[English] 日本語
Yorodumi
- PDB-6v7f: Human Arginase1 Complexed with Bicyclic Inhibitor Compound 13 -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 6v7f
TitleHuman Arginase1 Complexed with Bicyclic Inhibitor Compound 13
ComponentsArginase-1
KeywordsHYDROLASE/HYDROLASE INHIBITOR / AGONIST / ARG (ARGINASE) / BICYCLIC / IMMUNOTHERAPY / METALLOENZYME / HYDROLASE / HYDROLASE-HYDROLASE INHIBITOR complex
Function / homology
Function and homology information


positive regulation of neutrophil mediated killing of fungus / Urea cycle / negative regulation of T-helper 2 cell cytokine production / arginine catabolic process to ornithine / arginase / arginase activity / urea cycle / negative regulation of type II interferon-mediated signaling pathway / defense response to protozoan / negative regulation of activated T cell proliferation ...positive regulation of neutrophil mediated killing of fungus / Urea cycle / negative regulation of T-helper 2 cell cytokine production / arginine catabolic process to ornithine / arginase / arginase activity / urea cycle / negative regulation of type II interferon-mediated signaling pathway / defense response to protozoan / negative regulation of activated T cell proliferation / arginine catabolic process / negative regulation of T cell proliferation / specific granule lumen / azurophil granule lumen / manganese ion binding / adaptive immune response / innate immune response / Neutrophil degranulation / extracellular space / extracellular region / nucleus / cytosol / cytoplasm
Similarity search - Function
Ureohydrolase domain / Arginase / Ureohydrolase, manganese-binding site / Arginase family signature. / Ureohydrolase / Arginase family / Arginase family profile. / Arginase; Chain A / Ureohydrolase domain superfamily / 3-Layer(aba) Sandwich / Alpha Beta
Similarity search - Domain/homology
: / Chem-QRJ / Arginase-1
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.02 Å
AuthorsPalte, R.L. / Lesburg, C.A.
CitationJournal: Acs Med.Chem.Lett. / Year: 2020
Title: Discovery and Optimization of Rationally Designed Bicyclic Inhibitors of Human Arginase to Enhance Cancer Immunotherapy.
Authors: Mitcheltree, M.J. / Li, D. / Achab, A. / Beard, A. / Chakravarthy, K. / Cheng, M. / Cho, H. / Eangoor, P. / Fan, P. / Gathiaka, S. / Kim, H.Y. / Lesburg, C.A. / Lyons, T.W. / Martinot, T.A. ...Authors: Mitcheltree, M.J. / Li, D. / Achab, A. / Beard, A. / Chakravarthy, K. / Cheng, M. / Cho, H. / Eangoor, P. / Fan, P. / Gathiaka, S. / Kim, H.Y. / Lesburg, C.A. / Lyons, T.W. / Martinot, T.A. / Miller, J.R. / McMinn, S. / O'Neil, J. / Palani, A. / Palte, R.L. / Sauri, J. / Sloman, D.L. / Zhang, H. / Cumming, J.N. / Fischer, C.
History
DepositionDec 8, 2019Deposition site: RCSB / Processing site: RCSB
Revision 1.0May 6, 2020Provider: repository / Type: Initial release
Revision 1.1Oct 11, 2023Group: Data collection / Database references ...Data collection / Database references / Derived calculations / Refinement description
Category: chem_comp_atom / chem_comp_bond ...chem_comp_atom / chem_comp_bond / database_2 / pdbx_initial_refinement_model / software / struct_conn
Item: _database_2.pdbx_DOI / _database_2.pdbx_database_accession ..._database_2.pdbx_DOI / _database_2.pdbx_database_accession / _software.name / _struct_conn.pdbx_dist_value / _struct_conn.ptnr1_auth_asym_id / _struct_conn.ptnr1_auth_comp_id / _struct_conn.ptnr1_auth_seq_id / _struct_conn.ptnr1_label_asym_id / _struct_conn.ptnr1_label_atom_id / _struct_conn.ptnr1_label_comp_id / _struct_conn.ptnr1_label_seq_id / _struct_conn.ptnr2_auth_asym_id / _struct_conn.ptnr2_auth_comp_id / _struct_conn.ptnr2_auth_seq_id / _struct_conn.ptnr2_label_asym_id / _struct_conn.ptnr2_label_atom_id / _struct_conn.ptnr2_label_comp_id

