3d4b

From Proteopedia

(Difference between revisions)

Revision as of 13:11, 25 December 2014

Crystal structure of Sir2Tm in complex with Acetyl p53 peptide and DADMe-NAD+

Structural highlights

3d4b is a 2 chain structure with sequence from Thermotoga maritima. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	,
NonStd Res:
Gene:	npdA, TM_0490 (Thermotoga maritima)
Resources:	FirstGlance, OCA, RCSB, PDBsum

Function

[NPD_THEMA] NAD-dependent protein deacetylase which modulates the activities of several enzymes which are inactive in their acetylated form. Has also depropionylation activity in vitro. Also able to ADP-ribosylate peptide substrates with Arg or Lys in the +2 position. The role of this function in vivo is not clear.^[1] ^[2] ^[3]

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

Publication Abstract from PubMed

Sirtuin enzymes comprise a unique class of NAD(+)-dependent protein deacetylases. Although structures of many sirtuin complexes have been determined, structural resolution of intermediate chemical steps are needed to understand the deacetylation mechanism. We report crystal structures of the bacterial sirtuin, Sir2Tm, in complex with an S-alkylamidate intermediate, analogous to the naturally occurring O-alkylamidate intermediate, and a Sir2Tm ternary complex containing a dissociated NAD(+) analog and acetylated peptide. The structures and biochemical studies reveal critical roles for the invariant active site histidine in positioning the reaction intermediate, and for a conserved phenylalanine residue in shielding reaction intermediates from base exchange with nicotinamide. The new structural and biochemical studies provide key mechanistic insight into intermediate steps of the Sir2 deacetylation reaction.

Structural insights into intermediate steps in the Sir2 deacetylation reaction.,Hawse WF, Hoff KG, Fatkins DG, Daines A, Zubkova OV, Schramm VL, Zheng W, Wolberger C Structure. 2008 Sep 10;16(9):1368-77. PMID:18786399^[4]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Garrity J, Gardner JG, Hawse W, Wolberger C, Escalante-Semerena JC. N-lysine propionylation controls the activity of propionyl-CoA synthetase. J Biol Chem. 2007 Oct 12;282(41):30239-45. Epub 2007 Aug 7. PMID:17684016 doi:10.1074/jbc.M704409200
↑ Hoff KG, Avalos JL, Sens K, Wolberger C. Insights into the sirtuin mechanism from ternary complexes containing NAD+ and acetylated peptide. Structure. 2006 Aug;14(8):1231-40. PMID:16905097 doi:http://dx.doi.org/10.1016/j.str.2006.06.006
↑ Hawse WF, Wolberger C. Structure-based mechanism of ADP-ribosylation by sirtuins. J Biol Chem. 2009 Nov 27;284(48):33654-61. Epub 2009 Sep 30. PMID:19801667 doi:10.1074/jbc.M109.024521
↑ Hawse WF, Hoff KG, Fatkins DG, Daines A, Zubkova OV, Schramm VL, Zheng W, Wolberger C. Structural insights into intermediate steps in the Sir2 deacetylation reaction. Structure. 2008 Sep 10;16(9):1368-77. PMID:18786399 doi:10.1016/j.str.2008.05.015

1 Structural highlights
2 Function
3 Evolutionary Conservation
4 Publication Abstract from PubMed
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/3d4b"

@@ Line 8: / Line 8: @@
 <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3d4b FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3d4b OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3d4b RCSB], [http://www.ebi.ac.uk/pdbsum/3d4b PDBsum]</span></td></tr>
 </table>
+== Function ==
+[[http://www.uniprot.org/uniprot/NPD_THEMA NPD_THEMA]] NAD-dependent protein deacetylase which modulates the activities of several enzymes which are inactive in their acetylated form. Has also depropionylation activity in vitro. Also able to ADP-ribosylate peptide substrates with Arg or Lys in the +2 position. The role of this function in vivo is not clear.<ref>PMID:17684016</ref> <ref>PMID:16905097</ref> <ref>PMID:19801667</ref>
 == Evolutionary Conservation ==
 [[Image:Consurf_key_small.gif|200px|right]]

3d4b

From Proteopedia

Revision as of 13:11, 25 December 2014

Crystal structure of Sir2Tm in complex with Acetyl p53 peptide and DADMe-NAD+

Structural highlights

Function

Evolutionary Conservation

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

Personal tools

Navigation

Search

Toolbox