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==CRYSTAL STRUCTURE OF DEOXYHYPUSINE SYNTHASE FROM PYROCOCCUS HORIKOSHII== | ==CRYSTAL STRUCTURE OF DEOXYHYPUSINE SYNTHASE FROM PYROCOCCUS HORIKOSHII== | ||
<StructureSection load='7cmc' size='340' side='right'caption='[[7cmc]]' scene=''> | <StructureSection load='7cmc' size='340' side='right'caption='[[7cmc]], [[Resolution|resolution]] 2.20Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>This structure supersedes the now removed PDB entry [http://oca.weizmann.ac.il/oca-bin/send-pdb?obs=1&id=4p63 4p63]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7CMC OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=7CMC FirstGlance]. <br> | <table><tr><td colspan='2'>[[7cmc]] is a 4 chain structure. This structure supersedes the now removed PDB entry [http://oca.weizmann.ac.il/oca-bin/send-pdb?obs=1&id=4p63 4p63]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7CMC OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=7CMC 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=7cmc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7cmc OCA], [http://pdbe.org/7cmc PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=7cmc RCSB], [http://www.ebi.ac.uk/pdbsum/7cmc PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=7cmc 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=NAD:NICOTINAMIDE-ADENINE-DINUCLEOTIDE'>NAD</scene></td></tr> | ||
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Transferase Transferase], with EC number [http://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'>[http://proteopedia.org/fgij/fg.htm?mol=7cmc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7cmc OCA], [http://pdbe.org/7cmc PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=7cmc RCSB], [http://www.ebi.ac.uk/pdbsum/7cmc PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=7cmc ProSAT]</span></td></tr> | |||
</table> | </table> | ||
== Function == | |||
[[http://www.uniprot.org/uniprot/DHYS_PYRHO DHYS_PYRHO]] 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 == | |||
The eukaryotic and archaeal translation factor IF5A requires a post-translational hypusine modification, which is catalyzed by deoxyhypusine synthase (DHS) at a single lysine residue of IF5A with NAD(+) and spermidine as cofactors, followed by hydroxylation to form hypusine. While human DHS catalyzed reactions have been well characterized, the mechanism of the hypusination of archaeal IF5A by DHS is not clear. Here we report a DHS structure from Pyrococcus horikoshii OT3 (PhoDHS) at 2.2 A resolution. The structure reveals two states in a single functional unit (tetramer): two NAD(+)-bound monomers with the NAD(+) and spermidine binding sites observed in multi-conformations (closed and open), and two NAD(+)-free monomers. The dynamic loop region V288-P299, in the vicinity of the active site, adopts different positions in the closed and open conformations and is disordered when NAD(+) is absent. Combined with NAD(+) binding analysis, it is clear that PhoDHS can exist in three states: apo, PhoDHS-2 equiv NAD(+), and PhoDHS-4 equiv NAD(+), which are affected by the NAD(+) concentration. Our results demonstrate the dynamic structure of PhoDHS at the NAD(+) and spermidine binding site, with conformational changes that may be the response to the local NAD(+) concentration, and thus fine-tune the regulation of the translation process via the hypusine modification of IF5A. | |||
Flexible NAD(+) Binding in Deoxyhypusine Synthase Reflects the Dynamic Hypusine Modification of Translation Factor IF5A.,Chen M, Gai Z, Okada C, Ye Y, Yu J, Yao M Int J Mol Sci. 2020 Jul 31;21(15). pii: ijms21155509. doi: 10.3390/ijms21155509. PMID:32752130<ref>PMID:32752130</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 7cmc" style="background-color:#fffaf0;"></div> | |||
== References == | |||
<references/> | |||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: Gai | [[Category: Transferase]] | ||
[[Category: Okada C]] | [[Category: Gai, Z Q]] | ||
[[Category: Yao M]] | [[Category: Okada, C]] | ||
[[Category: Yu J]] | [[Category: Yao, M]] | ||
[[Category: Yu, J]] | |||
[[Category: Deoxyhypusine synthase]] | |||
[[Category: If5a]] | |||
[[Category: Nad+]] | |||
Revision as of 13:06, 9 September 2020
CRYSTAL STRUCTURE OF DEOXYHYPUSINE SYNTHASE FROM PYROCOCCUS HORIKOSHIICRYSTAL STRUCTURE OF DEOXYHYPUSINE SYNTHASE FROM PYROCOCCUS HORIKOSHII
Structural highlights
Function[DHYS_PYRHO] 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. Publication Abstract from PubMedThe eukaryotic and archaeal translation factor IF5A requires a post-translational hypusine modification, which is catalyzed by deoxyhypusine synthase (DHS) at a single lysine residue of IF5A with NAD(+) and spermidine as cofactors, followed by hydroxylation to form hypusine. While human DHS catalyzed reactions have been well characterized, the mechanism of the hypusination of archaeal IF5A by DHS is not clear. Here we report a DHS structure from Pyrococcus horikoshii OT3 (PhoDHS) at 2.2 A resolution. The structure reveals two states in a single functional unit (tetramer): two NAD(+)-bound monomers with the NAD(+) and spermidine binding sites observed in multi-conformations (closed and open), and two NAD(+)-free monomers. The dynamic loop region V288-P299, in the vicinity of the active site, adopts different positions in the closed and open conformations and is disordered when NAD(+) is absent. Combined with NAD(+) binding analysis, it is clear that PhoDHS can exist in three states: apo, PhoDHS-2 equiv NAD(+), and PhoDHS-4 equiv NAD(+), which are affected by the NAD(+) concentration. Our results demonstrate the dynamic structure of PhoDHS at the NAD(+) and spermidine binding site, with conformational changes that may be the response to the local NAD(+) concentration, and thus fine-tune the regulation of the translation process via the hypusine modification of IF5A. Flexible NAD(+) Binding in Deoxyhypusine Synthase Reflects the Dynamic Hypusine Modification of Translation Factor IF5A.,Chen M, Gai Z, Okada C, Ye Y, Yu J, Yao M Int J Mol Sci. 2020 Jul 31;21(15). pii: ijms21155509. doi: 10.3390/ijms21155509. PMID:32752130[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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