OCA at 13:14, 24 January 2024

OCA — Wed, 24 Jan 2024 13:14:55 GMT

←Older revision		Revision as of 13:14, 24 January 2024
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	==Crystal Structure of Human Deoxyhypusine Synthase in complex with spermine==		==Crystal Structure of Human Deoxyhypusine Synthase in complex with spermine==
-	<StructureSection load='6xxl' size='340' side='right'caption='[[6xxl]]' scene=''>	+	<StructureSection load='6xxl' size='340' side='right'caption='[[6xxl]], [[Resolution\|resolution]] 1.69Å' 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=6XXL OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://proteopedia.org/fgij/fg.htm?mol=6XXL FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6xxl]] 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=6XXL OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6XXL 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=6xxl FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6xxl OCA], [~~http~~://pdbe.org/6xxl PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=6xxl RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/6xxl PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=6xxl ProSAT]</span></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]] 1.69Å</td></tr>
		+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=BME:BETA-MERCAPTOETHANOL'>BME</scene>, <scene name='pdbligand=CSS:S-MERCAPTOCYSTEINE'>CSS</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=FMT:FORMIC+ACID'>FMT</scene>, <scene name='pdbligand=MPD:(4S)-2-METHYL-2,4-PENTANEDIOL'>MPD</scene>, <scene name='pdbligand=OXM:OXAMIC+ACID'>OXM</scene>, <scene name='pdbligand=SPM:SPERMINE'>SPM</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=6xxl FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6xxl OCA], [https://pdbe.org/6xxl PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6xxl RCSB], [https://www.ebi.ac.uk/pdbsum/6xxl PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6xxl ProSAT]</span></td></tr>
	</table>		</table>
		+	== Function ==
		+	[https://www.uniprot.org/uniprot/DHYS_HUMAN DHYS_HUMAN] Catalyzes the NAD-dependent oxidative cleavage of spermidine and the subsequent transfer of the butylamine moiety of spermidine to the epsilon-amino group of a specific lysine residue of the eIF-5A precursor protein to form the intermediate deoxyhypusine residue.
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Deoxyhypusine synthase (DHS) is a transferase enabling the formation of deoxyhypusine, which is the first, rate-limiting step of a unique post-translational modification: hypusination. DHS catalyses the transfer of a 4-aminobutyl moiety of polyamine spermidine to a specific lysine of eukaryotic translation factor 5A (eIF5A) precursor in a nicotinamide adenine dinucleotide (NAD)-dependent manner. This modification occurs exclusively on one protein, eIF5A, and it is essential for cell proliferation. Malfunctions of the hypusination pathway, including those caused by mutations within the DHS encoding gene, are associated with conditions such as cancer or neurodegeneration. Here, we present a series of high-resolution crystal structures of human DHS. Structures were determined as the apoprotein, as well as ligand-bound states at high-resolutions ranging from 1.41 to 1.69 A. By solving DHS in complex with its natural substrate spermidine (SPD), we identified the mode of substrate recognition. We also observed that other polyamines, namely spermine (SPM) and putrescine, bind DHS in a similar manner as SPD. Moreover, we performed activity assays showing that SPM could to some extent serve as an alternative DHS substrate. In contrast to previous studies, we demonstrate that no conformational changes occur in the DHS structure upon spermidine-binding. By combining mutagenesis and a light-scattering approach, we show that a conserved "ball-and-chain" motif is indispensable to assembling a functional DHS tetramer. Our study substantially advances our knowledge of the substrate recognition mechanism by DHS and may aid the design of pharmacological compounds for potential applications in cancer therapy.
		+
		+	Half Way to Hypusine-Structural Basis for Substrate Recognition by Human Deoxyhypusine Synthase.,Wator E, Wilk P, Grudnik P Biomolecules. 2020 Mar 30;10(4). pii: biom10040522. doi: 10.3390/biom10040522. PMID:32235505<ref>PMID:32235505</ref>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	<div class="pdbe-citations 6xxl" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Deoxyhypusine synthase\|Deoxyhypusine synthase]]
		+	== References ==
		+	<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
	[[Category: Grudnik P]]		[[Category: Grudnik P]]
	[[Category: Wator E]]		[[Category: Wator E]]
	[[Category: Wilk P]]		[[Category: Wilk P]]

OCA at 07:05, 15 April 2020

OCA — Wed, 15 Apr 2020 07:05:29 GMT

←Older revision		Revision as of 07:05, 15 April 2020
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 6xxl ~~is ON HOLD~~	+	==Crystal Structure of Human Deoxyhypusine Synthase in complex with spermine==
-		+	<StructureSection load='6xxl' size='340' side='right'caption='[[6xxl]]' scene=''>
-	~~Authors~~: ~~Wator~~, E., ~~Wilk~~, P., ~~Grudnik~~, P.	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6XXL OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6XXL FirstGlance]. <br>
-	~~Description: Crystal Structure of Human Deoxyhypusine Synthase in complex with spermine~~	+	</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=6xxl FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6xxl OCA], [http://pdbe.org/6xxl PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6xxl RCSB], [http://www.ebi.ac.uk/pdbsum/6xxl PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6xxl ProSAT]</span></td></tr>
-	[[Category: ~~Unreleased~~ Structures]]	+	</table>
-	[[Category: ~~Wilk,~~ P]]	+	__TOC__
-	[[Category: ~~Grudnik, P~~]]	+	</StructureSection>
-	[[Category: ~~Wator, E~~]]	+	[[Category: Large Structures]]
		+	[[Category: Grudnik P]]
		+	[[Category: Wator E]]
		+	[[Category: Wilk P]]

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

OCA — Wed, 05 Feb 2020 06:28:21 GMT

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

←Older revision

Revision as of 06:28, 5 February 2020

OCA: New page: '''Unreleased structure''' The entry 6xxl is ON HOLD Authors: Wator, E., Wilk, P., Grudnik, P. Description: Crystal Structure of Human Deoxyhypusine Synthase in complex with spermine [...

OCA — Wed, 05 Feb 2020 06:28:19 GMT

New page: '''Unreleased structure''' The entry 6xxl is ON HOLD Authors: Wator, E., Wilk, P., Grudnik, P. Description: Crystal Structure of Human Deoxyhypusine Synthase in complex with spermine [...

New page

'''Unreleased structure'''

The entry 6xxl is ON HOLD

Authors: Wator, E., Wilk, P., Grudnik, P.

Description: Crystal Structure of Human Deoxyhypusine Synthase in complex with spermine
[[Category: Unreleased Structures]]
[[Category: Wilk, P]]
[[Category: Grudnik, P]]
[[Category: Wator, E]]

6xxl - Revision history

OCA at 13:14, 24 January 2024

OCA at 07:05, 15 April 2020

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

OCA: New page: '''Unreleased structure''' The entry 6xxl is ON HOLD Authors: Wator, E., Wilk, P., Grudnik, P. Description: Crystal Structure of Human Deoxyhypusine Synthase in complex with spermine [...