[English] 日本語
Yorodumi
- PDB-4k4p: TL-3 inhibited Trp6Ala HIV Protease -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 4k4p
TitleTL-3 inhibited Trp6Ala HIV Protease
ComponentsHIV-1 protease
KeywordsHYDROLASE/HYDROLASE INHIBITOR / fragment binding / exosite / protease / HYDROLASE-HYDROLASE INHIBITOR complex
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 / establishment of integrated proviral latency / viral penetration into host nucleus ...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 stem-loop binding / RNA-directed DNA polymerase activity / host cell / RNA-DNA hybrid ribonuclease activity / Transferases; Transferring phosphorus-containing groups; Nucleotidyltransferases / symbiont-mediated suppression of host gene expression / viral nucleocapsid / DNA recombination / DNA-directed DNA polymerase / Hydrolases; Acting on ester bonds / aspartic-type endopeptidase activity / DNA-directed DNA polymerase activity / symbiont entry into host cell / lipid binding / host cell nucleus / host cell plasma membrane / structural molecule activity / virion membrane / proteolysis / DNA binding / zinc ion binding / membrane
Similarity search - Function
Reverse transcriptase connection / Reverse transcriptase connection domain / Reverse transcriptase thumb / Reverse transcriptase thumb domain / Integrase Zinc binding domain / Zinc finger integrase-type profile. / Integrase-like, N-terminal / Integrase DNA binding domain / Integrase, C-terminal domain superfamily, retroviral / Integrase, N-terminal zinc-binding domain ...Reverse transcriptase connection / Reverse transcriptase connection domain / Reverse transcriptase thumb / Reverse transcriptase thumb domain / Integrase Zinc binding domain / Zinc finger integrase-type profile. / Integrase-like, N-terminal / Integrase DNA binding domain / Integrase, C-terminal domain superfamily, retroviral / Integrase, N-terminal zinc-binding domain / Integrase, C-terminal, retroviral / Integrase DNA binding domain profile. / Immunodeficiency lentiviral matrix, N-terminal / gag gene protein p17 (matrix protein) / RNase H / Integrase core domain / Integrase, catalytic core / Integrase catalytic domain profile. / Retroviral nucleocapsid Gag protein p24, C-terminal domain / Gag protein p24 C-terminal domain / Retropepsin-like catalytic domain / Matrix protein, lentiviral and alpha-retroviral, N-terminal / Ribonuclease H domain / RNase H type-1 domain profile. / Reverse transcriptase (RNA-dependent DNA polymerase) / Reverse transcriptase domain / Reverse transcriptase (RT) catalytic domain profile. / Retropepsins / Retroviral aspartyl protease / Aspartyl protease, retroviral-type family profile. / Peptidase A2A, retrovirus, catalytic / Retrovirus capsid, C-terminal / Retroviral matrix protein / Retrovirus capsid, N-terminal / zinc finger / Zinc knuckle / Cathepsin D, subunit A; domain 1 / Acid Proteases / Zinc finger, CCHC-type superfamily / Zinc finger, CCHC-type / Zinc finger CCHC-type profile. / Aspartic peptidase, active site / Eukaryotic and viral aspartyl proteases active site. / Ribonuclease H superfamily / Aspartic peptidase domain superfamily / Ribonuclease H-like superfamily / Reverse transcriptase/Diguanylate cyclase domain / DNA/RNA polymerase superfamily / Beta Barrel / Mainly Beta
Similarity search - Domain/homology
N-[(benzyloxy)carbonyl]-L-alanyl-N-[(1R)-1-benzyl-2-oxoethyl]-L-valinamide / Chem-3TL / NITRATE ION / Gag-Pol polyprotein
Similarity search - Component
Biological speciesHuman immunodeficiency virus type 1
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / molecular replacement / Resolution: 2.31 Å
AuthorsTiefenbrunn, T. / Stout, C.D.
CitationJournal: Chem.Biol.Drug Des. / Year: 2014
Title: Crystallographic Fragment-Based Drug Discovery: Use of a Brominated Fragment Library Targeting HIV Protease.
Authors: Tiefenbrunn, T. / Forli, S. / Happer, M. / Gonzalez, A. / Tsai, Y. / Soltis, M. / Elder, J.H. / Olson, A.J. / Stout, C.D.
History
DepositionApr 12, 2013Deposition site: RCSB / Processing site: RCSB
Revision 1.0Sep 18, 2013Provider: repository / Type: Initial release
Revision 1.1Oct 16, 2013Group: Non-polymer description
Revision 1.2Feb 12, 2014Group: Database references
Revision 1.3Feb 28, 2024Group: Data collection / Database references / Derived calculations
Category: chem_comp_atom / chem_comp_bond ...chem_comp_atom / chem_comp_bond / database_2 / struct_ref_seq_dif / struct_site
Item: _database_2.pdbx_DOI / _database_2.pdbx_database_accession ..._database_2.pdbx_DOI / _database_2.pdbx_database_accession / _struct_ref_seq_dif.details / _struct_site.pdbx_auth_asym_id / _struct_site.pdbx_auth_comp_id / _struct_site.pdbx_auth_seq_id

