2r2s: Difference between revisions
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[[Image: | ==Co(III)bleomycinB2 bound to d(ATTAGTTATAACTAAT) complexed with MMLV RT catalytic fragment== | ||
<StructureSection load='2r2s' size='340' side='right' caption='[[2r2s]], [[Resolution|resolution]] 2.80Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[2r2s]] is a 3 chain structure with sequence from [http://en.wikipedia.org/wiki/Moloney_murine_leukemia_virus Moloney murine leukemia virus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2R2S OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2R2S FirstGlance]. <br> | |||
</td></tr><tr><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=3CO:COBALT+(III)+ION'>3CO</scene>, <scene name='pdbligand=BLB:BLEOMYCIN+B2'>BLB</scene><br> | |||
<tr><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2r2r|2r2r]], [[2r2t|2r2t]], [[2r2u|2r2u]]</td></tr> | |||
<tr><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">pol ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=11801 Moloney murine leukemia virus])</td></tr> | |||
<tr><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/RNA-directed_DNA_polymerase RNA-directed DNA polymerase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.7.49 2.7.7.49] </span></td></tr> | |||
<tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2r2s FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2r2s OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2r2s RCSB], [http://www.ebi.ac.uk/pdbsum/2r2s PDBsum]</span></td></tr> | |||
<table> | |||
== 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/r2/2r2s_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/chain_selection.php?pdb_ID=2ata ConSurf]. | |||
<div style="clear:both"></div> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Bleomycins constitute a widely studied class of complex DNA cleaving natural products that are used to treat various cancers. Since their first isolation, the bleomycins have provided a paradigm for the development and discovery of additional DNA-cleaving chemotherapeutic agents. The bleomycins consist of a disaccharide-modified metal-binding domain connected to a bithiazole/C-terminal tail via a methylvalerate-Thr linker and induce DNA damage after oxygen activation through site-selective cleavage of duplex DNA at 5'-GT/C sites. Here, we present crystal structures of two different 5'-GT containing oligonucleotides in both the presence and absence of bound Co(III).bleomycin B(2). Several findings from our studies impact the current view of bleomycin binding to DNA. First, we report that the bithiazole intercalates in two distinct modes and can do so independently of well ordered minor groove binding of the metal binding/disaccharide domains. Second, the Co(III)-coordinating equatorial ligands in our structure include the imidazole, histidine amide, pyrimidine N1, and the secondary amine of the beta aminoalanine, whereas the primary amine acts as an axial ligand. Third, minor groove binding of Co(III).bleomycin involves direct hydrogen bonding interactions of the metal binding domain and disaccharide with the DNA. Finally, modeling of a hydroperoxide ligand coordinated to Co(III) suggests that it is ideally positioned for initiation of C4'-H abstraction. | |||
Crystal structure of DNA-bound Co(III) bleomycin B2: Insights on intercalation and minor groove binding.,Goodwin KD, Lewis MA, Long EC, Georgiadis MM Proc Natl Acad Sci U S A. 2008 Apr 1;105(13):5052-6. Epub 2008 Mar 24. PMID:18362349<ref>PMID:18362349</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
==See Also== | ==See Also== | ||
*[[Reverse transcriptase|Reverse transcriptase]] | *[[Reverse transcriptase|Reverse transcriptase]] | ||
== References == | |||
== | <references/> | ||
< | __TOC__ | ||
</StructureSection> | |||
[[Category: Moloney murine leukemia virus]] | [[Category: Moloney murine leukemia virus]] | ||
[[Category: RNA-directed DNA polymerase]] | [[Category: RNA-directed DNA polymerase]] | ||
Revision as of 12:03, 29 September 2014
Co(III)bleomycinB2 bound to d(ATTAGTTATAACTAAT) complexed with MMLV RT catalytic fragmentCo(III)bleomycinB2 bound to d(ATTAGTTATAACTAAT) complexed with MMLV RT catalytic fragment
Structural highlights
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 PubMedBleomycins constitute a widely studied class of complex DNA cleaving natural products that are used to treat various cancers. Since their first isolation, the bleomycins have provided a paradigm for the development and discovery of additional DNA-cleaving chemotherapeutic agents. The bleomycins consist of a disaccharide-modified metal-binding domain connected to a bithiazole/C-terminal tail via a methylvalerate-Thr linker and induce DNA damage after oxygen activation through site-selective cleavage of duplex DNA at 5'-GT/C sites. Here, we present crystal structures of two different 5'-GT containing oligonucleotides in both the presence and absence of bound Co(III).bleomycin B(2). Several findings from our studies impact the current view of bleomycin binding to DNA. First, we report that the bithiazole intercalates in two distinct modes and can do so independently of well ordered minor groove binding of the metal binding/disaccharide domains. Second, the Co(III)-coordinating equatorial ligands in our structure include the imidazole, histidine amide, pyrimidine N1, and the secondary amine of the beta aminoalanine, whereas the primary amine acts as an axial ligand. Third, minor groove binding of Co(III).bleomycin involves direct hydrogen bonding interactions of the metal binding domain and disaccharide with the DNA. Finally, modeling of a hydroperoxide ligand coordinated to Co(III) suggests that it is ideally positioned for initiation of C4'-H abstraction. Crystal structure of DNA-bound Co(III) bleomycin B2: Insights on intercalation and minor groove binding.,Goodwin KD, Lewis MA, Long EC, Georgiadis MM Proc Natl Acad Sci U S A. 2008 Apr 1;105(13):5052-6. Epub 2008 Mar 24. PMID:18362349[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences |
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Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)
OCA- Moloney murine leukemia virus
- RNA-directed DNA polymerase
- Georgiadis, M M.
- Goodwin, K D.
- Lewis, M A.
- Long, E C.
- Bleomycin
- Dna integration
- Dna recombination
- Drug-dna complex
- Endonuclease
- Mmlv rt
- Multifunctional enzyme
- Nuclease
- Nucleotidyltransferase
- Protein-dna complex
- Rna-directed dna polymerase
- Transferase
- Transferase-dna complex