2lfa
From Proteopedia
(Difference between revisions)
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<StructureSection load='2lfa' size='340' side='right' caption='[[2lfa]], [[NMR_Ensembles_of_Models | 1 NMR models]]' scene=''> | <StructureSection load='2lfa' size='340' side='right' caption='[[2lfa]], [[NMR_Ensembles_of_Models | 1 NMR models]]' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
| - | [[2lfa]] is a 2 chain structure. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2LFA OCA]. <br> | + | <table><tr><td colspan='2'>[[2lfa]] is a 2 chain structure. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2LFA OCA]. <br> |
| - | <b>[[Non-Standard_Residue|NonStd Res:]]</b> <scene name='pdbligand=2LF:(6S,7S,8S,10R)-2-AMINO-8-HYDROXY-4-OXO-3,6,7,8,9,10-HEXAHYDRO-4H-7,10-EPOXYAZEPINO[1,2-E]PURIN-6-YL+DIHYDROGEN+PHOSPHATE'>2LF</scene>< | + | </td></tr><tr><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=2LF:(6S,7S,8S,10R)-2-AMINO-8-HYDROXY-4-OXO-3,6,7,8,9,10-HEXAHYDRO-4H-7,10-EPOXYAZEPINO[1,2-E]PURIN-6-YL+DIHYDROGEN+PHOSPHATE'>2LF</scene></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=2lfa FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2lfa OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2lfa RCSB], [http://www.ebi.ac.uk/pdbsum/2lfa 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=2lfa FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2lfa OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2lfa RCSB], [http://www.ebi.ac.uk/pdbsum/2lfa PDBsum]</span></td></tr> |
| + | <table> | ||
| + | <div style="background-color:#fffaf0;"> | ||
== Publication Abstract from PubMed == | == Publication Abstract from PubMed == | ||
Diastereomeric 8,5'-cyclopurine 2'-deoxynucleosides, containing a covalent bond between the deoxyribose and the purine base, represent an important class of DNA damage induced by ionizing radiation. The 8,5'-cyclo-2'-deoxyguanosine lesion (cdG) has been recently reported to be a strong block of replication and highly mutagenic in Escherichia coli. The 8,5'-cyclopurine-2'-deoxyriboses are suspected to play a role in the etiology of neurodegeneration in xeroderma pigmentosum patients. These lesions cannot be repaired by base excision repair, but they are substrates for nucleotide excision repair. The structure of an oligodeoxynucleotide duplex containing a site-specific S-cdG lesion placed opposite dC in the complementary strand was obtained by molecular dynamics calculations restrained by distance and dihedral angle restraints obtained from NMR spectroscopy. The S-cdG deoxyribose exhibited the O4'-exo (west) pseudorotation. Significant perturbations were observed for the beta, gamma, and chi torsion angles of the S-cdG nucleoside. Watson-Crick base pairing was conserved at the S-cdG.dC pair. However, the O4'-exo pseudorotation of the S-cdG deoxyribose perturbed the helical twist and base pair stacking at the lesion site and the 5'-neighbor dC.dG base pair. Thermodynamic destabilization of the duplex measured by UV melting experiments correlated with base stacking and structural perturbations involving the modified S-cdG.dC and 3'- neighbor dT.dA base pairs. These perturbations may be responsible for both the genotoxicity of this lesion and its ability to be recognized by nucleotide excision repair. | Diastereomeric 8,5'-cyclopurine 2'-deoxynucleosides, containing a covalent bond between the deoxyribose and the purine base, represent an important class of DNA damage induced by ionizing radiation. The 8,5'-cyclo-2'-deoxyguanosine lesion (cdG) has been recently reported to be a strong block of replication and highly mutagenic in Escherichia coli. The 8,5'-cyclopurine-2'-deoxyriboses are suspected to play a role in the etiology of neurodegeneration in xeroderma pigmentosum patients. These lesions cannot be repaired by base excision repair, but they are substrates for nucleotide excision repair. The structure of an oligodeoxynucleotide duplex containing a site-specific S-cdG lesion placed opposite dC in the complementary strand was obtained by molecular dynamics calculations restrained by distance and dihedral angle restraints obtained from NMR spectroscopy. The S-cdG deoxyribose exhibited the O4'-exo (west) pseudorotation. Significant perturbations were observed for the beta, gamma, and chi torsion angles of the S-cdG nucleoside. Watson-Crick base pairing was conserved at the S-cdG.dC pair. However, the O4'-exo pseudorotation of the S-cdG deoxyribose perturbed the helical twist and base pair stacking at the lesion site and the 5'-neighbor dC.dG base pair. Thermodynamic destabilization of the duplex measured by UV melting experiments correlated with base stacking and structural perturbations involving the modified S-cdG.dC and 3'- neighbor dT.dA base pairs. These perturbations may be responsible for both the genotoxicity of this lesion and its ability to be recognized by nucleotide excision repair. | ||
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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 09:48, 1 May 2014
Oligonucleotide duplex contaning (5'S)-8,5'-cyclo-2'-deoxyguansine
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