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[[Image:2h5l.jpg|left|200px]]<br /><applet load="2h5l" size="350" color="white" frame="true" align="right" spinBox="true"
caption="2h5l, resolution 2.8&Aring;" />
'''S-Adenosylhomocysteine hydrolase containing NAD and 3-deaza-D-eritadenine'''<br />


==Overview==
==S-Adenosylhomocysteine hydrolase containing NAD and 3-deaza-D-eritadenine==
d-Eritadenine (DEA) is a potent inhibitor of S-adenosyl-l-homocysteine hydrolase (SAHH) and has hypocholesterolemic activity. We have hypothesized that 3-deaza-DEA (C3-DEA) and its analogues retain high level of SAHH inhibitory activity and have resistance to deamination and glycosidic bond hydrolysis in vivo. Such C3-DEA analogues would have much higher hypocholesterolemic activity. C3-DEA, and its methyl ester (C3-OMeDEA) and its methyl amido (C3-NMeDEA) were synthesized to examine their SAHH inhibitory and hypocholesterolemic activities. A crystal structure of SAHH containing C3-DEA was determined and confirmed that DEA and C3-DEA bound to the same site of SAHH with the same binding mode. The SAHH inhibitory activities of C3-DEA (K(I)=1.5 microM) and C3-OMeDEA (K(I)=1.5 microM) are significantly lower than that of DEA (K(I)=30 nM), while rats fed by C3-DEA and C3-OMeDEA decrease the total plasma cholesterol and phospholipids by 36-40% and 23%, respectively, which is similar to the level of reductions (42% and 27%) by DEA. C3-NMeDEA lost most of the SAHH inhibitory activity (K(I)=30 microM) and dietary C3-NMeDEA does not decrease cholesterol and phospholipid in plasma but decreases the triacylglycerol level by 16%. DEA and C3-DEA analogues are neither substrates nor inhibitors of adenosine deaminase.
<StructureSection load='2h5l' size='340' side='right'caption='[[2h5l]], [[Resolution|resolution]] 2.80&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[2h5l]] is a 8 chain structure with sequence from [https://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2H5L OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2H5L FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.8&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=3DD:(2R,3R)-4-(4-AMINO-1H-IMIDAZO[4,5-C]PYRIDIN-1-YL)-2,3-DIHYDROXYBUTANOIC+ACID'>3DD</scene>, <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'>[https://proteopedia.org/fgij/fg.htm?mol=2h5l FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2h5l OCA], [https://pdbe.org/2h5l PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2h5l RCSB], [https://www.ebi.ac.uk/pdbsum/2h5l PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2h5l ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/SAHH_RAT SAHH_RAT] Adenosylhomocysteine is a competitive inhibitor of S-adenosyl-L-methionine-dependent methyl transferase reactions; therefore adenosylhomocysteinase may play a key role in the control of methylations via regulation of the intracellular concentration of adenosylhomocysteine.
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
Check<jmol>
  <jmolCheckbox>
    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/h5/2h5l_consurf.spt"</scriptWhenChecked>
    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
    <text>to colour the structure by Evolutionary Conservation</text>
  </jmolCheckbox>
</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=2h5l ConSurf].
<div style="clear:both"></div>


==About this Structure==
==See Also==
2H5L is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus] with <scene name='pdbligand=NAD:'>NAD</scene> and <scene name='pdbligand=3DD:'>3DD</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Adenosylhomocysteinase Adenosylhomocysteinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.3.1.1 3.3.1.1] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2H5L OCA].
*[[S-adenosylhomocysteine hydrolase|S-adenosylhomocysteine hydrolase]]
 
__TOC__
==Reference==
</StructureSection>
Structure and function of eritadenine and its 3-deaza analogues: potent inhibitors of S-adenosylhomocysteine hydrolase and hypocholesterolemic agents., Yamada T, Komoto J, Lou K, Ueki A, Hua DH, Sugiyama K, Takata Y, Ogawa H, Takusagawa F, Biochem Pharmacol. 2007 Apr 1;73(7):981-9. Epub 2006 Dec 14. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=17214973 17214973]
[[Category: Large Structures]]
[[Category: Adenosylhomocysteinase]]
[[Category: Rattus norvegicus]]
[[Category: Rattus norvegicus]]
[[Category: Single protein]]
[[Category: Komoto J]]
[[Category: Komoto, J.]]
[[Category: Takusagawa F]]
[[Category: Takusagawa, F.]]
[[Category: Yamada T]]
[[Category: Yamada, T.]]
[[Category: 3DD]]
[[Category: NAD]]
[[Category: hydrolase]]
[[Category: hypocholesterolemic activity]]
[[Category: inhibitor]]
[[Category: s-adenosylhomocysteine]]
 
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Retrieved from "https://proteopedia.org/2h5l"