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| | <StructureSection load='1dhs' size='340' side='right'caption='[[1dhs]], [[Resolution|resolution]] 2.20Å' scene=''> | | <StructureSection load='1dhs' size='340' side='right'caption='[[1dhs]], [[Resolution|resolution]] 2.20Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[1dhs]] is a 1 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=1DHS OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1DHS FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[1dhs]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1DHS OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1DHS FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=NAD:NICOTINAMIDE-ADENINE-DINUCLEOTIDE'>NAD</scene></td></tr> | + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=NAD:NICOTINAMIDE-ADENINE-DINUCLEOTIDE'>NAD</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=1dhs FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1dhs OCA], [http://pdbe.org/1dhs PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1dhs RCSB], [http://www.ebi.ac.uk/pdbsum/1dhs PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=1dhs ProSAT]</span></td></tr> | + | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Transferase Transferase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.5.1.46 2.5.1.46] </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=1dhs FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1dhs OCA], [https://pdbe.org/1dhs PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1dhs RCSB], [https://www.ebi.ac.uk/pdbsum/1dhs PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1dhs ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://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. | + | [[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. |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
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| | </div> | | </div> |
| | <div class="pdbe-citations 1dhs" style="background-color:#fffaf0;"></div> | | <div class="pdbe-citations 1dhs" style="background-color:#fffaf0;"></div> |
| | + | |
| | + | ==See Also== |
| | + | *[[Deoxyhypusine synthase|Deoxyhypusine synthase]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
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| | [[Category: Human]] | | [[Category: Human]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| | + | [[Category: Transferase]] |
| | [[Category: Davies, D R]] | | [[Category: Davies, D R]] |
| | [[Category: Liao, D I]] | | [[Category: Liao, D I]] |
| Structural highlights
Function
[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.
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
BACKGROUND: Eukaryotic initiation factor 5A (elF-5A) contains an unusual amino acid, hypusine [N epsilon-(4-aminobutyl-2-hydroxy)lysine]. The first step in the post-translational formation of hypusine is catalysed by the enzyme deoxyhypusine synthase (DHS). The modified version of elF-5A, and DHS, are required for eukaryotic cell proliferation. Knowledge of the three-dimensional structure of this key enzyme should permit the design of specific inhibitors that may be useful as anti-proliferative agents. RESULTS: The crystal structure of human DHS with bound NAD cofactor has been determined and refined at 2.2 A resolution. The enzyme is a tetramer of four identical subunits arranged with 222 symmetry; each subunit contains a nucleotide-binding (or Rossmann) fold. The tetramer comprises two tightly associated dimers and contains four active sites, two in each dimer interface. The catalytic portion of each active site is located in one subunit while the NAD-binding site is located in the other. The entrance to the active-site cavity is blocked by a two-turn alpha helix, part of a third subunit, to which it is joined by an extended loop. CONCLUSIONS: The active site of DHS is a cavity buried below the surface of the enzyme at the interface between two subunits. In the conformation observed here, the substrate-binding site is inaccessible and we propose that the reaction steps carried out by the enzyme must be accompanied by significant conformational changes, the least of which would be the displacement of the two-turn alpha helix.
Crystal structure of the NAD complex of human deoxyhypusine synthase: an enzyme with a ball-and-chain mechanism for blocking the active site.,Liao DI, Wolff EC, Park MH, Davies DR Structure. 1998 Jan 15;6(1):23-32. PMID:9493264[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Liao DI, Wolff EC, Park MH, Davies DR. Crystal structure of the NAD complex of human deoxyhypusine synthase: an enzyme with a ball-and-chain mechanism for blocking the active site. Structure. 1998 Jan 15;6(1):23-32. PMID:9493264
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