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Yorodumi- PDB-1tl3: Crystal structure of hiv-1 reverse transcriptase in complex with ... -
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Entry | Database: PDB / ID: 1tl3 | ||||||
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Title | Crystal structure of hiv-1 reverse transcriptase in complex with gw450557 | ||||||
Components |
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Keywords | TRANSFERASE / HIV-1 REVERSE TRANSCRIPTASE / AIDS / NNRTI / GW450557 / DRUG DESIGN | ||||||
Function / homology | Function and homology information integrase activity / Integration of viral DNA into host genomic DNA / Autointegration results in viral DNA circles / Minus-strand DNA synthesis / Plus-strand DNA synthesis / 2-LTR circle formation / Uncoating of the HIV Virion / Vpr-mediated nuclear import of PICs / Early Phase of HIV Life Cycle / Integration of provirus ...integrase activity / Integration of viral DNA into host genomic DNA / Autointegration results in viral DNA circles / Minus-strand DNA synthesis / Plus-strand DNA synthesis / 2-LTR circle formation / Uncoating of the HIV Virion / Vpr-mediated nuclear import of PICs / Early Phase of HIV Life Cycle / Integration of provirus / APOBEC3G mediated resistance to HIV-1 infection / Binding and entry of HIV virion / viral life cycle / HIV-1 retropepsin / symbiont-mediated activation of host apoptosis / Assembly Of The HIV Virion / retroviral ribonuclease H / exoribonuclease H / Budding and maturation of HIV virion / exoribonuclease H activity / protein processing / host multivesicular body / viral genome integration into host DNA / RNA-directed DNA polymerase / establishment of integrated proviral latency / viral penetration into host nucleus / RNA stem-loop binding / symbiont-mediated suppression of host gene expression / RNA-directed DNA polymerase activity / host cell / RNA-DNA hybrid ribonuclease activity / Transferases; Transferring phosphorus-containing groups; Nucleotidyltransferases / peptidase activity / viral nucleocapsid / aspartic-type endopeptidase activity / DNA recombination / DNA-directed DNA polymerase / Hydrolases; Acting on ester bonds / DNA-directed DNA polymerase activity / symbiont entry into host cell / lipid binding / host cell nucleus / host cell plasma membrane / structural molecule activity / virion membrane / DNA binding / zinc ion binding / identical protein binding / membrane Similarity search - Function | ||||||
Biological species | Human immunodeficiency virus 1 | ||||||
Method | X-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.8 Å | ||||||
Authors | Hopkins, A.L. / Ren, J. / Stuart, D.I. / Stammers, D.K. | ||||||
Citation | Journal: J.Med.Chem. / Year: 2004 Title: Design of non-nucleoside inhibitors of HIV-1 reverse transcriptase with improved drug resistance properties. 1. Authors: Hopkins, A.L. / Ren, J. / Milton, J. / Hazen, R.J. / Chan, J.H. / Stuart, D.I. / Stammers, D.K. #1: Journal: To be Published Title: Design of Non-Nucleoside Inhibitors of HIV-1 Revers Transcriptase with Improved Drug Resistance Propert Part II. Authors: Freeman, G.A. / Andrews III, C.W. / Hopkins, A.L. / Lowell, G.S. / Schaller, L.T. / Cowan, J.L. / Gonzales, S.S. / Koszalka, G.W. / Hazen, R.J. / Boone, L.R. / Ferris, R.G. / Creech, K.L. / ...Authors: Freeman, G.A. / Andrews