1rlz
From Proteopedia
(New page: 200px<br /> <applet load="1rlz" size="450" color="white" frame="true" align="right" spinBox="true" caption="1rlz, resolution 2.15Å" /> '''Deoxyhypusine synth...) |
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| - | [[Image:1rlz. | + | [[Image:1rlz.jpg|left|200px]]<br /><applet load="1rlz" size="350" color="white" frame="true" align="right" spinBox="true" |
| - | <applet load="1rlz" size=" | + | |
caption="1rlz, resolution 2.15Å" /> | caption="1rlz, resolution 2.15Å" /> | ||
'''Deoxyhypusine synthase holoenzyme in its high ionic strength, low pH crystal form'''<br /> | '''Deoxyhypusine synthase holoenzyme in its high ionic strength, low pH crystal form'''<br /> | ||
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==Disease== | ==Disease== | ||
| - | Known disease associated with this structure: Porokeratosis, disseminated superficial actinic OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id= | + | Known disease associated with this structure: Porokeratosis, disseminated superficial actinic, 1 OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=611684 611684]] |
==About this Structure== | ==About this Structure== | ||
| - | 1RLZ is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with NAD as [http://en.wikipedia.org/wiki/ligand ligand]. Active as [http://en.wikipedia.org/wiki/Deoxyhypusine_synthase Deoxyhypusine synthase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.5.1.46 2.5.1.46] Full crystallographic information is available from [http:// | + | 1RLZ is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=NAD:'>NAD</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Active as [http://en.wikipedia.org/wiki/Deoxyhypusine_synthase Deoxyhypusine synthase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.5.1.46 2.5.1.46] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1RLZ OCA]. |
==Reference== | ==Reference== | ||
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[[Category: spermidine]] | [[Category: spermidine]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri Feb 15 16:49:04 2008'' |
Revision as of 14:49, 15 February 2008
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Deoxyhypusine synthase holoenzyme in its high ionic strength, low pH crystal form
Contents |
Overview
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.
Disease
Known disease associated with this structure: Porokeratosis, disseminated superficial actinic, 1 OMIM:[611684]
About this Structure
1RLZ is a Single protein structure of sequence from Homo sapiens with as ligand. Active as Deoxyhypusine synthase, with EC number 2.5.1.46 Full crystallographic information is available from OCA.
Reference
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
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