2h4h
From Proteopedia
| Line 1: | Line 1: | ||
[[Image:2h4h.gif|left|200px]] | [[Image:2h4h.gif|left|200px]] | ||
| - | + | <!-- | |
| - | + | The line below this paragraph, containing "STRUCTURE_2h4h", creates the "Structure Box" on the page. | |
| - | + | You may change the PDB parameter (which sets the PDB file loaded into the applet) | |
| - | + | or the SCENE parameter (which sets the initial scene displayed when the page is loaded), | |
| - | | | + | or leave the SCENE parameter empty for the default display. |
| - | | | + | --> |
| - | + | {{STRUCTURE_2h4h| PDB=2h4h | SCENE= }} | |
| - | + | ||
| - | + | ||
| - | }} | + | |
'''Sir2 H116Y mutant-p53 peptide-NAD''' | '''Sir2 H116Y mutant-p53 peptide-NAD''' | ||
| Line 29: | Line 26: | ||
[[Category: Sens, K.]] | [[Category: Sens, K.]] | ||
[[Category: Wolberger, C.]] | [[Category: Wolberger, C.]] | ||
| - | [[Category: | + | [[Category: Rossmann fold]] |
| - | [[Category: | + | [[Category: Zn-binding domain]] |
| - | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun May 4 05:51:19 2008'' | |
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | |
Revision as of 02:51, 4 May 2008
Sir2 H116Y mutant-p53 peptide-NAD
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.
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 Sun May 4 05:51:19 2008
