2h5l: Difference between revisions
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'''S-Adenosylhomocysteine hydrolase containing NAD and 3-deaza-D-eritadenine''' | {{Structure | ||
|PDB= 2h5l |SIZE=350|CAPTION= <scene name='initialview01'>2h5l</scene>, resolution 2.8Å | |||
|SITE= | |||
|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> | |||
|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] | |||
|GENE= Ahcy ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10116 Rattus norvegicus]) | |||
}} | |||
'''S-Adenosylhomocysteine hydrolase containing NAD and 3-deaza-D-eritadenine''' | |||
==Overview== | ==Overview== | ||
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==About this Structure== | ==About this Structure== | ||
2H5L is a [ | 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== | ||
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:// | 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]] | ||
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu | ''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
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| 2h5l, resolution 2.8Å | |||||||||||||
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| Ligands: | NAD and 3DD | ||||||||||||
| 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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