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: Arginase-1
B: Arginase-1
C: Arginase-1
D: Arginase-1
E: Arginase-1
F: Arginase-1
hetero molecules


Theoretical massNumber of molelcules
Total (without water)211,07324
Polymers208,6796
Non-polymers2,39418
Water14,520806
1
A: Arginase-1
B: Arginase-1
E: Arginase-1
hetero molecules


Theoretical massNumber of molelcules
Total (without water)105,53712
Polymers104,3403
Non-polymers1,1979
Water543
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area5770 Å2
ΔGint-16 kcal/mol
Surface area33420 Å2
MethodPISA
2
C: Arginase-1
D: Arginase-1
F: Arginase-1
hetero molecules


Theoretical massNumber of molelcules
Total (without water)105,53712
Polymers104,3403
Non-polymers1,1979
Water543
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area5700 Å2
ΔGint-14 kcal/mol
Surface area33400 Å2
MethodPISA
Unit cell
Length a, b, c (Å)53.510, 285.560, 67.160
Angle α, β, γ (deg.)90.000, 90.040, 90.000
Int Tables number4
Space group name H-MP1211

-
Components

#1: Protein
Arginase-1 / / Liver-type arginase / Type I arginase


Mass: 34779.879 Da / Num. of mol.: 6
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: ARG1 / Plasmid: pET24 / Cell (production host): BL21 / Production host: Escherichia coli BL21 (bacteria) / References: UniProt: P05089, arginase
#2: Chemical
ChemComp-MN / MANGANESE (II) ION


Mass: 54.938 Da / Num. of mol.: 12 / Source method: obtained synthetically / Formula: Mn
#3: Chemical
ChemComp-QRJ / {3-[(5R,7S,8S)-8-azaniumyl-8-carboxy-2-azaspiro[4.4]nonan-2-ium-7-yl]propyl}(trihydroxy)borate(1-)


Mass: 289.156 Da / Num. of mol.: 6 / Source method: obtained synthetically / Formula: C12H26BN2O5
#4: Water ChemComp-HOH / water / Water


Mass: 18.015 Da / Num. of mol.: 806 / Source method: isolated from a natural source / Formula: H2O
Has ligand of interestY

-
Experimental details

-
Experiment

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

-
Sample preparation

CrystalDensity Matthews: 2.46 Å3/Da / Density % sol: 49.98 %
Crystal growTemperature: 293 K / Method: vapor diffusion / pH: 7
Details: 10% MMT (pH 7.0) 0.1 M ammonium formate, 16-22% PEG 8000

-
Data collection

DiffractionMean temperature: 100 K / Serial crystal experiment: N
Diffraction sourceSource: SYNCHROTRON / Site: APS / Beamline: 17-ID / Wavelength: 1 Å
DetectorType: DECTRIS PILATUS 6M / Detector: PIXEL / Date: Dec 15, 2017
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 1 Å / Relative weight: 1
ReflectionResolution: 2.02→47.59 Å / Num. obs: 121309 / % possible obs: 93 % / Redundancy: 3.1 % / CC1/2: 0.97 / Rmerge(I) obs: 0.17 / Net I/σ(I): 5.1
Reflection shellResolution: 2.02→2.06 Å / Rmerge(I) obs: 0.49 / Mean I/σ(I) obs: 2.1 / Num. unique obs: 5351 / CC1/2: 0.73

-
Processing

Software
NameVersionClassification
BUSTER2.11.7refinement
PDB_EXTRACT3.25data extraction
XDSdata reduction
autoPROCdata scaling
autoBUSTERphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: 6V7C