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: HIV-1 protease
B: HIV-1 protease
hetero molecules


Theoretical massNumber of molelcules
Total (without water)22,4044
Polymers21,4332
Non-polymers9712
Water36020
1


  • Idetical with deposited unit
  • defined by author&software
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area5360 Å2
ΔGint-28 kcal/mol
Surface area9380 Å2
MethodPISA
Unit cell
Length a, b, c (Å)98.505, 98.505, 96.409
Angle α, β, γ (deg.)90.00, 90.00, 90.00
Int Tables number98
Space group name H-MI4122
Components on special symmetry positions
IDModelComponents
11B-202-

HOH

21B-205-

HOH

31B-206-

HOH

-
Components

#1: Protein HIV-1 protease


Mass: 10716.701 Da / Num. of mol.: 2 / Mutation: W6A
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Human immunodeficiency virus type 1 / Gene: gag-pol / Plasmid: pET-21a(+) / Production host: Escherichia coli (E. coli) / Strain (production host): Rosetta2(DE3) pLysS / References: UniProt: P12499, HIV-1 retropepsin
#2: Chemical ChemComp-NO3 / NITRATE ION


Mass: 62.005 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: NO3
#3: Chemical ChemComp-3TL / benzyl [(1S,4S,7S,8R,9R,10S,13S,16S)-7,10-dibenzyl-8,9-dihydroxy-1,16-dimethyl-4,13-bis(1-methylethyl)-2,5,12,15,18-pentaoxo-20-phenyl-19-oxa-3,6,11,14,17-pentaazaicos-1-yl]carbamate / TL-3, C2 symmetric inhibitor


Type: peptide-like, Peptide-like / Class: Inhibitor / Mass: 909.077 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C50H64N6O10
References: N-[(benzyloxy)carbonyl]-L-alanyl-N-[(1R)-1-benzyl-2-oxoethyl]-L-valinamide
#4: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 20 / Source method: isolated from a natural source / Formula: H2O
Sequence detailsTHESE SEQUENCE CONFLICTS REPRESENT CLONAL VARIABILITY WITHIN HIV-1

-
Experimental details

-
Experiment

ExperimentMethod: X-RAY DIFFRACTION / Number of used crystals: 1

-
Sample preparation

CrystalDensity Matthews: 2.73 Å3/Da / Density % sol: 54.91 %
Crystal growTemperature: 298 K / Method: vapor diffusion / pH: 5
Details: 0.1M NaOAc pH 5.0, 2.5M NaNO3, vapor diffusion, temperature 298K

-
Data collection

DiffractionMean temperature: 100 K
Diffraction sourceSource: SYNCHROTRON / Site: SSRL / Beamline: BL11-1 / Wavelength: 0.918 Å
DetectorType: PSI PILATUS 6M / Detector: PIXEL / Date: Mar 23, 2012 / Details: Rh Coated flat mirror
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.918 Å / Relative weight: 1
ReflectionResolution: 2.309→34.85 Å / Num. all: 10686 / Num. obs: 10686 / % possible obs: 99.5 % / Redundancy: 6.4 % / Rsym value: 0.029 / Net I/σ(I): 29.8
Reflection shell
Resolution (Å)Redundancy (%)Rmerge(I) obsMean I/σ(I) obsRsym valueDiffraction-ID% possible all
2.31-2.436.60.3792.10.379197.3
2.43-2.586.60.233.40.231100
2.58-2.766.30.1425.50.1421100
2.76-2.986.50.0779.80.077199.9
2.98-3.276.60.04615.40.046199.9
3.27-3.656.10.032200.032199.9
3.65-4.226.40.02326.70.0231100
4.22-5.166.10.01928.90.019199.8
5.16-7.360.0228.60.02199.9
7.3-34.8275.30.01536.10.015198.9