III, C.W. / Hopkins, A.L. / Lowell, G.S. / Schaller, L.T. / Cowan, J.L. / Gonzales, S.S. / Koszalka, G.W. / Hazen, R.J. / Boone, L.R. / Ferris, R.G. / Creech, K.L. / Short, G.B. / A., Rober S. / Weaver, K. / Reynolds, D.J. / Milton, J. / Ren, J. / Stuart, D.I. / Stammers, D.K. / Chan, J.H. #2: Journal: J.Mol.Biol. / Year: 2004 Title: Crystal Structures of HIV-1 Reverse Transcriptases at Codons 100, 106 and 108 and Mechanisms of Resist Non-Nucleoside Inhibitors Authors: Ren, J. / Nichols, C.E. / Chamberlain, P.P. / Weaver, K.L. / Short, S.A. / Stammers, D.K. #3: Journal: J.Virol. / Year: 2002 Title: Crystal structures of Zidovudine- or Lamivudine-resistant human immunodeficiency virus type 1 reverse transcriptases containing mutations at codons 41, 184, and 215 Authors: Chamberlain, P.P. / Ren, J. / Nichols, C.E. / Douglas, L. / Lennerstrand, J. / Larder, B.A. / Stuart, D.I. / Stammers, D.K. #4: Journal: J.Mol.Biol. / Year: 2001 Title: Structural Mechanisms of Drug Resistance for Mutations at Codons 181 and 188 in HIV-1 Reverse Transcriptase and the Improved Resilience of Second Generation Non-Nucleoside Inhibitors Authors: Ren, J. / Nichols, C. / Bird, L. / Chamberlain, P. / Weaver, K.L. / Short, S.A. / Stuart, D.I. / Stammers, D.K. #5: Journal: J.Med.Chem. / Year: 2001 Title: 2-Amino-6-Arylsulfonylbenzonitriles as Non-Nucleosi Transcriptase Inhibitors of HIV-1 Authors: Chan, J.H. / Hong, J.S. / Hunter III, R.N. / Orr, G.F. / Cowan, J.R. / Sherman, D.B. / Sparks, S.M. / Reitter, B.E. / Hazen, C.W. / Andrews III, R.J. / St Clair, M. / Boone, L.R. / Ferris, R. ...Authors: Chan, J.H. / Hong, J.S. / Hunter III, R.N. / Orr, G.F. / Cowan, J.R. / Sherman, D.B. / Sparks, S.M. / Reitter, B.E. / Hazen, C.W. / Andrews III, R.J. / St Clair, M. / Boone, L.R. / Ferris, R.G. / Roberts, K.L. / Cree, G.B. / Short, S.A. / Weaver, K. / Ott, R.J. / Ren, J. / Hopkins, A. / Stuart, D.I. / Stammers, D.K. #6: Journal: Structure / Year: 2000 Title: Structural Basis for the Resilience of Efavirenz (Dmp-266) to Drug Resistant Mutations in HIV-1 Reverse Transcriptase Authors: Ren, J. / Milton, J. / Weaver, K.L. / Short, S.A. / Stuart, D.I. / Stammers, D.K. #7: Journal: J.Biol.Chem. / Year: 2000 Title: Binding of the Second Generattion Non-Nucleoside Inhibitor S-1153 to HIV-1 Reverse Transcriptase Involves Extensive Main Chain Hydrogen Bonding Authors: Ren, J. / Nichols, C. / Bird, L.E. / Fujiwara, T. / Suginoto, H. / Stuart, D.I. / Stammers, D.K. #8: Journal: J.Biol.Chem. / Year: 2000 Title: Phenethylthiazolylthiourea (Pett) Non-Nucleoside Inhibitors of HIV-1 and HIV-2 Reverse Transcriptases: Structural and Biochemical Analyses Authors: Ren, J. / Diprose, J. / Warren, J. / Esnouf, R.M. / Bird, L.E. / Ikemizu, S. / Slater, M. / Milton, J. / Balzarini, J. / Stuart, D.I. / Stammers, D.K. #9: Journal: J.Med.Chem. / Year: 1999 Title: Crystallographic Analysis of the Binding Modes of Non-Nucleoside Thiazoloisoindolinone Inhibitors to HIV-1 Reverse Transcriptase and Comparison with Modeling Studies Authors: Ren, J. / Esnouf, R.M. / Hopkins, A.L. / Stuart, D.I. / Stammers, D.K. #10: Journal: J.Med.Chem. / Year: 1999 Title: Design of Mkc-442 (Emivirine) Analogues with Improved Activity Against Drug-Resistant HIV Mutants Authors: Hopkins, A.L. / Ren, J. / Tanaka, H. / Baba, M. / Okamato, M. / Stuart, D.I. / Stammers, D.K. #11: Journal: Biochemistry / Year: 1998 Title: Crystal Structures of Reverse Transcriptase in Complex with Carboxanilide