2h4h
From Proteopedia
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| - | [[Image:2h4h.gif|left|200px]] | + | [[Image:2h4h.gif|left|200px]] |
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| - | '''Sir2 H116Y mutant-p53 peptide-NAD''' | + | {{Structure |
| + | |PDB= 2h4h |SIZE=350|CAPTION= <scene name='initialview01'>2h4h</scene>, resolution 1.99Å | ||
| + | |SITE= | ||
| + | |LIGAND= <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene> and <scene name='pdbligand=NAD:NICOTINAMIDE-ADENINE-DINUCLEOTIDE'>NAD</scene> | ||
| + | |ACTIVITY= | ||
| + | |GENE= npdA ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=2336 Thermotoga maritima]) | ||
| + | }} | ||
| + | |||
| + | '''Sir2 H116Y mutant-p53 peptide-NAD''' | ||
| + | |||
==Overview== | ==Overview== | ||
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==About this Structure== | ==About this Structure== | ||
| - | 2H4H is a [ | + | 2H4H is a [[Protein complex]] structure of sequences from [http://en.wikipedia.org/wiki/Thermotoga_maritima Thermotoga maritima]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2H4H OCA]. |
==Reference== | ==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:[http:// | + | 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:[http://www.ncbi.nlm.nih.gov/pubmed/16905097 16905097] |
[[Category: Protein complex]] | [[Category: Protein complex]] | ||
[[Category: Thermotoga maritima]] | [[Category: Thermotoga maritima]] | ||
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[[Category: zn-binding domain]] | [[Category: zn-binding domain]] | ||
| - | ''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 17:12:31 2008'' |
Revision as of 15:12, 20 March 2008
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| , resolution 1.99Å | |||||||
|---|---|---|---|---|---|---|---|
| Ligands: | and | ||||||
| Gene: | npdA (Thermotoga maritima) | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
Sir2 H116Y mutant-p53 peptide-NAD
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
2H4H is a Protein complex structure of sequences from Thermotoga maritima. 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 Mar 20 17:12:31 2008
