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Yorodumi- PDB-2iaj: Crystal Structure of K103N/Y181C Mutant HIV-1 Reverse Transcripta... -
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-Basic information
Entry | Database: PDB / ID: 2iaj | ||||||
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Title | Crystal Structure of K103N/Y181C Mutant HIV-1 Reverse Transcriptase (RT) in Complex with ATP | ||||||
Components | (Reverse transcriptase/ribonuclease ...) x 2 | ||||||
Keywords | TRANSFERASE / RT / NNRTI / NONNUCLEOSIDE INHIBITOR / DRUG RESISTANCE / DNA POLYMERIZATION / HIV / AIDS / DRUG DESIGN | ||||||
Function / homology | Function and homology information HIV-1 retropepsin / : / retroviral ribonuclease H / exoribonuclease H / : / exoribonuclease H activity / host multivesicular body / DNA integration / viral genome integration into host DNA / RNA-directed DNA polymerase ...HIV-1 retropepsin / : / retroviral ribonuclease H / exoribonuclease H / : / exoribonuclease H activity / host multivesicular body / DNA integration / viral genome integration into host DNA / RNA-directed DNA polymerase / establishment of integrated proviral latency / viral penetration into host nucleus / RNA-directed DNA polymerase activity / Transferases; Transferring phosphorus-containing groups; Nucleotidyltransferases / RNA-DNA hybrid ribonuclease activity / viral nucleocapsid / DNA recombination / Hydrolases; Acting on ester bonds / DNA-directed DNA polymerase / aspartic-type endopeptidase activity / DNA-directed DNA polymerase activity / symbiont entry into host cell / symbiont-mediated suppression of host gene expression / lipid binding / host cell nucleus / structural molecule activity / host cell plasma membrane / virion membrane / proteolysis / DNA binding / RNA binding / zinc ion binding / membrane Similarity search - Function | ||||||
Biological species | Human immunodeficiency virus type 1 BH10 | ||||||
Method | X-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.5 Å | ||||||
Authors | Das, K. / Arnold, E. | ||||||
Citation | Journal: J.Mol.Biol. / Year: 2007 Title: Crystal Structures of Clinically Relevant Lys103Asn/Tyr181Cys Double Mutant HIV-1 Reverse Transcriptase in Complexes with ATP and Non-nucleoside Inhibitor HBY 097. Authors: Das, K. / Sarafianos, S.G. / Clark, A.D. / Boyer, P.L. / Hughes, S.H. / Arnold, E. #1: Journal: Structure / Year: 1996 Title: Structure of Unliganded HIV-1 Reverse Transcriptase at 2.7 A Resolution: Implications of Conformational Changes for Polymerization and Inhibition Mechanisms Authors: Hsiou, Y. / Ding, J. / Das, K. / D Clark, A. / Hughes, S.H. / Arnold, E. #2: Journal: J.Mol.Biol. / Year: 1996 Title: Crystal structures of 8-Cl and 9-Cl TIBO complexed with wild-type HIV-1 RT and 8-Cl TIBO complexed with the Tyr181Cys HIV-1 RT drug-resistant mutant. Authors: Das, K. / Ding, J. / Hsiou, Y. / Clark, A.D. / Moereels, H. / Koymans, L. / Andries, K. / Pauwels, R. / Janssen, P.A. / Boyer, P.L. / Clark, P. / Smith, R.H. / Kroeger Smith, M.B. / ...Authors: Das, K. / Ding, J. / Hsiou, Y. / Clark, A.D. / Moereels, H. / Koymans, L. / Andries, K. / Pauwels, R. / Janssen, P.A. / Boyer, P.L. / Clark, P. / Smith, R.H. / Kroeger Smith, M.B. / Michejda, C.J. / Hughes, S.H. / Arnold, E. #3: Journal: J.Mol.Biol. / Year: 1998 Title: Structures of Tyr188Leu mutant and wild-type HIV-1 reverse transcriptase complexed with the non-nucleoside inhibitor HBY 097: inhibitor flexibility is a useful design feature for reducing drug resistance. Authors: Hsiou, Y. / Das, K. / Ding, J. / Clark, A.D. / Kleim, J.P. / Winkler, I. / Riess, G. / Hughes, S.H. / Arnold, E. #4: Journal: J.Mol.Biol. / Year: 2001 Title: The Lys103Asn mutation of HIV-1 RT: a novel mechanism of drug resistance. Authors: Hsiou, Y. / Ding, J. / Das, K. / Clark, A.D. / Boyer, P.L. / Lewi, P. / Janssen, P.A. / Kleim, J.P. / Hughes, S.H. / Arnold, E. #5: Journal: J.Med.Chem. / Year: 2004 Title: Roles of conformational and positional adaptability in structure-based design of TMC125-R165335 (etravirine) and related non-nucleoside reverse transcriptase inhibitors that are highly potent ...Title: Roles of conformational and positional adaptability in structure-based design of TMC125-R165335 (etravirine) and related non-nucleoside reverse transcriptase inhibitors that are highly potent and effective against wild-type and drug-resistant HIV-1 variants. Authors: Das, K. / Clark, A.D. / Lewi, P.J. / Heeres, J. / De Jonge, M.R. / Koymans, L.M. / Vinkers, H.M. / Daeyaert, F. / Ludovici, D.W. / Kukla, M.J. / De Corte, B. / Kavash, R.W. / Ho, C.Y. / Ye, ...Authors: Das, K. / Clark, A.D. / Lewi, P.J. / Heeres, J. / De Jonge, M.R. / Koymans, L.M. / Vinkers, H.M. / Daeyaert, F. / Ludovici, D.W. / Kukla, M.J. / De Corte, B. / Kavash, R.W. / Ho, C.Y. / Ye, H. / Lichtenstein, M.A. / Andries, K. / Pauwels, R. / Boyer, P.L. / Clark, P. / Hughes, S.H. / Janssen, P.A. / Arnold, E. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 2iaj.cif.gz | 219.7 KB | Display | PDBx/mmCIF format |
