1qbg: Difference between revisions
New page: left|200px<br /> <applet load="1qbg" size="450" color="white" frame="true" align="right" spinBox="true" caption="1qbg, resolution 2.3Å" /> '''CRYSTAL STRUCTURE OF... |
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[[Image:1qbg.gif|left|200px]]<br /> | [[Image:1qbg.gif|left|200px]]<br /><applet load="1qbg" size="350" color="white" frame="true" align="right" spinBox="true" | ||
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caption="1qbg, resolution 2.3Å" /> | caption="1qbg, resolution 2.3Å" /> | ||
'''CRYSTAL STRUCTURE OF HUMAN DT-DIAPHORASE (NAD(P)H OXIDOREDUCTASE)'''<br /> | '''CRYSTAL STRUCTURE OF HUMAN DT-DIAPHORASE (NAD(P)H OXIDOREDUCTASE)'''<br /> | ||
==Overview== | ==Overview== | ||
The crystal structure of human DT-diaphorase (NAD(P)H oxidoreductase | The crystal structure of human DT-diaphorase (NAD(P)H oxidoreductase (quinone); EC 1.6.99.2) has been determined to 2.3 A resolution. There are only minor differences in shape and volume between the active sites of the rat and human enzymes and in the hydrophobic environment in the vicinity of the substrate. The isoalloxazine ring of the bound FAD is more buried in the human structure. Molecular modeling was used to examine optimal positions for the antitumor prodrug CB1954 (5-(aziridin-1-yl)-2,4-dinitrobenzamide) in both the human and rat enzyme active sites. This suggests that the position of CB1954 in the active site of the human enzyme is very similar to that in the rat, although there are detailed differences in the predicted patterns of hydrogen bonding between side chains and the drug. Some of the differences are a consequence of the shift in position for the FAD molecule and may contribute to the observed differences in rate of the two-electron reduction of CB1954. | ||
==Disease== | ==Disease== | ||
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==About this Structure== | ==About this Structure== | ||
1QBG is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with FAD as [http://en.wikipedia.org/wiki/ligand ligand]. Active as [http://en.wikipedia.org/wiki/NAD(P)H_dehydrogenase_(quinone) NAD(P)H dehydrogenase (quinone)], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.6.5.2 1.6.5.2] Full crystallographic information is available from [http:// | 1QBG is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=FAD:'>FAD</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Active as [http://en.wikipedia.org/wiki/NAD(P)H_dehydrogenase_(quinone) NAD(P)H dehydrogenase (quinone)], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.6.5.2 1.6.5.2] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1QBG OCA]. | ||
==Reference== | ==Reference== | ||
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[[Category: Baumann, U.]] | [[Category: Baumann, U.]] | ||
[[Category: Bennett, M.]] | [[Category: Bennett, M.]] | ||
[[Category: Gregory, D | [[Category: Gregory, D S.]] | ||
[[Category: Hobbs, S | [[Category: Hobbs, S M.]] | ||
[[Category: Neidle, S.]] | [[Category: Neidle, S.]] | ||
[[Category: Sanderson, M | [[Category: Sanderson, M R.]] | ||
[[Category: Skelly, J | [[Category: Skelly, J V.]] | ||
[[Category: Suter, D | [[Category: Suter, D A.]] | ||
[[Category: FAD]] | [[Category: FAD]] | ||
[[Category: dt-diaphorase]] | [[Category: dt-diaphorase]] | ||
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[[Category: quinone]] | [[Category: quinone]] | ||
''Page seeded by [http:// | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 14:37:55 2008'' | ||
Revision as of 15:37, 21 February 2008
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CRYSTAL STRUCTURE OF HUMAN DT-DIAPHORASE (NAD(P)H OXIDOREDUCTASE)
OverviewOverview
The crystal structure of human DT-diaphorase (NAD(P)H oxidoreductase (quinone); EC 1.6.99.2) has been determined to 2.3 A resolution. There are only minor differences in shape and volume between the active sites of the rat and human enzymes and in the hydrophobic environment in the vicinity of the substrate. The isoalloxazine ring of the bound FAD is more buried in the human structure. Molecular modeling was used to examine optimal positions for the antitumor prodrug CB1954 (5-(aziridin-1-yl)-2,4-dinitrobenzamide) in both the human and rat enzyme active sites. This suggests that the position of CB1954 in the active site of the human enzyme is very similar to that in the rat, although there are detailed differences in the predicted patterns of hydrogen bonding between side chains and the drug. Some of the differences are a consequence of the shift in position for the FAD molecule and may contribute to the observed differences in rate of the two-electron reduction of CB1954.
DiseaseDisease
Known diseases associated with this structure: Benzene toxicity, susceptibility to OMIM:[125860], Leukemia, post-chemotherapy, susceptibility to OMIM:[125860]
About this StructureAbout this Structure
1QBG is a Single protein structure of sequence from Homo sapiens with as ligand. Active as NAD(P)H dehydrogenase (quinone), with EC number 1.6.5.2 Full crystallographic information is available from OCA.
ReferenceReference
Crystal structure of human DT-diaphorase: a model for interaction with the cytotoxic prodrug 5-(aziridin-1-yl)-2,4-dinitrobenzamide (CB1954)., Skelly JV, Sanderson MR, Suter DA, Baumann U, Read MA, Gregory DS, Bennett M, Hobbs SM, Neidle S, J Med Chem. 1999 Oct 21;42(21):4325-30. PMID:10543876
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