2h4j: Difference between revisions
No edit summary |
No edit summary |
||
| Line 4: | Line 4: | ||
|PDB= 2h4j |SIZE=350|CAPTION= <scene name='initialview01'>2h4j</scene>, resolution 2.10Å | |PDB= 2h4j |SIZE=350|CAPTION= <scene name='initialview01'>2h4j</scene>, resolution 2.10Å | ||
|SITE= | |SITE= | ||
|LIGAND= | |LIGAND= <scene name='pdbligand=NCA:NICOTINAMIDE'>NCA</scene>, <scene name='pdbligand=OAD:2'-O-ACETYL+ADENOSINE-5-DIPHOSPHORIBOSE'>OAD</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene> | ||
|ACTIVITY= | |ACTIVITY= | ||
|GENE= npdA ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=2336 Thermotoga maritima]) | |GENE= npdA ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=2336 Thermotoga maritima]) | ||
|DOMAIN= | |||
|RELATEDENTRY=[[2h4f|2H4F]], [[2h4h|2H4H]] | |||
|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2h4j FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2h4j OCA], [http://www.ebi.ac.uk/pdbsum/2h4j PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=2h4j RCSB]</span> | |||
}} | }} | ||
| Line 14: | Line 17: | ||
==Overview== | ==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. | 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== | ==About this Structure== | ||
| Line 29: | Line 29: | ||
[[Category: Sens, K.]] | [[Category: Sens, K.]] | ||
[[Category: Wolberger, C.]] | [[Category: Wolberger, C.]] | ||
[[Category: rossman fold]] | [[Category: rossman fold]] | ||
[[Category: zn binding domain]] | [[Category: zn binding domain]] | ||
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 03:25:21 2008'' | ||
Revision as of 03:25, 31 March 2008
| |||||||
| , resolution 2.10Å | |||||||
|---|---|---|---|---|---|---|---|
| Ligands: | , , | ||||||
| Gene: | npdA (Thermotoga maritima) | ||||||
| Related: | 2H4F, 2H4H
| ||||||
| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
Sir2-deacetylated peptide (from enzymatic turnover in crystal)
OverviewOverview
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 StructureAbout this Structure
2H4J is a Protein complex structure of sequences from Thermotoga maritima. Full crystallographic information is available from OCA.
ReferenceReference
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 Mon Mar 31 03:25:21 2008