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2h5l

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{{STRUCTURE_2h5l| PDB=2h5l | SCENE= }}
{{STRUCTURE_2h5l| PDB=2h5l | SCENE= }}
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'''S-Adenosylhomocysteine hydrolase containing NAD and 3-deaza-D-eritadenine'''
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===S-Adenosylhomocysteine hydrolase containing NAD and 3-deaza-D-eritadenine===
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==Overview==
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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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(as it appears on PubMed at http://www.pubmed.gov), where 17214973 is the PubMed ID number.
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{{ABSTRACT_PUBMED_17214973}}
==About this Structure==
==About this Structure==
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[[Category: Inhibitor]]
[[Category: Inhibitor]]
[[Category: S-adenosylhomocysteine]]
[[Category: S-adenosylhomocysteine]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Jul 28 12:05:17 2008''

Revision as of 09:05, 28 July 2008

Image:2h5l.png

Template:STRUCTURE 2h5l

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

Template:ABSTRACT PUBMED 17214973

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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