2h5l

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[[Image:2h5l.jpg|left|200px]]<br /><applet load="2h5l" size="350" color="white" frame="true" align="right" spinBox="true"
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[[Image:2h5l.jpg|left|200px]]
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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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{{Structure
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|PDB= 2h5l |SIZE=350|CAPTION= <scene name='initialview01'>2h5l</scene>, resolution 2.8&Aring;
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|SITE=
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|LIGAND= <scene name='pdbligand=NAD:NICOTINAMIDE-ADENINE-DINUCLEOTIDE'>NAD</scene> and <scene name='pdbligand=3DD:(2R,3R)-4-(4-AMINO-1H-IMIDAZO[4,5-C]PYRIDIN-1-YL)-2,3-DIHYDROXYBUTANOIC ACID'>3DD</scene>
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|ACTIVITY= [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]
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|GENE= Ahcy ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10116 Rattus norvegicus])
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}}
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'''S-Adenosylhomocysteine hydrolase containing NAD and 3-deaza-D-eritadenine'''
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==Overview==
==Overview==
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==About this Structure==
==About this Structure==
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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 <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].
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2H5L is a [[Single protein]] structure of sequence from [http://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].
==Reference==
==Reference==
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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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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://www.ncbi.nlm.nih.gov/pubmed/17214973 17214973]
[[Category: Adenosylhomocysteinase]]
[[Category: Adenosylhomocysteinase]]
[[Category: Rattus norvegicus]]
[[Category: Rattus norvegicus]]
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[[Category: s-adenosylhomocysteine]]
[[Category: s-adenosylhomocysteine]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 17:38:23 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 17:12:53 2008''

Revision as of 15:12, 20 March 2008

Image:2h5l.jpg


PDB ID 2h5l

Drag the structure with the mouse to rotate
, resolution 2.8Å
Ligands: and
Gene: Ahcy (Rattus norvegicus)
Activity: Adenosylhomocysteinase, with EC number 3.3.1.1
Coordinates: save as pdb, mmCIF, xml



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


Overview

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.

About this Structure

2H5L is a Single protein structure of sequence from Rattus norvegicus. Full crystallographic information is available from OCA.

Reference

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:17214973

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