3u3d

From Proteopedia

(Difference between revisions)

Revision as of 05:55, 13 July 2022

Plasmodium falciparum Sir2A preferentially hydrolyzes medium and long chain fatty acyl lysine

Structural highlights

3u3d is a 2 chain structure with sequence from Plaf7. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	,
NonStd Res:
Related:	3u31
Gene:	PF13_0152, Sir2 (PLAF7)
Activity:	Acyl-lysine deacylase, with EC number 3.5.1.17
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[SIR5_PLAF7] NAD-dependent protein deacylase. Catalyzes the NAD-dependent hydrolysis of medium and long chain fatty acyl groups from lysine residues. Has weak NAD-dependent protein deacetylase activity; however this activity may not be physiologically relevant in vivo. Regulates the expression of the surface antigen-coding var genes central to the malaria pathogenesis. Cooperates with Sir2B to mediate silencing and mutual exclusive expression of only 1 of the 60 subtelomeric var genes at a time, coding for functionally different but epitopically variant versions of the erythrocyte membrane protein 1 (PfEMP1) molecule, to evade the detection by host immune surveillance. Can ADP-ribosylate both histones and itself. May also have a role in telomeric end protection.^[1] ^[2] ^[3] ^[4] ^[5] ^[6] ^[7] ^[8]

Publication Abstract from PubMed

Plasmodium falciparum Sir2A (PfSir2A), a member of the sirtuin family of nicotinamide adenine dinucleotide-dependent deacetylases, has been shown to regulate the expression of surface antigens to evade the detection by host immune surveillance. It is thought that PfSir2A achieves this by deacetylating histones. However, the deacetylase activity of PfSir2A is weak. Here we present enzymology and structural evidence supporting that PfSir2A catalyzes the hydrolysis of medium and long chain fatty acyl groups from lysine residues more efficiently. Furthermore, P. falciparum proteins are found to contain such fatty acyl lysine modifications that can be removed by purified PfSir2A in vitro. Together, the data suggest that the physiological function of PfSir2A in antigen variation may be achieved by removing medium and long chain fatty acyl groups from protein lysine residues. The robust activity of PfSir2A would also facilitate the development of PfSir2A inhibitors, which may have therapeutic value in malaria treatment.

Plasmodium falciparum Sir2A Preferentially Hydrolyzes Medium and Long Chain Fatty Acyl Lysine.,Zhu AY, Zhou Y, Khan S, Deitsch KW, Hao Q, Lin H ACS Chem Biol. 2011 Oct 21. PMID:21992006^[9]

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

References

↑ Freitas-Junior LH, Hernandez-Rivas R, Ralph SA, Montiel-Condado D, Ruvalcaba-Salazar OK, Rojas-Meza AP, Mancio-Silva L, Leal-Silvestre RJ, Gontijo AM, Shorte S, Scherf A. Telomeric heterochromatin propagation and histone acetylation control mutually exclusive expression of antigenic variation genes in malaria parasites. Cell. 2005 Apr 8;121(1):25-36. PMID:15820676 doi:10.1016/j.cell.2005.01.037
↑ Merrick CJ, Duraisingh MT. Plasmodium falciparum Sir2: an unusual sirtuin with dual histone deacetylase and ADP-ribosyltransferase activity. Eukaryot Cell. 2007 Nov;6(11):2081-91. Epub 2007 Sep 7. PMID:17827348 doi:10.1128/EC.00114-07
↑ Chakrabarty SP, Saikumari YK, Bopanna MP, Balaram H. Biochemical characterization of Plasmodium falciparum Sir2, a NAD+-dependent deacetylase. Mol Biochem Parasitol. 2008 Apr;158(2):139-51. doi:, 10.1016/j.molbiopara.2007.12.003. Epub 2007 Dec 15. PMID:18221799 doi:10.1016/j.molbiopara.2007.12.003
↑ Prusty D, Mehra P, Srivastava S, Shivange AV, Gupta A, Roy N, Dhar SK. Nicotinamide inhibits Plasmodium falciparum Sir2 activity in vitro and parasite growth. FEMS Microbiol Lett. 2008 May;282(2):266-72. doi:, 10.1111/j.1574-6968.2008.01135.x. Epub 2008 Apr 2. PMID:18397290 doi:10.1111/j.1574-6968.2008.01135.x
↑ Mancio-Silva L, Rojas-Meza AP, Vargas M, Scherf A, Hernandez-Rivas R. Differential association of Orc1 and Sir2 proteins to telomeric domains in Plasmodium falciparum. J Cell Sci. 2008 Jun 15;121(Pt 12):2046-53. doi: 10.1242/jcs.026427. PMID:18525026 doi:10.1242/jcs.026427
↑ French JB, Cen Y, Sauve AA. Plasmodium falciparum Sir2 is an NAD+-dependent deacetylase and an acetyllysine-dependent and acetyllysine-independent NAD+ glycohydrolase. Biochemistry. 2008 Sep 23;47(38):10227-39. doi: 10.1021/bi800767t. Epub 2008 Aug , 26. PMID:18729382 doi:10.1021/bi800767t
↑ Tonkin CJ, Carret CK, Duraisingh MT, Voss TS, Ralph SA, Hommel M, Duffy MF, Silva LM, Scherf A, Ivens A, Speed TP, Beeson JG, Cowman AF. Sir2 paralogues cooperate to regulate virulence genes and antigenic variation in Plasmodium falciparum. PLoS Biol. 2009 Apr 14;7(4):e84. doi: 10.1371/journal.pbio.1000084. PMID:19402747 doi:10.1371/journal.pbio.1000084
↑ Chakrabarty SP, Balaram H. Reversible binding of zinc in Plasmodium falciparum Sir2: structure and activity of the apoenzyme. Biochim Biophys Acta. 2010 Sep;1804(9):1743-50. doi:, 10.1016/j.bbapap.2010.06.010. Epub 2010 Jun 23. PMID:20601220 doi:10.1016/j.bbapap.2010.06.010
↑ Zhu AY, Zhou Y, Khan S, Deitsch KW, Hao Q, Lin H. Plasmodium falciparum Sir2A Preferentially Hydrolyzes Medium and Long Chain Fatty Acyl Lysine. ACS Chem Biol. 2011 Oct 21. PMID:21992006 doi:10.1021/cb200230x

