1pm5: Difference between revisions

From Proteopedia
Jump to navigation Jump to search
No edit summary
No edit summary
 
(5 intermediate revisions by the same user not shown)
Line 1: Line 1:
[[Image:1pm5.png|left|200px]]


{{STRUCTURE_1pm5| PDB=1pm5 | SCENE= }}
==Crystal structure of wild type Lactococcus lactis Fpg complexed to a tetrahydrofuran containing DNA==
<StructureSection load='1pm5' size='340' side='right'caption='[[1pm5]], [[Resolution|resolution]] 1.95&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[1pm5]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Lactococcus_cremoris Lactococcus cremoris]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1PM5 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1PM5 FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.95&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=3DR:1,2-DIDEOXYRIBOFURANOSE-5-PHOSPHATE'>3DR</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></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=1pm5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1pm5 OCA], [https://pdbe.org/1pm5 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1pm5 RCSB], [https://www.ebi.ac.uk/pdbsum/1pm5 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1pm5 ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/FPG_LACLC FPG_LACLC] Involved in base excision repair of DNA damaged by oxidation or by mutagenic agents. Acts as DNA glycosylase that recognizes and removes damaged bases. Has a preference for oxidized purines, such as 7,8-dihydro-8-oxoguanine (8-oxoG). Has AP (apurinic/apyrimidinic) lyase activity and introduces nicks in the DNA strand. Cleaves the DNA backbone by beta-delta elimination to generate a single-strand break at the site of the removed base with both 3'- and 5'-phosphates.<ref>PMID:7704272</ref>
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
Check<jmol>
  <jmolCheckbox>
    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/pm/1pm5_consurf.spt"</scriptWhenChecked>
    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
    <text>to colour the structure by Evolutionary Conservation</text>
  </jmolCheckbox>
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=1pm5 ConSurf].
<div style="clear:both"></div>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Fpg is a DNA glycosylase that recognizes and excises the mutagenic 8-oxoguanine (8-oxoG) and the potentially lethal formamidopyrimidic residues (Fapy). Fpg is also associated with an AP lyase activity which successively cleaves the abasic (AP) site at the 3' and 5' sides by betadelta-elimination. Here, we present the high-resolution crystal structures of the wild-type and the P1G defective mutant of Fpg from Lactococcus lactis bound to 14mer DNA duplexes containing either a tetrahydrofuran (THF) or 1,3-propanediol (Pr) AP site analogues. Structures show that THF is less extrahelical than Pr and its backbone C5'-C4'-C3' diverges significantly from those of Pr, rAP, 8-oxodG and FapydG. Clearly, the heterocyclic oxygen of THF is pushed back by the carboxylate of the strictly conserved E2 residue. We can propose that the ring-opened form of the damaged deoxyribose is the structure active form of the sugar for Fpg catalysis process. Both structural and functional data suggest that the first step of catalysis mediated by Fpg involves the expulsion of the O4' leaving group facilitated by general acid catalysis (involving E2), rather than the immediate cleavage of the N-glycosic bond of the damaged nucleoside.


===Crystal structure of wild type Lactococcus lactis Fpg complexed to a tetrahydrofuran containing DNA===
Structural insights into abasic site for Fpg specific binding and catalysis: comparative high-resolution crystallographic studies of Fpg bound to various models of abasic site analogues-containing DNA.,Pereira de Jesus K, Serre L, Zelwer C, Castaing B Nucleic Acids Res. 2005 Oct 20;33(18):5936-44. Print 2005. PMID:16243784<ref>PMID:16243784</ref>


{{ABSTRACT_PUBMED_16243784}}
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 
</div>
==About this Structure==
<div class="pdbe-citations 1pm5" style="background-color:#fffaf0;"></div>
[[1pm5]] is a 3 chain structure with sequence from [http://en.wikipedia.org/wiki/Lactococcus_lactis_subsp._cremoris Lactococcus lactis subsp. cremoris]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1PM5 OCA].