Derivatives Authors: Ren, J. / Esnouf, R.M. / Hopkins, A.L. / Warren, J. / Balzarini, J. / Stuart, D.I. / Stammers, D.K. #12: Journal: Proc.Natl.Acad.Sci.USA / Year: 1998 Title: 3'-Azido-3'-Deoxythymidine Drug Resistance Mutations in HIV-1 Reverse Transcriptase Can Induce Long Range Conformational Changes Authors: Ren, J. / Esnouf, R.M. / Hopkins, A.L. / Jones, E.Y. / Kirby, I. / Keeling, J. / Ross, C.K. / Larder, B.A. / Stuart, D.I. / Stammers, D.K. #13: Journal: Acta Crystallogr.,Sect.D / Year: 1998 Title: Continuous and Discontinuous Changes in the Unit Cell of HIV-1 Reverse Transcriptase Crystals on Dehydration Authors: Esnouf, R.M. / Ren, J. / Garman, E. / Somers, D.O. / Ross, C.K. / Jones, E.Y. / Stammers, D.K. / Stuart, D.I. #14: Journal: Proc.Natl.Acad.Sci.USA / Year: 1997 Title: Unique Features in the Structure of the Complex between HIV-1 Reverse Transcriptase and the Bis(Heteroaryl)Piperazine (Bhap) U-90152 Explain Resistance Mutations for This Non-Nucleoside Inhibitor Authors: Esnouf, R.M. / Ren, J. / Hopkins, A.L. / Ross, C.K. / Jones, E.Y. / Stammers, D.K. / Stuart, D.I. #15: Journal: J.Med.Chem. / Year: 1996 Title: Complexes of HIV-1 Reverse Transcriptase with Inhibitors of the HEPT Series Reveal Conformational Changes Relevant to the Design of Potent Non-Nucleoside Inhibitors Authors: L Hopkins, A. / Ren, J. / Esnouf, R.M. / Willcox, B.E. / Jones, E.Y. / Ross, C.K. / Miyasaka, T. / Walker, R.T. / Tanaka, H. / Stammers, D.K. / Stuart, D.I. #16: Journal: Structure / Year: 1995 Title: The Structure of HIV-1 Reverse Transcriptase Complexed with 9-Chloro-TIBO: Lessons for Inhibitor Design Authors: Ren, J. / Esnouf, R.M. / Hopkins, A.L. / Ross, C.K. / Jones, E.Y. / Stammers, D.K. / Stuart, D.I. #17: Journal: Nat.Struct.Biol. / Year: 1995 Title: High Resolution Structures of HIV-1 RT from Four RT-Inhibitor Complexes Authors: Ren, J. / Esnouf, R.M. / Garman, E. / Somers, D.O. / Ross, C.K. / Kirby, I. / Keeling, J. / Darby, G. / Jones, E.Y. / Stuart, D.I. / Stammers, D.K. #18: Journal: Nat.Struct.Biol. / Year: 1995 Title: Mechanism of Inhibition of HIV-1 Reverse Transcriptase by Non-Nucleoside Inhibitors Authors: Esnouf, R.M. / Ren, J. / Ross, C.K. / Jones, E.Y. / Stammers, D.K. / Stuart, D.I. #19: Journal: J.Mol.Biol. / Year: 1994 Title: Crystals of HIV-1 Reverse Transcriptase Diffracting to 2.2 Angstrom Resolution Authors: Stammers, D.K. / Somers, D.O. / Ross, C.K. / Kirby, I. / Ray, P.H. / Wilson, J.E. / Norman, M. / Ren, J. / Esnouf, R.M. / Garman, E. / Jones, E.Y. / Stuart, D.I. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 1tl3.cif.gz | 198.1 KB | Display | PDBx/mmCIF format |
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PDB format | pdb1tl3.ent.gz | 160.9 KB | Display | PDB format |
PDBx/mmJSON format | 1tl3.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 1tl3_validation.pdf.gz | 762.8 KB | Display | wwPDB validaton report |
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Full document | 1tl3_full_validation.pdf.gz | 805 KB | Display | |
Data in XML | 1tl3_validation.xml.gz | 38.1 KB | Display | |
Data in CIF | 1tl3_validation.cif.gz | 51 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/tl/1tl3 ftp://data.pdbj.org/pub/pdb/validation_reports/tl/1tl3 | HTTPS FTP |
-Related structure data
-Links
-Assembly
Deposited unit |
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1 |