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

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/3u3d"

@@ Line 1: / Line 1: @@
 ==Plasmodium falciparum Sir2A preferentially hydrolyzes medium and long chain fatty acyl lysine==
-<StructureSection load='3u3d' size='340' side='right' caption='[[3u3d]], [[Resolution|resolution]] 2.40&Aring;' scene=''>
+<StructureSection load='3u3d' size='340' side='right'caption='[[3u3d]], [[Resolution|resolution]] 2.40&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[3u3d]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Plaf7 Plaf7]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3U3D OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3U3D FirstGlance]. <br>
+<table><tr><td colspan='2'>[[3u3d]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Plaf7 Plaf7]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3U3D OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3U3D FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
+</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
 <tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=MYK:N~6~-TETRADECANOYL-L-LYSINE'>MYK</scene></td></tr>
-<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3u31|3u31]]</td></tr>
+<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[3u31|3u31]]</div></td></tr>
-<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">PF13_0152, Sir2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=36329 PLAF7])</td></tr>
+<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">PF13_0152, Sir2 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=36329 PLAF7])</td></tr>
-<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Acyl-lysine_deacylase Acyl-lysine deacylase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.5.1.17 3.5.1.17] </span></td></tr>
+<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Acyl-lysine_deacylase Acyl-lysine deacylase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.5.1.17 3.5.1.17] </span></td></tr>
-<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=3u3d FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3u3d OCA], [http://pdbe.org/3u3d PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3u3d RCSB], [http://www.ebi.ac.uk/pdbsum/3u3d PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3u3d ProSAT]</span></td></tr>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3u3d FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3u3d OCA], [https://pdbe.org/3u3d PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3u3d RCSB], [https://www.ebi.ac.uk/pdbsum/3u3d PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3u3d ProSAT]</span></td></tr>
 </table>
 == Function ==
-[[http://www.uniprot.org/uniprot/SIR5_PLAF7 SIR5_PLAF7]] NAD-dependent protein deacylase. Catalyzes the NAD-dependent hydrolysis of medium and long chain fatty acyl groups from lysine residues. Has weak NAD-dependent protein deacetylase activity; however this activity may not be physiologically relevant in vivo. Regulates the expression of the surface antigen-coding var genes central to the malaria pathogenesis. Cooperates with Sir2B to mediate silencing and mutual exclusive expression of only 1 of the 60 subtelomeric var genes at a time, coding for functionally different but epitopically variant versions of the erythrocyte membrane protein 1 (PfEMP1) molecule, to evade the detection by host immune surveillance. Can ADP-ribosylate both histones and itself. May also have a role in telomeric end protection.<ref>PMID:15820676</ref> <ref>PMID:17827348</ref> <ref>PMID:18221799</ref> <ref>PMID:18397290</ref> <ref>PMID:18525026</ref> <ref>PMID:18729382</ref> <ref>PMID:19402747</ref> <ref>PMID:20601220</ref>
+[[https://www.uniprot.org/uniprot/SIR5_PLAF7 SIR5_PLAF7]] NAD-dependent protein deacylase. Catalyzes the NAD-dependent hydrolysis of medium and long chain fatty acyl groups from lysine residues. Has weak NAD-dependent protein deacetylase activity; however this activity may not be physiologically relevant in vivo. Regulates the expression of the surface antigen-coding var genes central to the malaria pathogenesis. Cooperates with Sir2B to mediate silencing and mutual exclusive expression of only 1 of the 60 subtelomeric var genes at a time, coding for functionally different but epitopically variant versions of the erythrocyte membrane protein 1 (PfEMP1) molecule, to evade the detection by host immune surveillance. Can ADP-ribosylate both histones and itself. May also have a role in telomeric end protection.<ref>PMID:15820676</ref> <ref>PMID:17827348</ref> <ref>PMID:18221799</ref> <ref>PMID:18397290</ref> <ref>PMID:18525026</ref> <ref>PMID:18729382</ref> <ref>PMID:19402747</ref> <ref>PMID:20601220</ref>
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==
@@ Line 27: / Line 27: @@
 </StructureSection>
 [[Category: Acyl-lysine deacylase]]
+[[Category: Large Structures]]
 [[Category: Plaf7]]
 [[Category: Hao, Q]]

3u3d

From Proteopedia

Revision as of 05:55, 13 July 2022

Plasmodium falciparum Sir2A preferentially hydrolyzes medium and long chain fatty acyl lysine

Structural highlights

Function

Publication Abstract from PubMed

References

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