This old version of Proteopedia is provided for student assignments while the new version is undergoing repairs. Content and edits done in this old version of Proteopedia after March 1, 2026 will eventually be lost when it is retired in about June of 2026.

Apply for new accounts at the new Proteopedia. Your logins will work in both the old and new versions.


2h5l

From Proteopedia

(Difference between revisions)
Jump to: navigation, search
(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...)
Current revision (09:31, 14 February 2024) (edit) (undo)
 
(14 intermediate revisions not shown.)
Line 1: Line 1:
-
[[Image:2h5l.jpg|left|200px]]<br /><applet load="2h5l" size="450" 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 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].
+
*[[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]]
+
-
 
+
-
''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Wed Nov 21 11:33:13 2007''
+

Current revision

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

PDB ID 2h5l

Drag the structure with the mouse to rotate

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/2h5l"
Personal tools