Crystals of the large ribosomal subunit

Details Crystals of the large ribosomal subunit Crystals of the large ribosomal subunit

2005-09-06

2005-09-06

Allen, Marianne P. (Department: 1631)

Drug, bio-affecting and body treating compositions

Designated organic active ingredient containing

Peptide containing doai

C702S027000, C702S019000, C530S350000

Reexamination Certificate

active

06939848

ABSTRACT:
The present invention provides methods for producing high resolution crystals of ribosomes and ribosomal subunits as well as the crystals produced by such methods. The x-ray diffraction patterns of the crystals provided by the present invention are of sufficiently high resolution for determining the three-dimensional structure of ribosomes and ribosomal subunits, for identifying ligand binding sites on ribosomes and ribosomal subunits, and for molecular modeling of ligands which interact with ribosomes and ribosomal subunits. The present invention provides methods for identifying ribosome-related ligands and methods for designing ligands with specific ribosome-binding properties. Thus, the methods of the present invention may be used to produce ligands which are designed to kill or inhibit any specific target organism(s).

REFERENCES:
patent: 5180719 (1993-01-01), White et al.
patent: 5281703 (1994-01-01), White et al.
patent: 5336768 (1994-08-01), Albrecht et al.
patent: 5466681 (1995-11-01), Krivan et al.
patent: 5693791 (1997-12-01), Truett
patent: 5866549 (1999-02-01), Or et al.
patent: 5905144 (1999-05-01), Truett
patent: 6380356 (2002-04-01), Griffin et al.
patent: 6437119 (2002-08-01), Truett
patent: 6446032 (2002-09-01), Schimmel
patent: 6468979 (2002-10-01), Pellacini et al.
patent: 6638908 (2003-10-01), Steitz et al.
patent: 2002/0022257 (2002-02-01), Suh et al.
patent: 2002/0086308 (2002-07-01), Steitz et al.
patent: 2002/0188108 (2002-12-01), Noller et al.
patent: 2003/0027315 (2003-02-01), Yonath et al.
patent: 1 172 374 (2002-01-01), None
patent: 1 186 614 (2002-03-01), None
patent: 1 188 769 (2002-03-01), None
patent: WO 95/07271 (1995-03-01), None
patent: WO 96/18633 (1996-06-01), None
patent: WO 97/35195 (1997-09-01), None
patent: WO 99/63937 (1999-12-01), None
patent: WO 00/32619 (2000-06-01), None
patent: WO 01/80863 (2001-11-01), None
Hansen et al. (2003) “Structures of Five Antibiotics Bound at the Peptidyl Transferase Center of the Large Ribosomal Subunit,”Journal of Molecular Biology, vol. 330, pp. 1061-1075.
Agalarov, S,. et al., (2000) “Structure of the S15, S6, S18-rRNA Complex: Assembly of the 30S Ribosome Central Domain,”Sciencevol. 288, pp. 107-112.
Agrawal, R., et al., (1998) “Visualization of Elongation Factor G on theEscherichia coli70S Ribosome: The Mechanism of Translocation,”Proc. Natl. Acad. Sci. USAvol. 95, pp. 6134-6138.
Ban, N., et al., (2000) “The Complete Atomic Structure of the Large Ribosomal Subunit at 2.4 Å Resolution,”Sciencevol. 289, No. 5481, pp. 821-1096.
Ban, N., et al., (1999) “Placement of Protein and RNA Structures into a 5 Å-Resolution Map of the 50S Ribosomal Subunit,”Naturevol. 400, pp. 841-847.
Ban, N., et al., (1998) “A 9 Å Resolution X-Ray Crystallographic Map of the Large Ribosomal Subunit,”Cellvol. 93, pp. 1105-1115.
Baranov, P., et al., (1998) “The Database of Ribosomal Cross Links (DRC),”Nucleic Acids Researchvol. 26, No. 1, pp. 187-189.
Brodersen, D., et al., (2000) “The Structural Basis for the Action of the Antibiotics Tetracycline, Pactamycin, and Hygromycin B on the 30S Ribosomal Subunit,”Cellvol. 103, pp. 1143-1154.
Brünger, A., et al., (1998) “Crystallography&NMR System: A New Software Suite for Macromolecular Structure Determination,”Acta Cryst. vol. D54, pp. 905-921.
Brünger, A., (1997) “Patterson Correlation Searches and Refinement,”Methods in Enzymology, vol. 276, pp. 558-580.
Carter, A., et al., (2001) “Crystal Structure of an Initiation Factor Bound to the 30S Ribosomal Subunit,”Sciencevol. 291, pp. 498-501.
Carter, A., et al., (2000) “Functional Insights from the Structure of the 30S Ribosomal Subunit and It's Interactions with Antibiotics,”Naturevol. 407, pp. 340-348.
Cate, J., et al., (1999) “X-Ray Crystal Structures of 70S Ribosome Functional Complexes,”Sciencevol. 285, No. 5, pp. 2095-2104.
