures]]
	[[Category: Sato, K]]		[[Category: Sato, K]]
	[[Category: Yokoyama, H]]		[[Category: Yokoyama, H]]
	[[Category: Cell cycle]]		[[Category: Cell cycle]]
	[[Category: Motor domain atp binding]]		[[Category: Motor domain atp binding]]

OCA at 08:00, 10 October 2018

OCA — Wed, 10 Oct 2018 08:00:48 GMT

←Older revision		Revision as of 08:00, 10 October 2018
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 5zo8 is ~~ON HOLD until Paper Publication~~	+	==Eg5 motor domain in complex with STLC-type inhibitor PVEI0021 (P21 type)==
-		+	<StructureSection load='5zo8' size='340' side='right' caption='[[5zo8]], [[Resolution\|resolution]] 2.20Å' scene=''>
-	~~Authors~~: ~~Yokoyama~~, H., ~~Sato~~, K.	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>[[5zo8]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5ZO8 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5ZO8 FirstGlance]. <br>
-	~~Description~~: ~~Eg5 motor domain~~ in ~~complex~~ with ~~STLC-type inhibitor PVEI0021~~ (~~P21 type~~)	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=4C5:(2R)-2-azanyl-3-[(4-methoxyphenyl)-diphenyl-methyl]sulfanyl-propanoic+acid'>4C5</scene>, <scene name='pdbligand=ADP:ADENOSINE-5-DIPHOSPHATE'>ADP</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
-	[[Category: ~~Unreleased Structures~~]]	+	<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=5zo8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5zo8 OCA], [http://pdbe.org/5zo8 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5zo8 RCSB], [http://www.ebi.ac.uk/pdbsum/5zo8 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5zo8 ProSAT]</span></td></tr>
		+	</table>
		+	== Disease ==
		+	[[http://www.uniprot.org/uniprot/KIF11_HUMAN KIF11_HUMAN]] Defects in KIF11 are the cause of microcephaly with or without chorioretinopathy, lymphedema, or mental retardation (MCLMR) [MIM:[http://omim.org/entry/152950 152950]]. An autosomal dominant disorder that involves an overlapping but variable spectrum of central nervous system and ocular developmental anomalies. Microcephaly ranges from mild to severe and is often associated with mild to moderate developmental delay and a characteristic facial phenotype with upslanting palpebral fissures, broad nose with rounded tip, long philtrum with thin upper lip, prominent chin, and prominent ears. Chorioretinopathy is the most common eye abnormality, but retinal folds, microphthalmia, and myopic and hypermetropic astigmatism have also been reported, and some individuals have no overt ocular phenotype. Congenital lymphedema, when present, is typically confined to the dorsa of the feet, and lymphoscintigraphy reveals the absence of radioactive isotope uptake from the webspaces between the toes.<ref>PMID:22284827</ref>
		+	== Function ==
		+	[[http://www.uniprot.org/uniprot/KIF11_HUMAN KIF11_HUMAN]] Motor protein required for establishing a bipolar spindle. Blocking of KIF11 prevents centrosome migration and arrest cells in mitosis with monoastral microtubule arrays.<ref>PMID:19001501</ref>
		+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Sato, K]]
	[[Category: Yokoyama, H]]		[[Category: Yokoyama, H]]
-	[[Category: ~~Sato, K~~]]	+	[[Category: Cell cycle]]
		+	[[Category: Motor domain atp binding]]

OCA at 03:52, 11 July 2018

OCA — Wed, 11 Jul 2018 03:52:21 GMT

←Older revision		Revision as of 03:52, 11 July 2018
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 5zo8 is ON HOLD	+	The entry 5zo8 is ON HOLD until Paper Publication

	Authors: Yokoyama, H., Sato, K.		Authors: Yokoyama, H., Sato, K.

OCA at 05:29, 4 July 2018

OCA — Wed, 04 Jul 2018 05:29:23 GMT

←Older revision		Revision as of 05:29, 4 July 2018
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 5zo8 is ON HOLD ~~until Paper Publication~~	+	The entry 5zo8 is ON HOLD

	Authors: Yokoyama, H., Sato, K.		Authors: Yokoyama, H., Sato, K.

OCA at 06:32, 2 May 2018

OCA — Wed, 02 May 2018 06:32:41 GMT

←Older revision		Revision as of 06:32, 2 May 2018
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 5zo8 is ON HOLD	+	The entry 5zo8 is ON HOLD until Paper Publication

	Authors: Yokoyama, H., Sato, K.		Authors: Yokoyama, H., Sato, K.

OCA: Protected "5zo8" [edit=sysop:move=sysop]

OCA — Wed, 18 Apr 2018 04:07:26 GMT

Protected "5zo8" [edit=sysop:move=sysop]

←Older revision

Revision as of 04:07, 18 April 2018

OCA: New page: '''Unreleased structure''' The entry 5zo8 is ON HOLD Authors: Yokoyama, H., Sato, K. Description: Eg5 motor domain in complex with STLC-type inhibitor PVEI0021 (P21 type) [[Category: U...

OCA — Wed, 18 Apr 2018 04:07:25 GMT

New page: '''Unreleased structure''' The entry 5zo8 is ON HOLD Authors: Yokoyama, H., Sato, K. Description: Eg5 motor domain in complex with STLC-type inhibitor PVEI0021 (P21 type) [[Category: U...

New page

'''Unreleased structure'''

The entry 5zo8 is ON HOLD

Authors: Yokoyama, H., Sato, K.

Description: Eg5 motor domain in complex with STLC-type inhibitor PVEI0021 (P21 type)
[[Category: Unreleased Structures]]
[[Category: Yokoyama, H]]
[[Category: Sato, K]]