1rqd

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[[Image:1rqd.gif|left|200px]]
 
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==deoxyhypusine synthase holoenzyme in its low ionic strength, high pH crystal form with the inhibitor GC7 bound in the active site==
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The line below this paragraph, containing "STRUCTURE_1rqd", creates the "Structure Box" on the page.
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<StructureSection load='1rqd' size='340' side='right'caption='[[1rqd]], [[Resolution|resolution]] 3.00&Aring;' scene=''>
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You may change the PDB parameter (which sets the PDB file loaded into the applet)
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== Structural highlights ==
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or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
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<table><tr><td colspan='2'>[[1rqd]] 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=1RQD OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1RQD FirstGlance]. <br>
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or leave the SCENE parameter empty for the default display.
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 3&#8491;</td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GC7:1-GUANIDINIUM-7-AMINOHEPTANE'>GC7</scene>, <scene name='pdbligand=NAD:NICOTINAMIDE-ADENINE-DINUCLEOTIDE'>NAD</scene></td></tr>
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{{STRUCTURE_1rqd| PDB=1rqd | SCENE= }}
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1rqd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1rqd OCA], [https://pdbe.org/1rqd PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1rqd RCSB], [https://www.ebi.ac.uk/pdbsum/1rqd PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1rqd ProSAT]</span></td></tr>
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</table>
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== Function ==
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[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.
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== Evolutionary Conservation ==
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[[Image:Consurf_key_small.gif|200px|right]]
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Check<jmol>
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<jmolCheckbox>
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<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/rq/1rqd_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
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<text>to colour the structure by Evolutionary Conservation</text>
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</jmolCheckbox>
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</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=1rqd ConSurf].
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<div style="clear:both"></div>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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Deoxyhypusine synthase catalyzes the first step in the two-step post-translational synthesis of hypusine, which is uniquely present in eukaryotic initiation factor 5A (eIF5A). Deoxyhypusine synthase and eIF5A are conserved throughout the eukaryotic kingdom, and both are essential for cell proliferation and survival. A previous study (Liao, D. I., Wolff, E. C., Park, M. H., and Davies, D. R. (1998) Structure 6, 23-32) of human deoxyhypusine synthase revealed four active sites of the homotetrameric enzyme located within deep tunnels. These Form I crystals were obtained under conditions of acidic pH and high ionic strength and likely contain an inactive enzyme. Each active-site entrance is blocked by a ball-and-chain motif composed of a region of extended structure capped by a two-turn alpha-helix. We report here at 2.2 A a new Form II crystal of the deoxyhypusine synthase:NAD holoenzyme grown at low ionic strength and pH 8.0, near the optimal pH for enzymatic activity. The ball-and-chain motif could not be detected in the electron density, suggesting that it swings freely and thus it no longer obstructs the active-site entrance. The deoxyhypusine synthase competitive inhibitor N(1)-guanyl-1,7-diaminoheptane (GC(7))is observed bound within the putative active site of the enzyme in the new crystal form (Form II) after exposure to the inhibitor. This first structure of a deoxyhypusine synthase.NAD.inhibitor ternary complex under physiological conditions now provides a structural context to discuss the results of previous biochemical investigations of the deoxyhypusine synthase reaction mechanism. This structure also provides a basis for the development of improved inhibitors and antiproliferative agents.
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'''deoxyhypusine synthase holoenzyme in its low ionic strength, high pH crystal form with the inhibitor GC7 bound in the active site'''
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A new crystal structure of deoxyhypusine synthase reveals the configuration of the active enzyme and of an enzyme.NAD.inhibitor ternary complex.,Umland TC, Wolff EC, Park MH, Davies DR J Biol Chem. 2004 Jul 2;279(27):28697-705. Epub 2004 Apr 20. PMID:15100216<ref>PMID:15100216</ref>
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==Overview==
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Deoxyhypusine synthase catalyzes the first step in the two-step post-translational synthesis of hypusine, which is uniquely present in eukaryotic initiation factor 5A (eIF5A). Deoxyhypusine synthase and eIF5A are conserved throughout the eukaryotic kingdom, and both are essential for cell proliferation and survival. A previous study (Liao, D. I., Wolff, E. C., Park, M. H., and Davies, D. R. (1998) Structure 6, 23-32) of human deoxyhypusine synthase revealed four active sites of the homotetrameric enzyme located within deep tunnels. These Form I crystals were obtained under conditions of acidic pH and high ionic strength and likely contain an inactive enzyme. Each active-site entrance is blocked by a ball-and-chain motif composed of a region of extended structure capped by a two-turn alpha-helix. We report here at 2.2 A a new Form II crystal of the deoxyhypusine synthase:NAD holoenzyme grown at low ionic strength and pH 8.0, near the optimal pH for enzymatic activity. The ball-and-chain motif could not be detected in the electron density, suggesting that it swings freely and thus it no longer obstructs the active-site entrance. The deoxyhypusine synthase competitive inhibitor N(1)-guanyl-1,7-diaminoheptane (GC(7))is observed bound within the putative active site of the enzyme in the new crystal form (Form II) after exposure to the inhibitor. This first structure of a deoxyhypusine synthase.NAD.inhibitor ternary complex under physiological conditions now provides a structural context to discuss the results of previous biochemical investigations of the deoxyhypusine synthase reaction mechanism. This structure also provides a basis for the development of improved inhibitors and antiproliferative agents.
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==About this Structure==
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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1RQD is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1RQD OCA].
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</div>
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<div class="pdbe-citations 1rqd" style="background-color:#fffaf0;"></div>
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==Reference==
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==See Also==
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A new crystal structure of deoxyhypusine synthase reveals the configuration of the active enzyme and of an enzyme.NAD.inhibitor ternary complex., Umland TC, Wolff EC, Park MH, Davies DR, J Biol Chem. 2004 Jul 2;279(27):28697-705. Epub 2004 Apr 20. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/15100216 15100216]
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*[[Deoxyhypusine synthase|Deoxyhypusine synthase]]
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[[Category: Deoxyhypusine synthase]]
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== References ==
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<references/>
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__TOC__
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</StructureSection>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: Single protein]]
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[[Category: Large Structures]]
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[[Category: Davies, D R.]]
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[[Category: Davies DR]]
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[[Category: Park, M H.]]
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[[Category: Park M-H]]
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[[Category: Umland, T C.]]
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[[Category: Umland TC]]
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[[Category: Wolff, E C.]]
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[[Category: Wolff EC]]
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[[Category: Deoxyhypusine]]
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[[Category: Gc7]]
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[[Category: Hypusine]]
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[[Category: Nad cofactor]]
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[[Category: Rossman fold]]
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[[Category: Spermidine]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 07:47:23 2008''
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Current revision

deoxyhypusine synthase holoenzyme in its low ionic strength, high pH crystal form with the inhibitor GC7 bound in the active site

PDB ID 1rqd

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