6v7c


Resolution: 2.02→47.59 Å / Cor.coef. Fo:Fc: 0.751 / Cor.coef. Fo:Fc free: 0.699 / SU R Cruickshank DPI: 0.243 / Cross valid method: THROUGHOUT / σ(F): 0 / SU R Blow DPI: 0.238 / SU Rfree Blow DPI: 0.187 / SU Rfree Cruickshank DPI: 0.191
RfactorNum. reflection% reflectionSelection details
Rfree0.258 6023 4.97 %RANDOM
Rwork0.23 ---
obs0.231 121305 92.5 %-
Displacement parametersBiso max: 116.99 Å2 / Biso mean: 15.95 Å2 / Biso min: 3 Å2
Baniso -1Baniso -2Baniso -3
1-5.7154 Å20 Å2-1.4479 Å2
2---13.8544 Å20 Å2
3---8.139 Å2
Refine analyzeLuzzati coordinate error obs: 0.37 Å
Refinement stepCycle: final / Resolution: 2.02→47.59 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms14511 0 132 806 15449
Biso mean--13.26 11.55 -
Num. residues----1911
Refine LS restraints
Refine-IDTypeNumberRestraint functionWeightDev ideal
X-RAY DIFFRACTIONt_dihedral_angle_d5205SINUSOIDAL2
X-RAY DIFFRACTIONt_trig_c_planes312HARMONIC2
X-RAY DIFFRACTIONt_gen_planes2169HARMONIC5
X-RAY DIFFRACTIONt_it14982HARMONIC20
X-RAY DIFFRACTIONt_nbd5SEMIHARMONIC5
X-RAY DIFFRACTIONt_improper_torsion
X-RAY DIFFRACTIONt_pseud_angle
X-RAY DIFFRACTIONt_chiral_improper_torsion1971SEMIHARMONIC5
X-RAY DIFFRACTIONt_sum_occupancies
X-RAY DIFFRACTIONt_utility_distance
X-RAY DIFFRACTIONt_utility_angle
X-RAY DIFFRACTIONt_utility_torsion
X-RAY DIFFRACTIONt_ideal_dist_contact18468SEMIHARMONIC4
X-RAY DIFFRACTIONt_bond_d14982HARMONIC20.009
X-RAY DIFFRACTIONt_angle_deg20366HARMONIC21.11
X-RAY DIFFRACTIONt_omega_torsion2.94
X-RAY DIFFRACTIONt_other_torsion16.19
LS refinement shellResolution: 2.02→2.07 Å / Rfactor Rfree error: 0 / Total num. of bins used: 20
RfactorNum. reflection% reflection
Rfree0.2601 376 5.08 %
Rwork0.246 7031 -
all0.2467 7407 -
obs--76.09 %
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)
10.22870.0554-0.1690.00840.18780.3254-0.01030.06180.00320.02170.0086-0.05940-0.03910.0018-0.0662-0.00010.0041-0.07-0.0458-0.023513.2004-1.321210.5633
20.26330.0583-0.31400.10220.3047-0.0023-0.01430.0117-0.00580.0072-0.01350.0111-0.0338-0.0049-0.0838-0.0078-0.0013-0.0156-0.0335-0.0349-10.9161-5.087543.18
30.2676-0.06280.36170.1998-0.10520.1284-0.0013-0.0703-0.0164-0.02030.0062-0.027-0.0263-0.0163-0.0049-0.06990.01-0.0084-0.0679-0.0588-0.0142-13.51442.391520.7876
40.0279-0.17830.35680.04560.10420.29410.00570.05350.00620.017-0.00410.01090.0031-0.0065-0.0016-0.0860.0143-0.0252-0.0326-0.0358-0.0109-37.646346.3729-11.9361
50.0360.15530.02060.3499-0.00120.0520.00130.0218-0.0468-0.00230.0037-0.02550.0555-0.036-0.0049-0.014-0.04150.0122-0.0652-0.0507-0.0211-7.6615-35.945916.6209
60.0619-0.0982-0.11210.1476-0.06030.0751-0.00160.02080.03150.02520.0113-0.041-0.0587-0.039-0.0097-0.00670.0438-0.0127-0.0931-0.04690.0032-34.435577.06214.7103
Refinement TLS group
IDRefine-IDRefine TLS-IDSelection detailsAuth asym-IDAuth seq-ID
1X-RAY DIFFRACTION1{ A|* }A2 - 319
2X-RAY DIFFRACTION2{ B|* }B2 - 320
3X-RAY DIFFRACTION3{ C|* }C2 - 319
4X-RAY DIFFRACTION4{ D|* }D2 - 319
5X-RAY DIFFRACTION5{ E|* }E2 - 320
6X-RAY DIFFRACTION6{ F|* }F2 - 320

+
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://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