3rzh: Difference between revisions

Revision as of 10:31, 22 June 2022

Duplex Interrogation by a Direct DNA Repair Protein in the Search of Damage

Structural highlights

3rzh is a 3 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	XL3
NonStd Res:	ME6
Related:	3rzg, 3rzj, 3rzk, 3rzl, 3rzm
Gene:	ALKBH2, ABH2 (HUMAN)
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[ALKB2_HUMAN] Dioxygenase that repairs alkylated DNA and RNA containing 1-methyladenine and 3-methylcytosine by oxidative demethylation. Can also repair alkylated DNA containing 1-ethenoadenine (in vitro). Has strong preference for double-stranded DNA. Has low efficiency with single-stranded substrates. Requires molecular oxygen, alpha-ketoglutarate and iron.^[1] ^[2] ^[3] ^[4] ^[5]

Publication Abstract from PubMed

ALKBH2 is a direct DNA repair dioxygenase guarding the mammalian genome against N(1)-methyladenine, N(3)-methylcytosine and 1,N(6)-ethenoadenine damage. A prerequisite for repair is to identify these lesions in the genome. Here we present crystal structures of human ALKBH2 bound to different duplex DNAs. Together with computational and biochemical analyses, our results suggest that DNA interrogation by ALKBH2 has two previously unknown features: (i) ALKBH2 probes base-pair stability and detects base pairs with reduced stability, and (ii) ALKBH2 does not have nor need a damage-checking site, which is critical for preventing spurious base cleavage for several glycosylases. The demethylation mechanism of ALKBH2 insures that only cognate lesions are oxidized and reversed to normal bases, and that a flipped, non-substrate base remains intact in the active site. Overall, the combination of duplex interrogation and oxidation chemistry allows ALKBH2 to detect and process diverse lesions efficiently and correctly.

Duplex interrogation by a direct DNA repair protein in search of base damage.,Yi C, Chen B, Qi B, Zhang W, Jia G, Zhang L, Li CJ, Dinner AR, Yang CG, He C Nat Struct Mol Biol. 2012 Jun 3;19(7):671-6. doi: 10.1038/nsmb.2320. PMID:22659876^[6]

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

References

↑ Duncan T, Trewick SC, Koivisto P, Bates PA, Lindahl T, Sedgwick B. Reversal of DNA alkylation damage by two human dioxygenases. Proc Natl Acad Sci U S A. 2002 Dec 24;99(26):16660-5. Epub 2002 Dec 16. PMID:12486230 doi:10.1073/pnas.262589799
↑ Aas PA, Otterlei M, Falnes PO, Vagbo CB, Skorpen F, Akbari M, Sundheim O, Bjoras M, Slupphaug G, Seeberg E, Krokan HE. Human and bacterial oxidative demethylases repair alkylation damage in both RNA and DNA. Nature. 2003 Feb 20;421(6925):859-63. PMID:12594517 doi:10.1038/nature01363
↑ Lee DH, Jin SG, Cai S, Chen Y, Pfeifer GP, O'Connor TR. Repair of methylation damage in DNA and RNA by mammalian AlkB homologues. J Biol Chem. 2005 Nov 25;280(47):39448-59. Epub 2005 Sep 20. PMID:16174769 doi:M509881200
↑ Ringvoll J, Moen MN, Nordstrand LM, Meira LB, Pang B, Bekkelund A, Dedon PC, Bjelland S, Samson LD, Falnes PO, Klungland A. AlkB homologue 2-mediated repair of ethenoadenine lesions in mammalian DNA. Cancer Res. 2008 Jun 1;68(11):4142-9. doi: 10.1158/0008-5472.CAN-08-0796. PMID:18519673 doi:https://dx.doi.org/10.1158/0008-5472.CAN-08-0796
↑ Yang CG, Yi C, Duguid EM, Sullivan CT, Jian X, Rice PA, He C. Crystal structures of DNA/RNA repair enzymes AlkB and ABH2 bound to dsDNA. Nature. 2008 Apr 24;452(7190):961-5. PMID:18432238 doi:https://dx.doi.org/10.1038/nature06889
↑ Yi C, Chen B, Qi B, Zhang W, Jia G, Zhang L, Li CJ, Dinner AR, Yang CG, He C. Duplex interrogation by a direct DNA repair protein in search of base damage. Nat Struct Mol Biol. 2012 Jun 3;19(7):671-6. doi: 10.1038/nsmb.2320. PMID:22659876 doi:10.1038/nsmb.2320

Proteopedia Page Contributors and Editors (what is this?)

OCA

[1] Duncan T, Trewick SC, Koivisto P, Bates PA, Lindahl T, Sedgwick B. Reversal of DNA alkylation damage by two human dioxygenases. Proc Natl Acad Sci U S A. 2002 Dec 24;99(26):16660-5. Epub 2002 Dec 16. PMID:12486230 doi:10.1073/pnas.262589799

[2] Aas PA, Otterlei M, Falnes PO, Vagbo CB, Skorpen F, Akbari M, Sundheim O, Bjoras M, Slupphaug G, Seeberg E, Krokan HE. Human and bacterial oxidative demethylases repair alkylation damage in both RNA and DNA. Nature. 2003 Feb 20;421(6925):859-63. PMID:12594517 doi:10.1038/nature01363

