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| - | [[Image:289d.gif|left|200px]] | |
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| - | {{Structure
| + | ==TARGETING THE MINOR GROOVE OF DNA: CRYSTAL STRUCTURES OF TWO COMPLEXES BETWEEN FURAN DERIVATIVES OF BERENIL AND THE DNA DODECAMER D(CGCGAATTCGCG)2== |
| - | |PDB= 289d |SIZE=350|CAPTION= <scene name='initialview01'>289d</scene>, resolution 2.200Å
| + | <StructureSection load='289d' size='340' side='right'caption='[[289d]], [[Resolution|resolution]] 2.20Å' scene=''> |
| - | |SITE=
| + | == Structural highlights == |
| - | |LIGAND= <scene name='pdbligand=D19:2,5-BIS{[4-(N-CYCLOPROPYLDIAMINOMETHYL)PHENYL]}FURAN'>D19</scene>, <scene name='pdbligand=DA:2'-DEOXYADENOSINE-5'-MONOPHOSPHATE'>DA</scene>, <scene name='pdbligand=DC:2'-DEOXYCYTIDINE-5'-MONOPHOSPHATE'>DC</scene>, <scene name='pdbligand=DG:2'-DEOXYGUANOSINE-5'-MONOPHOSPHATE'>DG</scene>, <scene name='pdbligand=DT:THYMIDINE-5'-MONOPHOSPHATE'>DT</scene> | + | <table><tr><td colspan='2'>[[289d]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=289D OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=289D FirstGlance]. <br> |
| - | |ACTIVITY=
| + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.2Å</td></tr> |
| - | |GENE=
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=D19:2,5-BIS{[4-(N-CYCLOPROPYLDIAMINOMETHYL)PHENYL]}FURAN'>D19</scene></td></tr> |
| - | |DOMAIN=
| + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=289d FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=289d OCA], [https://pdbe.org/289d PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=289d RCSB], [https://www.ebi.ac.uk/pdbsum/289d PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=289d ProSAT]</span></td></tr> |
| - | |RELATEDENTRY=
| + | </table> |
| - | |RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=289d FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=289d OCA], [http://www.ebi.ac.uk/pdbsum/289d PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=289d RCSB]</span>
| + | __TOC__ |
| - | }}
| + | </StructureSection> |
| - | | + | [[Category: Large Structures]] |
| - | '''TARGETING THE MINOR GROOVE OF DNA: CRYSTAL STRUCTURES OF TWO COMPLEXES BETWEEN FURAN DERIVATIVES OF BERENIL AND THE DNA DODECAMER D(CGCGAATTCGCG)2'''
| + | [[Category: Blagburn BL]] |
| - | | + | [[Category: Boykin DW]] |
| - | | + | [[Category: Clark GR]] |
| - | ==Overview==
| + | [[Category: Hall JE]] |
| - | Crystal structures are reported of complexes of two novel furan derivatives of berenil with alkyl benzamidine groups bound to the DNA sequence d(CGCGAATTCGCG)2. They have both been determined to 2.2 A resolution and refined to R factors of 16.9% and 18.6%. In both structures the alkyl substituents, cyclopropyl and isopropyl, are found to be orientated away from the floor of the minor groove. The drugs are located in the minor groove by two strong amidinium hydrogen bonds, to the O2 of the thymines situated at the 5' and 3' ends of the AT-rich region. The isopropyl-substituted derivative has a tight hydrogen-bonded water network in the minor groove at one amidine site, which alters the orientation of the isopropyl substituent. This compound has superior DNA-binding properties and activity against Pneumocystis carinii and Cryptosporidium parvum infections in vivo compared to the cyclopropyl derivative, which in turn is superior to the parent furan compound. We suggest that the nature and extent of the interactions of these compounds in the DNA minor groove play an important role in these activities, possibly in conjunction with a DNA-binding protein. The overall effect of these alkyl benzamidine substitutions is to increase the binding of the drugs to the minor groove.
| + | [[Category: Kumar A]] |
| - | | + | [[Category: Neidle S]] |
| - | ==About this Structure==
| + | [[Category: Tidwell RR]] |
| - | 289D is a [[Protein complex]] structure of sequences from [http://en.wikipedia.org/wiki/ ]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=289D OCA].
| + | [[Category: Trent JO]] |
| - | | + | [[Category: Wilson WD]] |
| - | ==Reference==
| + | |
| - | Targeting the minor groove of DNA: crystal structures of two complexes between furan derivatives of berenil and the DNA dodecamer d(CGCGAATTCGCG)2., Trent JO, Clark GR, Kumar A, Wilson WD, Boykin DW, Hall JE, Tidwell RR, Blagburn BL, Neidle S, J Med Chem. 1996 Nov 8;39(23):4554-62. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/8917643 8917643]
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| - | [[Category: Protein complex]] | + | |
| - | [[Category: Blagburn, B L.]] | + | |
| - | [[Category: Boykin, D W.]] | + | |
| - | [[Category: Clark, G R.]] | + | |
| - | [[Category: Hall, J E.]] | + | |
| - | [[Category: Kumar, A.]] | + | |
| - | [[Category: Neidle, S.]] | + | |
| - | [[Category: Tidwell, R R.]] | + | |
| - | [[Category: Trent, J O.]] | + | |
| - | [[Category: Wilson, W D.]] | + | |
| - | [[Category: b-dna]]
| + | |
| - | [[Category: complexed with drug]]
| + | |
| - | [[Category: double helix]]
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| - | | + | |
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 01:45:53 2008''
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