-
Phasing

PhasingMethod: molecular replacement

-
Processing

Software
NameVersionClassificationNB
SCALA3.3.20data scaling
PHASERphasing
REFMACrefinement
PDB_EXTRACT3.11data extraction
Blu-Icedata collection
autoXDSdata reduction
RefinementMethod to determine structure: MOLECULAR REPLACEMENT / Resolution: 2.31→34.85 Å / Cor.coef. Fo:Fc: 0.971 / Cor.coef. Fo:Fc free: 0.954 / Occupancy max: 1 / Occupancy min: 0.5 / SU B: 7.134 / SU ML: 0.17 / SU R Cruickshank DPI: 0.0609 / Cross valid method: THROUGHOUT / ESU R: 0.283 / ESU R Free: 0.218 / Stereochemistry target values: MAXIMUM LIKELIHOOD / Details: HYDROGENS HAVE BEEN ADDED IN THE RIDING POSITIONS
RfactorNum. reflection% reflectionSelection details
Rfree0.234 512 4.8 %RANDOM
Rwork0.18513 ---
obs0.18753 10128 99.29 %-
Solvent computationIon probe radii: 0.8 Å / Shrinkage radii: 0.8 Å / VDW probe radii: 1.2 Å / Solvent model: MASK
Displacement parametersBiso mean: 71.019 Å2
Baniso -1Baniso -2Baniso -3
1--0.06 Å20 Å2-0 Å2
2---0.06 Å20 Å2
3---0.12 Å2
Refinement stepCycle: LAST / Resolution: 2.31→34.85 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms1500 0 70 20 1590
Refine LS restraints
Refine-IDTypeDev idealDev ideal targetNumber
X-RAY DIFFRACTIONr_bond_refined_d0.0150.0191594
X-RAY DIFFRACTIONr_bond_other_d0.0010.021656
X-RAY DIFFRACTIONr_angle_refined_deg1.9522.0422153
X-RAY DIFFRACTIONr_angle_other_deg0.84133806
X-RAY DIFFRACTIONr_dihedral_angle_1_deg7.0545196
X-RAY DIFFRACTIONr_dihedral_angle_2_deg40.7392552
X-RAY DIFFRACTIONr_dihedral_angle_3_deg14.98815286
X-RAY DIFFRACTIONr_dihedral_angle_4_deg14.808158
X-RAY DIFFRACTIONr_chiral_restr0.1070.2260
X-RAY DIFFRACTIONr_gen_planes_refined0.0080.0211744
X-RAY DIFFRACTIONr_gen_planes_other0.0020.02334
X-RAY DIFFRACTIONr_nbd_refined
X-RAY DIFFRACTIONr_nbd_other
X-RAY DIFFRACTIONr_nbtor_refined
X-RAY DIFFRACTIONr_nbtor_other
X-RAY DIFFRACTIONr_xyhbond_nbd_refined
X-RAY DIFFRACTIONr_xyhbond_nbd_other
X-RAY DIFFRACTIONr_metal_ion_refined
X-RAY DIFFRACTIONr_metal_ion_other
X-RAY DIFFRACTIONr_symmetry_vdw_refined
X-RAY DIFFRACTIONr_symmetry_vdw_other
X-RAY DIFFRACTIONr_symmetry_hbond_refined
X-RAY DIFFRACTIONr_symmetry_hbond_other
X-RAY DIFFRACTIONr_symmetry_metal_ion_refined
X-RAY DIFFRACTIONr_symmetry_metal_ion_other
X-RAY DIFFRACTIONr_mcbond_it4.9376.116791
X-RAY DIFFRACTIONr_mcbond_other4.9316.114790
X-RAY DIFFRACTIONr_mcangle_it6.329.135984
X-RAY DIFFRACTIONr_mcangle_other
X-RAY DIFFRACTIONr_scbond_it5.7116.693801
X-RAY DIFFRACTIONr_scbond_other
X-RAY DIFFRACTIONr_scangle_it
X-RAY DIFFRACTIONr_scangle_other
X-RAY DIFFRACTIONr_long_range_B_refined
X-RAY DIFFRACTIONr_long_range_B_other
X-RAY DIFFRACTIONr_rigid_bond_restr
X-RAY DIFFRACTIONr_sphericity_free
X-RAY DIFFRACTIONr_sphericity_bonded
LS refinement shellResolution: 2.311→2.371 Å / Total num. of bins used: 20
RfactorNum. reflection% reflection
Rfree0.274 40 -
Rwork0.229 705 -
obs--97.13 %
Refinement TLS params.