[3] Lee DH, Jin SG, Cai S, Chen Y, Pfeifer GP, O'Connor TR. Repair of methylation damage in DNA and RNA by mammalian AlkB homologues. J Biol Chem. 2005 Nov 25;280(47):39448-59. Epub 2005 Sep 20. PMID:16174769 doi:M509881200

[4] Ringvoll J, Moen MN, Nordstrand LM, Meira LB, Pang B, Bekkelund A, Dedon PC, Bjelland S, Samson LD, Falnes PO, Klungland A. AlkB homologue 2-mediated repair of ethenoadenine lesions in mammalian DNA. Cancer Res. 2008 Jun 1;68(11):4142-9. doi: 10.1158/0008-5472.CAN-08-0796. PMID:18519673 doi:https://dx.doi.org/10.1158/0008-5472.CAN-08-0796

[5] Yang CG, Yi C, Duguid EM, Sullivan CT, Jian X, Rice PA, He C. Crystal structures of DNA/RNA repair enzymes AlkB and ABH2 bound to dsDNA. Nature. 2008 Apr 24;452(7190):961-5. PMID:18432238 doi:https://dx.doi.org/10.1038/nature06889

[6] Yi C, Chen B, Qi B, Zhang W, Jia G, Zhang L, Li CJ, Dinner AR, Yang CG, He C. Duplex interrogation by a direct DNA repair protein in search of base damage. Nat Struct Mol Biol. 2012 Jun 3;19(7):671-6. doi: 10.1038/nsmb.2320. PMID:22659876 doi:10.1038/nsmb.2320

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[2]

[3]

[4]

[5]

[6]

@@ Line 1: / Line 1: @@
 ==Duplex Interrogation by a Direct DNA Repair Protein in the Search of Damage==
-<StructureSection load='3rzh' size='340' side='right' caption='[[3rzh]], [[Resolution|resolution]] 2.25&Aring;' scene=''>
+<StructureSection load='3rzh' size='340' side='right'caption='[[3rzh]], [[Resolution|resolution]] 2.25&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[3rzh]] is a 3 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3RZH OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3RZH FirstGlance]. <br>
+<table><tr><td colspan='2'>[[3rzh]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3RZH OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3RZH FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=XL3:PROPANE-1-THIOL'>XL3</scene></td></tr>
+</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=XL3:PROPANE-1-THIOL'>XL3</scene></td></tr>
 <tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=ME6:[(2R,3S,5R)-5-(4-AZANYL-3-METHYL-2-OXO-PYRIMIDIN-3-IUM-1-YL)-3-HYDROXY-OXOLAN-2-YL]METHYL+DIHYDROGEN+PHOSPHATE'>ME6</scene></td></tr>
-<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3rzg|3rzg]], [[3rzj|3rzj]], [[3rzk|3rzk]], [[3rzl|3rzl]], [[3rzm|3rzm]]</td></tr>
+<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[3rzg|3rzg]], [[3rzj|3rzj]], [[3rzk|3rzk]], [[3rzl|3rzl]], [[3rzm|3rzm]]</div></td></tr>
-<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">ALKBH2, ABH2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
+<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">ALKBH2, ABH2 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=3rzh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3rzh OCA], [http://pdbe.org/3rzh PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3rzh RCSB], [http://www.ebi.ac.uk/pdbsum/3rzh PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3rzh 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=3rzh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3rzh OCA], [https://pdbe.org/3rzh PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3rzh RCSB], [https://www.ebi.ac.uk/pdbsum/3rzh PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3rzh ProSAT]</span></td></tr>
 </table>
 == Function ==
-[[http://www.uniprot.org/uniprot/ALKB2_HUMAN ALKB2_HUMAN]] Dioxygenase that repairs alkylated DNA and RNA containing 1-methyladenine and 3-methylcytosine by oxidative demethylation. Can also repair alkylated DNA containing 1-ethenoadenine (in vitro). Has strong preference for double-stranded DNA. Has low efficiency with single-stranded substrates. Requires molecular oxygen, alpha-ketoglutarate and iron.<ref>PMID:12486230</ref> <ref>PMID:12594517</ref> <ref>PMID:16174769</ref> <ref>PMID:18519673</ref> <ref>PMID:18432238</ref>
+[[https://www.uniprot.org/uniprot/ALKB2_HUMAN ALKB2_HUMAN]] Dioxygenase that repairs alkylated DNA and RNA containing 1-methyladenine and 3-methylcytosine by oxidative demethylation. Can also repair alkylated DNA containing 1-ethenoadenine (in vitro). Has strong preference for double-stranded DNA. Has low efficiency with single-stranded substrates. Requires molecular oxygen, alpha-ketoglutarate and iron.<ref>PMID:12486230</ref> <ref>PMID:12594517</ref> <ref>PMID:16174769</ref> <ref>PMID:18519673</ref> <ref>PMID:18432238</ref>
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==
@@ Line 23: / Line 23: @@
 ==See Also==
-*[[Dioxygenase|Dioxygenase]]
+*[[Dioxygenase 3D structures|Dioxygenase 3D structures]]
 == References ==
 <references/>
@@ Line 29: / Line 29: @@
 </StructureSection>
 [[Category: Human]]
+[[Category: Large Structures]]
 [[Category: Chen, B]]
 [[Category: Dinner, A]]

3rzh: Difference between revisions

Revision as of 10:31, 22 June 2022

Duplex Interrogation by a Direct DNA Repair Protein in the Search of Damage

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

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