2h59
From Proteopedia
(New page: 200px<br /> <applet load="2h59" size="450" color="white" frame="true" align="right" spinBox="true" caption="2h59, resolution 1.90Å" /> '''Sir2 H116A-deacetyl...) |
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| - | [[Image:2h59.gif|left|200px]]<br /> | + | [[Image:2h59.gif|left|200px]]<br /><applet load="2h59" size="350" color="white" frame="true" align="right" spinBox="true" |
| - | <applet load="2h59" size=" | + | |
caption="2h59, resolution 1.90Å" /> | caption="2h59, resolution 1.90Å" /> | ||
'''Sir2 H116A-deacetylated p53 peptide-3'-o-acetyl ADP ribose'''<br /> | '''Sir2 H116A-deacetylated p53 peptide-3'-o-acetyl ADP ribose'''<br /> | ||
==Overview== | ==Overview== | ||
| - | Sirtuin proteins comprise a unique class of NAD+-dependent protein | + | Sirtuin proteins comprise a unique class of NAD+-dependent protein deacetylases. Although several structures of sirtuins have been determined, the mechanism by which NAD+ cleavage occurs has remained unclear. We report the structures of ternary complexes containing NAD+ and acetylated peptide bound to the bacterial sirtuin Sir2Tm and to a catalytic mutant (Sir2Tm(H116Y)). NAD+ in these structures binds in a conformation different from that seen in previous structures, exposing the alpha face of the nicotinamide ribose to the carbonyl oxygen of the acetyl lysine substrate. The NAD+ conformation is identical in both structures, suggesting that proper coenzyme orientation is not dependent on contacts with the catalytic histidine. We also present the structure of Sir2Tm(H116A) bound to deacteylated peptide and 3'-O-acetyl ADP ribose. Taken together, these structures suggest a mechanism for nicotinamide cleavage in which an invariant phenylalanine plays a central role in promoting formation of the O-alkylamidate reaction intermediate and preventing nicotinamide exchange. |
==Disease== | ==Disease== | ||
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==About this Structure== | ==About this Structure== | ||
| - | 2H59 is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Thermotoga_maritima Thermotoga maritima] with ZN, APR and 3OD as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http:// | + | 2H59 is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Thermotoga_maritima Thermotoga maritima] with <scene name='pdbligand=ZN:'>ZN</scene>, <scene name='pdbligand=APR:'>APR</scene> and <scene name='pdbligand=3OD:'>3OD</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2H59 OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Protein complex]] | [[Category: Protein complex]] | ||
[[Category: Thermotoga maritima]] | [[Category: Thermotoga maritima]] | ||
| - | [[Category: Avalos, J | + | [[Category: Avalos, J L.]] |
| - | [[Category: Hoff, K | + | [[Category: Hoff, K G.]] |
[[Category: Sens, K.]] | [[Category: Sens, K.]] | ||
[[Category: Wolberger, C.]] | [[Category: Wolberger, C.]] | ||
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[[Category: zn binding domain]] | [[Category: zn binding domain]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 17:38:19 2008'' |
Revision as of 15:38, 21 February 2008
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Sir2 H116A-deacetylated p53 peptide-3'-o-acetyl ADP ribose
Contents |
Overview
Sirtuin proteins comprise a unique class of NAD+-dependent protein deacetylases. Although several structures of sirtuins have been determined, the mechanism by which NAD+ cleavage occurs has remained unclear. We report the structures of ternary complexes containing NAD+ and acetylated peptide bound to the bacterial sirtuin Sir2Tm and to a catalytic mutant (Sir2Tm(H116Y)). NAD+ in these structures binds in a conformation different from that seen in previous structures, exposing the alpha face of the nicotinamide ribose to the carbonyl oxygen of the acetyl lysine substrate. The NAD+ conformation is identical in both structures, suggesting that proper coenzyme orientation is not dependent on contacts with the catalytic histidine. We also present the structure of Sir2Tm(H116A) bound to deacteylated peptide and 3'-O-acetyl ADP ribose. Taken together, these structures suggest a mechanism for nicotinamide cleavage in which an invariant phenylalanine plays a central role in promoting formation of the O-alkylamidate reaction intermediate and preventing nicotinamide exchange.
Disease
Known diseases associated with this structure: Adrenal cortical carcinoma OMIM:[191170], Breast cancer OMIM:[191170], Colorectal cancer OMIM:[191170], Hepatocellular carcinoma OMIM:[191170], Histiocytoma OMIM:[191170], Li-Fraumeni syndrome OMIM:[191170], Multiple malignancy syndrome OMIM:[191170], Nasopharyngeal carcinoma OMIM:[191170], Osteosarcoma OMIM:[191170], Pancreatic cancer OMIM:[191170], Thyroid carcinoma OMIM:[191170]
About this Structure
2H59 is a Protein complex structure of sequences from Thermotoga maritima with , and as ligands. Full crystallographic information is available from OCA.
Reference
Insights into the sirtuin mechanism from ternary complexes containing NAD+ and acetylated peptide., Hoff KG, Avalos JL, Sens K, Wolberger C, Structure. 2006 Aug;14(8):1231-40. PMID:16905097
Page seeded by OCA on Thu Feb 21 17:38:19 2008
Categories: Protein complex | Thermotoga maritima | Avalos, J L. | Hoff, K G. | Sens, K. | Wolberger, C. | 3OD | APR | ZN | Rossmann fold | Zn binding domain