Method: refined / Refine-ID: X-RAY DIFFRACTION

IDL11 (°2)L12 (°2)L13 (°2)L22 (°2)L23 (°2)L33 (°2)S11 (Å °)S12 (Å °)S13 (Å °)S21 (Å °)S22 (Å °)S23 (Å °)S31 (Å °)S32 (Å °)S33 (Å °)T11 (Å2)T12 (Å2)T13 (Å2)T22 (Å2)T23 (Å2)T33 (Å2)Origin x (Å)Origin y (Å)Origin z (Å)
10.85310.5597-0.21811.88460.20950.51160.11070.1419-0.1076-0.029-0.1650.1661-0.1096-0.07450.05430.03840.0284-0.04550.0705-0.04920.0991-24.1354-7.2901-31.6221
21.3655-0.04060.58540.9660.57461.26760.0596-0.0260.10050.012-0.0478-0.0249-0.0369-0.0411-0.01180.042-0.02210.00280.01630.00580.0318-9.84075.6176-20.2526
Refinement TLS group
IDRefine-IDRefine TLS-IDAuth asym-IDAuth seq-ID
1X-RAY DIFFRACTION1A1 - 99
2X-RAY DIFFRACTION2B1 - 99

+
About Yorodumi

-
News

-
Feb 9, 2022. New format data for meta-information of EMDB entries

New format data for meta-information of EMDB entries

  • Version 3 of the EMDB header file is now the official format.
  • The previous official version 1.9 will be removed from the archive.

Related info.:EMDB header

External links:wwPDB to switch to version 3 of the EMDB data model

-
Aug 12, 2020. Covid-19 info

Covid-19 info

URL: https://pdbjlvh1.pdbj.org/emnavi/covid19.php

New page: Covid-19 featured information page in EM Navigator.

Related info.:Covid-19 info / Mar 5, 2020. Novel coronavirus structure data

+
Mar 5, 2020. Novel coronavirus structure data

Novel coronavirus structure data

Related info.:Yorodumi Speices / Aug 12, 2020. Covid-19 info

External links:COVID-19 featured content - PDBj / Molecule of the Month (242)：Coronavirus Proteases

+
Jan 31, 2019. EMDB accession codes are about to change! (news from PDBe EMDB page)

EMDB accession codes are about to change! (news from PDBe EMDB page)

  • The allocation of 4 digits for EMDB accession codes will soon come to an end. Whilst these codes will remain in use, new EMDB accession codes will include an additional digit and will expand incrementally as the available range of codes is exhausted. The current 4-digit format prefixed with “EMD-” (i.e. EMD-XXXX) will advance to a 5-digit format (i.e. EMD-XXXXX), and so on. It is currently estimated that the 4-digit codes will be depleted around Spring 2019, at which point the 5-digit format will come into force.
  • The EM Navigator/Yorodumi systems omit the EMD- prefix.

Related info.:Q: What is EMD? / ID/Accession-code notation in Yorodumi/EM Navigator

External links:EMDB Accession Codes are Changing Soon! / Contact to PDBj

+
Jul 12, 2017. Major update of PDB

Major update of PDB

  • wwPDB released updated PDB data conforming to the new PDBx/mmCIF dictionary.
  • This is a major update changing the version number from 4 to 5, and with Remediation, in which all the entries are updated.
  • In this update, many items about electron microscopy experimental information are reorganized (e.g. em_software).
  • Now, EM Navigator and Yorodumi are based on the updated data.

External links:wwPDB Remediation / Enriched Model Files Conforming to OneDep Data Standards Now Available in the PDB FTP Archive

-
Yorodumi

Thousand views of thousand structures

  • Yorodumi is a browser for structure data from EMDB, PDB, SASBDB, etc.
  • This page is also the successor to EM Navigator detail page, and also detail information page/front-end page for Omokage search.
  • The word "yorodu" (or yorozu) is an old Japanese word meaning "ten thousand". "mi" (miru) is to see.

Related info.:EMDB / PDB / SASBDB / Comparison of 3 databanks / Yorodumi Search / Aug 31, 2016. New EM Navigator & Yorodumi / Yorodumi Papers / Jmol/JSmol / Function and homology information / Changes in new EM Navigator and Yorodumi

Read more