Clemons, W. Jr., et al., (1999) “Structure of a Bacterial 30S Ribosomal Subunit at 5.5 Å Resolution,”Naturevol. 400, pp. 833-840.
Culver, G., et al., (1999) “Identification of an RNA-Protein Bridge Spanning the Ribosomal Subunit Interface,”Sciencevol. 285, pp. 2133-2135.
Dahlberg, A., et al., (2001) “The Ribosome in Action,”Sciencevol. 292, pp. 868-869.
Davies, C. et al., (1998) “Ribosomal Proteins S5 and L6: High-Resolution Crystal Structures and Roles in Protein Synthesis and Antibiotic Resistance,”Journal of Molecular Biology, vol. 279, pp. 873-888.
Di Giambattista, M., et al., (1990) “Affinity Labeling of the Virginiamycin S. Binding Site on Bacterial Ribosome,”Biochemistryvol. 29, pp. 9203-9211.
Douthwaite, S., et al., (1995) “Recognition Determinants for Proteins and Antibiotics within 23S rRNA,”Biochem. Cell Biol. vol. 73, pp. 1179-1185.
Douthwaite, S., et al., (1993) “Erythromycin Binding is Reduced in Ribosomes with Conformational Alterations in the 23 S rRNA Peptidyl Transferase Loop,”Journal Mol. Biol. vol. 232, pp. 725-731.
Douthwaite, (1992) “Functional Interactions within 23S rRNA Involving the Peptidyltransferase Center,”Journal of Bacteriologyvol. 174, No. 4, pp. 1333-1338.
Fitzhugh, A., et al., (1998) “Antibiotic Inhibitors of the Peptidyl Transferase Center. 1. Clindamycin as a Composite Analogue of the Transfer RNA Fragments L-Pro-Met and the D-Ribosyl Ring of Adenosine,”Bioorganic and Medicinal Chemistry Letters, vol. 8, pp. 87-92.
Gabashvili, I., et al., (2000) “Solution Structure of theE coli70S Ribosome at 11.5 Å Resolution,”Cell, vol. 100, pp. 537-549.
Garrett, R., et al., (1996) “The Peptidyl Transferase Center,”Ribosomal RNApp. 327-355.
Garza-Ramos, G. et al., (2001) “Binding Site of Macrolide Antibiotics on the Ribosome: New Resistance Mutation Identifies a Specific Interaction of Ketolides with rRNA,”Journal of Bacteriology, vol. 183, No. 23, pp. 6898-6907.
Gonzales, R., et al., (2001) “Infections Due to Vancomycin-ResistantEnterococcus faeciumResistant to Iinezolid,”The Lancetvol. 357, p. 1179.
Green, R., et al., (1997) “Ribosomes and Translation,”Annu. Rev. Biochemistryvol. 66, pp. 679-716.
Gregory, S., et al., (1999) “Erythromycin Resistance Mutations in Ribosomal Proteins L22 and L4 Perturb the Higher Order Structure of 23 S Ribosomal RNA,”J. Mol. Biol. vol. 289, pp. 827-834.
Gschwend, D. et al., (1996) “Molecular Docking Towards Drug Discovery,”Journal of Molecular Recognition, vol. 9, pp. 175-186.
Guetell, R. (1996) “Comparative Sequence Analysis and the Structure of 16S and 23S rRNA,”Ribosomal RNApp. 111-128.
Hansen, H.A.S., et al., (1990) “Crystals of Complexes Mimicking Protein Biosynthesis are Suitable for Crystallographic Studies,”Bioclumica et Biophysica Acta. vol. 1050, pp. 1-7.
Harms, J., et al., (2001) “High Resolution Structure of the Large Ribosomal Subunit from a Mesophilic Eubacterium,”Cell, vol. 107, pp. 679-688.
Harms, J., et al., (1999) “Elucidating the Medium-Resolution Structure of Ribosomal Particles: an Interplay between Electron Cryo-Microscopy and X-ray Crystallography,”Structurevol. 7, No. 8, pp. 931-941.
Hansen, L., et al., (1999) “The Macrolide-Ketolide Antibiotic Binding Site is Formed by Structures in Domains II and V of 23S Ribosomal RNA,”Molecular Microbiology, vol. 31, No. 2, pp. 623-631.
Kloss, P., et al., (1999) “ Resistance Mutations in 23 S rRNA Identify the Site of Action of the Protein Synthesis Inhibitor Linezolid in the Ribosomal Peptidyl Transferase Center,”J. Mol. Biol. vol. 294, No. 1, pp. 93-101.
Lázaro, E., et al., (1996) “A Sparsomycin-Resistant Mutant ofHalobacterium salinariumLacks a Modification at Nucleotide U2603 in the Peptidyl Transferase Centre of 23 S rRNA,”J. Mol. Biol. vol. 2

Affiliated with

Also associated with

Rating

Crystals of the large ribosomal subunit does not yet have a rating. At this time, there are no reviews or comments for this patent.

If you have personal experience with Crystals of the large ribosomal subunit, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Crystals of the large ribosomal subunit will most certainly appreciate the feedback.

Rate now

Comments { 0 }

Profile ID: LFUS-PAI-O-3370381