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1rqd

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Revision as of 12:55, 10 September 2015

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

Structural highlights

1rqd is a 2 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	,
Related:	1dhs, 1rlz, 1roz
Gene:	DHPS, DS (HUMAN)
Activity:	Transferase, with EC number 2.5.1.46
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum

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

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.

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^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Umland TC, Wolff EC, Park MH, Davies DR. A new crystal structure of deoxyhypusine synthase reveals the configuration of the active enzyme and of an enzyme.NAD.inhibitor ternary complex. J Biol Chem. 2004 Jul 2;279(27):28697-705. Epub 2004 Apr 20. PMID:15100216 doi:10.1074/jbc.M404095200

1 Structural highlights
2 Function
3 Evolutionary Conservation
4 Publication Abstract from PubMed
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/1rqd"

@@ Line 7: / Line 7: @@
 <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">DHPS, DS ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1rqd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1rqd OCA], [http://www.rcsb.org/pdb/explore.do?structureId=1rqd RCSB], [http://www.ebi.ac.uk/pdbsum/1rqd PDBsum]</span></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=1rqd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1rqd OCA], [http://pdbe.org/1rqd PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1rqd RCSB], [http://www.ebi.ac.uk/pdbsum/1rqd PDBsum]</span></td></tr>
 </table>
 == Function ==
@@ Line 29: / Line 29: @@
 From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 </div>
+<div class="pdbe-citations 1rqd" style="background-color:#fffaf0;"></div>
 == References ==
 <references/>

1rqd

From Proteopedia

Revision as of 12:55, 10 September 2015

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

Structural highlights

Function

Evolutionary Conservation

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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