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PDB format | pdb2iaj.ent.gz | 172.4 KB | Display | PDB format |
PDBx/mmJSON format | 2iaj.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/ia/2iaj ftp://data.pdbj.org/pub/pdb/validation_reports/ia/2iaj | HTTPS FTP |
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-Related structure data
Related structure data | 2ic3C 1dloS S: Starting model for refinement C: citing same article (ref.) |
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Similar structure data |
-Links
-Assembly
Deposited unit |
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1 |
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Unit cell |
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Details | p66/p51 hetero dimer |
-Components
-Reverse transcriptase/ribonuclease ... , 2 types, 2 molecules AB
#1: Protein | Mass: 64425.855 Da / Num. of mol.: 1 / Fragment: p66 / Mutation: K103N, Y181C, C280S Source method: isolated from a genetically manipulated source Source: (gene. exp.) Human immunodeficiency virus type 1 BH10 Genus: Lentivirus / Species: Human immunodeficiency virus 1Subtypes of HIV / Strain: BH10 ISOLATE / Gene: pol / Production host: Escherichia coli (E. coli) / References: UniProt: P03366, RNA-directed DNA polymerase |
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#2: Protein | Mass: 51970.562 Da / Num. of mol.: 1 / Fragment: p51 / Mutation: K103N, Y181C, C280S Source method: isolated from a genetically manipulated source Source: (gene. exp.) Human immunodeficiency virus type 1 BH10 Genus: Lentivirus / Species: Human immunodeficiency virus 1Subtypes of HIV / Strain: BH10 ISOLATE / Gene: pol / Production host: Escherichia coli (E. coli) / References: UniProt: P03366, RNA-directed DNA polymerase |
-Non-polymers , 5 types, 315 molecules
#3: Chemical | #4: Chemical | ChemComp-NA / | #5: Chemical | ChemComp-ATP / | #6: Chemical | #7: Water | ChemComp-HOH / | |
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-Experimental details
-Experiment
Experiment | Method: X-RAY DIFFRACTION / Number of used crystals: 1 |
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-Sample preparation
Crystal | Density Matthews: 3.35 Å3/Da / Density % sol: 63.24 % |
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Crystal grow | Temperature: 277 K / Method: vapor diffusion, hanging drop / pH: 6.8 Details: PEG 8000, Bis_Tris propane, ammonium sulfate, glycerol, MnCL2, ATP, VAPOR DIFFUSION, HANGING DROP, temperature 277K, pH 6.8 |
-Data collection
Diffraction | Mean temperature: 100 K |
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Diffraction source | Source: SYNCHROTRON / Site: APS / Beamline: 14-BM-C / Wavelength: 1 Å |
Detector | Type: ADSC QUANTUM 4 / Detector: CCD / Date: Oct 12, 2000 |
Radiation | Monochromator: GRAPHITE / Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 1 Å / Relative weight: 1 |
Reflection | Resolution: 2.5→40 Å / Num. obs: 48538 / % possible obs: 92.2 % / Observed criterion σ(I): -1 / Rmerge(I) obs: 0.057 / Χ2: 0.92 / Net I/σ(I): 15.2 |
Reflection shell | Resolution: 2.5→2.54 Å / Rmerge(I) obs: 0.367 / Num. unique all: 1809 / Χ2: 1.219 / % possible all: 68.5 |
-Processing
Software |
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Refinement | Method to determine structure: MOLECULAR REPLACEMENT Starting model: 1DLO Resolution: 2.5→19.96 Å / Rfactor Rfree error: 0.007 / Data cutoff high absF: 789848.625 / Data cutoff low absF: 0 / Isotropic thermal model: RESTRAINED / Cross valid method: THROUGHOUT / σ(F): 1 / Stereochemistry target values: Engh & Huber
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Solvent computation | Solvent model: FLAT MODEL / Bsol: 40.368 Å2 / ksol: 0.283 e/Å3 | ||||||||||||||||||||||||||||||||||||
Displacement parameters | Biso mean: 72.6 Å2
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Refine analyze |
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Refinement step | Cycle: LAST / Resolution: 2.5→19.96 Å
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Refine LS restraints |
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LS refinement shell | Resolution: 2.5→2.66 Å / Rfactor Rfree error: 0.035 / Total num. of bins used: 6
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Xplor file |
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