==See Also==
==See Also==
*[[DNA glycosylate|DNA glycosylate]]
*[[DNA glycosylase 3D structures|DNA glycosylase 3D structures]]
 
== References ==
==Reference==
<references/>
<ref group="xtra">PMID:016243784</ref><references group="xtra"/>
__TOC__
[[Category: DNA-formamidopyrimidine glycosylase]]
</StructureSection>
[[Category: Lactococcus lactis subsp. cremoris]]
[[Category: Lactococcus cremoris]]
[[Category: Castaing, B.]]
[[Category: Large Structures]]
[[Category: Jesus-Tran, K Pereira de.]]
[[Category: Castaing B]]
[[Category: Serre, L.]]
[[Category: Pereira de Jesus-Tran K]]
[[Category: Zelwer, C.]]
[[Category: Serre L]]
[[Category: Abasic site]]
[[Category: Zelwer C]]
[[Category: Dna repair]]
[[Category: Fpg]]
[[Category: Hydrolase-dna complex]]
[[Category: Mutm]]

Latest revision as of 12:45, 16 August 2023

Crystal structure of wild type Lactococcus lactis Fpg complexed to a tetrahydrofuran containing DNACrystal structure of wild type Lactococcus lactis Fpg complexed to a tetrahydrofuran containing DNA

Structural highlights

1pm5 is a 3 chain structure with sequence from Lactococcus cremoris. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 1.95Å
Ligands:, ,
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

FPG_LACLC Involved in base excision repair of DNA damaged by oxidation or by mutagenic agents. Acts as DNA glycosylase that recognizes and removes damaged bases. Has a preference for oxidized purines, such as 7,8-dihydro-8-oxoguanine (8-oxoG). Has AP (apurinic/apyrimidinic) lyase activity and introduces nicks in the DNA strand. Cleaves the DNA backbone by beta-delta elimination to generate a single-strand break at the site of the removed base with both 3'- and 5'-phosphates.[1]

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

Fpg is a DNA glycosylase that recognizes and excises the mutagenic 8-oxoguanine (8-oxoG) and the potentially lethal formamidopyrimidic residues (Fapy). Fpg is also associated with an AP lyase activity which successively cleaves the abasic (AP) site at the 3' and 5' sides by betadelta-elimination. Here, we present the high-resolution crystal structures of the wild-type and the P1G defective mutant of Fpg from Lactococcus lactis bound to 14mer DNA duplexes containing either a tetrahydrofuran (THF) or 1,3-propanediol (Pr) AP site analogues. Structures show that THF is less extrahelical than Pr and its backbone C5'-C4'-C3' diverges significantly from those of Pr, rAP, 8-oxodG and FapydG. Clearly, the heterocyclic oxygen of THF is pushed back by the carboxylate of the strictly conserved E2 residue. We can propose that the ring-opened form of the damaged deoxyribose is the structure active form of the sugar for Fpg catalysis process. Both structural and functional data suggest that the first step of catalysis mediated by Fpg involves the expulsion of the O4' leaving group facilitated by general acid catalysis (involving E2), rather than the immediate cleavage of the N-glycosic bond of the damaged nucleoside.

Structural insights into abasic site for Fpg specific binding and catalysis: comparative high-resolution crystallographic studies of Fpg bound to various models of abasic site analogues-containing DNA.,Pereira de Jesus K, Serre L, Zelwer C, Castaing B Nucleic Acids Res. 2005 Oct 20;33(18):5936-44. Print 2005. PMID:16243784[2]

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

See Also

References

  1. Duwat P, de Oliveira R, Ehrlich SD, Boiteux S. Repair of oxidative DNA damage in gram-positive bacteria: the Lactococcus lactis Fpg protein. Microbiology. 1995 Feb;141 ( Pt 2):411-7. PMID:7704272
  2. Pereira de Jesus K, Serre L, Zelwer C, Castaing B. Structural insights into abasic site for Fpg specific binding and catalysis: comparative high-resolution crystallographic studies of Fpg bound to various models of abasic site analogues-containing DNA. Nucleic Acids Res. 2005 Oct 20;33(18):5936-44. Print 2005. PMID:16243784 doi:http://dx.doi.org/33/18/5936

1pm5, resolution 1.95Å

Drag the structure with the mouse to rotate

Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)

OCA