1rn9
From Proteopedia
(New page: 200px<br /><applet load="1rn9" size="450" color="white" frame="true" align="right" spinBox="true" caption="1rn9" /> '''A SHORT LEXITROPSIN THAT RECOGNIZES THE DNA ...) |
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'''A SHORT LEXITROPSIN THAT RECOGNIZES THE DNA MINOR GROOVE AT 5'-ACTAGT-3': UNDERSTANDING THE ROLE OF ISOPROPYL-THIAZOLE'''<br /> | '''A SHORT LEXITROPSIN THAT RECOGNIZES THE DNA MINOR GROOVE AT 5'-ACTAGT-3': UNDERSTANDING THE ROLE OF ISOPROPYL-THIAZOLE'''<br /> | ||
==Overview== | ==Overview== | ||
| - | Isopropyl-thiazole ((iPr)Th) represents a new addition to the building | + | Isopropyl-thiazole ((iPr)Th) represents a new addition to the building blocks of nucleic acid minor groove-binding molecules. The DNA decamer duplex d(CGACTAGTCG)(2) is bound by a short lexitropsin of sequence formyl-PyPy(iPr)Th-Dp (where Py represents N-methyl pyrrole, (iPr)Th represents thiazole with an isopropyl group attached, and Dp represents dimethylaminopropyl). NMR data indicate ligand binding in the minor groove of DNA to the sequence 5'-ACT(5)AG(7)T-3' at a 2:1 ratio of ligand to DNA duplex. Ligand binding, assisted by the enhanced hydrophobicity of the (iPr)Th group, occurs in a head-to-tail fashion, the formyl headgroups being located toward the 5'-ends of the DNA sequence. Sequence reading is augmented through hydrogen bond formation between the exocyclic amine protons of G(7) and the (iPr)Th nitrogen, which lies on the minor groove floor. The B(I)/B(II) DNA backbone equilibrium is altered at the T(5) 3'-phosphate position to accommodate a B(II) configuration. The ligands bind in a staggered mode with respect to one another creating a six base pair DNA reading frame. The introduction of a new DNA sequence-reading element into the recognition jigsaw, combined with an extended reading frame for a small lexitropsin with enhanced hydrophobicity, holds great promise in the development of new, potentially commercially viable drug lead candidates for gene targeting. |
==About this Structure== | ==About this Structure== | ||
| - | 1RN9 is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/ ]. Full crystallographic information is available from [http:// | + | 1RN9 is a [http://en.wikipedia.org/wiki/Protein_complex 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=1RN9 OCA]. |
==Reference== | ==Reference== | ||
Short lexitropsin that recognizes the DNA minor groove at 5'-ACTAGT-3': understanding the role of isopropyl-thiazole., Anthony NG, Johnston BF, Khalaf AI, MacKay SP, Parkinson JA, Suckling CJ, Waigh RD, J Am Chem Soc. 2004 Sep 15;126(36):11338-49. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=15355117 15355117] | Short lexitropsin that recognizes the DNA minor groove at 5'-ACTAGT-3': understanding the role of isopropyl-thiazole., Anthony NG, Johnston BF, Khalaf AI, MacKay SP, Parkinson JA, Suckling CJ, Waigh RD, J Am Chem Soc. 2004 Sep 15;126(36):11338-49. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=15355117 15355117] | ||
[[Category: Protein complex]] | [[Category: Protein complex]] | ||
| - | [[Category: Anthony, N | + | [[Category: Anthony, N G.]] |
| - | [[Category: Johnston, B | + | [[Category: Johnston, B F.]] |
| - | [[Category: Khalaf, A | + | [[Category: Khalaf, A I.]] |
| - | [[Category: Mackay, S | + | [[Category: Mackay, S P.]] |
| - | [[Category: Parkinson, J | + | [[Category: Parkinson, J A.]] |
| - | [[Category: Suckling, C | + | [[Category: Suckling, C J.]] |
| - | [[Category: Waigh, R | + | [[Category: Waigh, R D.]] |
[[Category: dna]] | [[Category: dna]] | ||
[[Category: double helix]] | [[Category: double helix]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 14:52:36 2008'' |
Revision as of 12:52, 21 February 2008
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A SHORT LEXITROPSIN THAT RECOGNIZES THE DNA MINOR GROOVE AT 5'-ACTAGT-3': UNDERSTANDING THE ROLE OF ISOPROPYL-THIAZOLE
Overview
Isopropyl-thiazole ((iPr)Th) represents a new addition to the building blocks of nucleic acid minor groove-binding molecules. The DNA decamer duplex d(CGACTAGTCG)(2) is bound by a short lexitropsin of sequence formyl-PyPy(iPr)Th-Dp (where Py represents N-methyl pyrrole, (iPr)Th represents thiazole with an isopropyl group attached, and Dp represents dimethylaminopropyl). NMR data indicate ligand binding in the minor groove of DNA to the sequence 5'-ACT(5)AG(7)T-3' at a 2:1 ratio of ligand to DNA duplex. Ligand binding, assisted by the enhanced hydrophobicity of the (iPr)Th group, occurs in a head-to-tail fashion, the formyl headgroups being located toward the 5'-ends of the DNA sequence. Sequence reading is augmented through hydrogen bond formation between the exocyclic amine protons of G(7) and the (iPr)Th nitrogen, which lies on the minor groove floor. The B(I)/B(II) DNA backbone equilibrium is altered at the T(5) 3'-phosphate position to accommodate a B(II) configuration. The ligands bind in a staggered mode with respect to one another creating a six base pair DNA reading frame. The introduction of a new DNA sequence-reading element into the recognition jigsaw, combined with an extended reading frame for a small lexitropsin with enhanced hydrophobicity, holds great promise in the development of new, potentially commercially viable drug lead candidates for gene targeting.
About this Structure
1RN9 is a Protein complex structure of sequences from [1]. Full crystallographic information is available from OCA.
Reference
Short lexitropsin that recognizes the DNA minor groove at 5'-ACTAGT-3': understanding the role of isopropyl-thiazole., Anthony NG, Johnston BF, Khalaf AI, MacKay SP, Parkinson JA, Suckling CJ, Waigh RD, J Am Chem Soc. 2004 Sep 15;126(36):11338-49. PMID:15355117
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