2h5l

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(New page: 200px<br /><applet load="2h5l" size="450" color="white" frame="true" align="right" spinBox="true" caption="2h5l, resolution 2.8&Aring;" /> '''S-Adenosylhomocystein...)
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[[Image:2h5l.jpg|left|200px]]<br /><applet load="2h5l" size="450" color="white" frame="true" align="right" spinBox="true"
 
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caption="2h5l, resolution 2.8&Aring;" />
 
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'''S-Adenosylhomocysteine hydrolase containing NAD and 3-deaza-D-eritadenine'''<br />
 
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==Overview==
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==S-Adenosylhomocysteine hydrolase containing NAD and 3-deaza-D-eritadenine==
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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.
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<StructureSection load='2h5l' size='340' side='right'caption='[[2h5l]], [[Resolution|resolution]] 2.80&Aring;' scene=''>
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== Structural highlights ==
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<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>
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</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>
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<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>
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<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>
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</table>
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== Function ==
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[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.
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== Evolutionary Conservation ==
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[[Image:Consurf_key_small.gif|200px|right]]
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Check<jmol>
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<jmolCheckbox>
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<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/h5/2h5l_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
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<text>to colour the structure by Evolutionary Conservation</text>
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</jmolCheckbox>
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</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].
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<div style="clear:both"></div>
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==About this Structure==
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==See Also==
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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 NAD and 3DD 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://ispc.weizmann.ac.il/oca-bin/ocashort?id=2H5L OCA].
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*[[S-adenosylhomocysteine hydrolase|S-adenosylhomocysteine hydrolase]]
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__TOC__
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==Reference==
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</StructureSection>
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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]
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[[Category: Large Structures]]
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[[Category: Adenosylhomocysteinase]]
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[[Category: Rattus norvegicus]]
[[Category: Rattus norvegicus]]
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[[Category: Single protein]]
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[[Category: Komoto J]]
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[[Category: Komoto, J.]]
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[[Category: Takusagawa F]]
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[[Category: Takusagawa, F.]]
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[[Category: Yamada T]]
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[[Category: Yamada, T.]]
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[[Category: 3DD]]
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[[Category: NAD]]
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[[Category: hydrolase]]
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[[Category: hypocholesterolemic activity]]
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[[Category: inhibitor]]
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[[Category: s-adenosylhomocysteine]]
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''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Wed Nov 21 11:33:13 2007''
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Current revision

S-Adenosylhomocysteine hydrolase containing NAD and 3-deaza-D-eritadenine

PDB ID 2h5l

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