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Unit cell |
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-Components
#1: Protein | Mass: 64594.949 Da / Num. of mol.: 1 / Fragment: P66 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Human immunodeficiency virus 1 / Genus: Lentivirus / Strain: HXB2 ISOLATE / Gene: Name=POL; / Production host: Escherichia coli (E. coli) / References: UniProt: P04585, RNA-directed DNA polymerase | ||
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#2: Protein | Mass: 51399.047 Da / Num. of mol.: 1 / Fragment: P51 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Human immunodeficiency virus 1 / Genus: Lentivirus / Strain: HXB2 ISOLATE / Gene: Name=POL; / Production host: Escherichia coli (E. coli) / References: UniProt: P04585, RNA-directed DNA polymerase | ||
#3: Chemical | #4: Chemical | ChemComp-H20 / | |
-Experimental details
-Experiment
Experiment | Method: X-RAY DIFFRACTION / Number of used crystals: 1 |
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-Sample preparation
Crystal | Density Matthews: 2.24 Å3/Da / Density % sol: 45.03 % |
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-Data collection
Diffraction | Mean temperature: 100 K |
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Diffraction source | Source: SYNCHROTRON / Site: SRS / Beamline: PX7.2 / Wavelength: 1.488 Å |
Detector | Type: MARRESEARCH / Detector: IMAGE PLATE / Date: Aug 10, 1997 |
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 1.488 Å / Relative weight: 1 |
Reflection | Resolution: 2.8→30 Å / Num. obs: 24466 / % possible obs: 92.1 % / Observed criterion σ(I): -1.5 / Redundancy: 2.88 % / Biso Wilson estimate: 66.4 Å2 / Rmerge(I) obs: 0.103 / Net I/σ(I): 9.74 |
Reflection shell | Resolution: 2.8→2.9 Å / Redundancy: 2.18 % / Rmerge(I) obs: 0.408 / Mean I/σ(I) obs: 1.6 / Num. unique all: 2186 / % possible all: 83.3 |
-Processing
Software |
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Refinement | Method to determine structure: MOLECULAR REPLACEMENT / Resolution: 2.8→29.85 Å / Rfactor Rfree error: 0.008 / Data cutoff high absF: 2170610.69 / Data cutoff low absF: 0 / Isotropic thermal model: RESTRAINED / Cross valid method: THROUGHOUT / σ(F): 0 Details: DUE TO THE LOW RATIO BETWEEN THE NUMBER OF REFLECTIONS AND THE R APPLIED TO ALL ATOMS DISTANT FROM THE NNRTI-BINDING SITE(DEFINED AS ATOMS MORE THAN 20 ANGSTROM FROM THE CA ATOM OF TYR188) ...Details: DUE TO THE LOW RATIO BETWEEN THE NUMBER OF REFLECTIONS AND THE R APPLIED TO ALL ATOMS DISTANT FROM THE NNRTI-BINDING SITE(DEFINED AS ATOMS MORE THAN 20 ANGSTROM FROM THE CA ATOM OF TYR188) THROUGHOUT THE REFINEMENT.
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Solvent computation | Solvent model: FLAT MODEL / Bsol: 28.0578 Å2 / ksol: 0.308248 e/Å3 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Displacement parameters | Biso mean: 61.7 Å2
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Refine analyze |
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Refinement step | Cycle: LAST / Resolution: 2.8→29.85 Å
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Refine LS restraints |
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LS refinement shell | Resolution: 2.8→2.9 Å / Rfactor Rfree error: 0.037 / Total num. of bins used: 10
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Xplor file |
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