2l46
From Proteopedia
(Difference between revisions)
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<StructureSection load='2l46' size='340' side='right' caption='[[2l46]], [[NMR_Ensembles_of_Models | 20 NMR models]]' scene=''> | <StructureSection load='2l46' size='340' side='right' caption='[[2l46]], [[NMR_Ensembles_of_Models | 20 NMR models]]' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
| - | [[2l46]] is a 2 chain structure. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2L46 OCA]. <br> | + | <table><tr><td colspan='2'>[[2l46]] is a 2 chain structure. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2L46 OCA]. <br> |
| - | <b>[[Ligand|Ligands:]]</b> <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene><br> | + | </td></tr><tr><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ZN:ZINC+ION'>ZN</scene><br> |
| - | <b>[[Related_structure|Related:]]</b> [[2l44|2l44]], [[2l45|2l45]]< | + | <tr><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2l44|2l44]], [[2l45|2l45]]</td></tr> |
| - | <b>Activity:</b> <span class='plainlinks'>[http://en.wikipedia.org/wiki/Glucokinase Glucokinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.1.2 2.7.1.2] </span>< | + | <tr><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Glucokinase Glucokinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.1.2 2.7.1.2] </span></td></tr> |
| - | <b>Resources:</b> <span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2l46 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2l46 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2l46 RCSB], [http://www.ebi.ac.uk/pdbsum/2l46 PDBsum]</span>< | + | <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=2l46 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2l46 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2l46 RCSB], [http://www.ebi.ac.uk/pdbsum/2l46 PDBsum]</span></td></tr> |
| + | <table> | ||
| + | <div style="background-color:#fffaf0;"> | ||
== Publication Abstract from PubMed == | == Publication Abstract from PubMed == | ||
This paper describes for the first time the intimate molecular details of the association between a platinated oligonucleotide and a zinc finger peptide. Site-specific platination of the guanine in a single-stranded hexanucleotide gave {[Pt(dien)d(5'-TACGCC-3')], Pt(dien)(6-mer)} (II) characterized by mass spectrometry and (1)H nuclear magnetic resonance (NMR) spectroscopy. The work extends the study of platinum-nucleobase complex-zinc finger interactions using small molecules such as [Pt(dien)(9-EtGua)](2+) (I). The structure of the (34-52) C-terminal finger of HIV nucleocapsid protein HIVNCp7 (ZF1) was characterized by (1)H NMR spectroscopy and compared with that of the N-terminal single finger and the two-finger "intact" NCp7. Interaction of II with ZF1 results in significant changes in comparison to the "free" uncomplexed hexanucleotide; the major changes occurring for Trp37 resonances that are broadened and moved upfield, and other major shifts are for Gln45 (Hepsilon21, Hgamma3, Qbeta), Met46 (NH, Hgamma2), Lys47 (NH, Qgamma), and Glu50 (Hgamma2, Hgamma3). The Zn-Cys/His chemical shifts show only marginal deviations. The solution structures of ZF1 and the 6-mer-ZF1 and II-ZF1 adducts were calculated from the nuclear Overhauser effect spectroscopy-derived distance constraints. The DNA position in the II-ZF1 adduct is completely different than in the absence of platinum. Major differences are the appearance of new Met46-Cyt6 H5 and Trp37-Cyt5 H5 contacts but severe weakening of the Trp37-Gua4 contact, attributed to the steric effects caused by Gua4 platination, accompanied by a change in the position of the aromatic ring. The results demonstrate the feasibility of targeting specific ZF motifs with DNA-tethered coordination compounds, such as Pt compounds and Co macrocycles, with implications for drug targetting and indeed the intimate mechanisms of DNA repair of platinated DNA. | This paper describes for the first time the intimate molecular details of the association between a platinated oligonucleotide and a zinc finger peptide. Site-specific platination of the guanine in a single-stranded hexanucleotide gave {[Pt(dien)d(5'-TACGCC-3')], Pt(dien)(6-mer)} (II) characterized by mass spectrometry and (1)H nuclear magnetic resonance (NMR) spectroscopy. The work extends the study of platinum-nucleobase complex-zinc finger interactions using small molecules such as [Pt(dien)(9-EtGua)](2+) (I). The structure of the (34-52) C-terminal finger of HIV nucleocapsid protein HIVNCp7 (ZF1) was characterized by (1)H NMR spectroscopy and compared with that of the N-terminal single finger and the two-finger "intact" NCp7. Interaction of II with ZF1 results in significant changes in comparison to the "free" uncomplexed hexanucleotide; the major changes occurring for Trp37 resonances that are broadened and moved upfield, and other major shifts are for Gln45 (Hepsilon21, Hgamma3, Qbeta), Met46 (NH, Hgamma2), Lys47 (NH, Qgamma), and Glu50 (Hgamma2, Hgamma3). The Zn-Cys/His chemical shifts show only marginal deviations. The solution structures of ZF1 and the 6-mer-ZF1 and II-ZF1 adducts were calculated from the nuclear Overhauser effect spectroscopy-derived distance constraints. The DNA position in the II-ZF1 adduct is completely different than in the absence of platinum. Major differences are the appearance of new Met46-Cyt6 H5 and Trp37-Cyt5 H5 contacts but severe weakening of the Trp37-Gua4 contact, attributed to the steric effects caused by Gua4 platination, accompanied by a change in the position of the aromatic ring. The results demonstrate the feasibility of targeting specific ZF motifs with DNA-tethered coordination compounds, such as Pt compounds and Co macrocycles, with implications for drug targetting and indeed the intimate mechanisms of DNA repair of platinated DNA. | ||
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
== References == | == References == | ||
<references/> | <references/> | ||
Revision as of 09:39, 1 May 2014
C-terminal zinc finger of the HIVNCp7 with platinated DNA
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Categories: Cabrita, E. | Erhardt, S. | Farrell, N. | Quintal, S. | Viegas, A. | Hiv | Ncp7 | Platinum | Viral protein-dna complex
