[English] 日本語
Yorodumi
- PDB-7klk: Human Arginase1 Complexed with Inhibitor Compound 3a -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 7klk
TitleHuman Arginase1 Complexed with Inhibitor Compound 3a
ComponentsArginase-1
KeywordsHYDROLASE/INHIBITOR / Arginase / hydrolase / urea cycle / metabolism / 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 / arginase / arginine catabolic process to ornithine / 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 / arginase / arginine catabolic process to ornithine / 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
Arginase / Ureohydrolase, manganese-binding site / Arginase family signature. / Ureohydrolase / Arginase family / Arginase family profile. / Ureohydrolase domain superfamily
Similarity search - Domain/homology
: / Chem-XFP / Arginase-1
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 1.801 Å
AuthorsPalte, R.L.
CitationJournal: Acs Med.Chem.Lett. / Year: 2021
Title: Structure-Based Discovery of Proline-Derived Arginase Inhibitors with Improved Oral Bioavailability for Immuno-Oncology.
Authors: Lu, M. / Zhang, H. / Li, D. / Childers, M. / Pu, Q. / Palte, R.L. / Gathiaka, S. / Lyons, T.W. / Palani, A. / Fan, P.W. / Spacciapoli, P. / Miller, J.R. / Cho, H. / Cheng, M. / Chakravarthy, ...Authors: Lu, M. / Zhang, H. / Li, D. / Childers, M. / Pu, Q. / Palte, R.L. / Gathiaka, S. / Lyons, T.W. / Palani, A. / Fan, P.W. / Spacciapoli, P. / Miller, J.R. / Cho, H. / Cheng, M. / Chakravarthy, K. / O'Neil, J. / Eangoor, P. / Beard, A. / Kim, H.Y. / Sauri, J. / Gunaydin, H. / Sloman, D.L. / Siliphaivanh, P. / Cumming, J. / Fischer, C.
History
DepositionOct 30, 2020Deposition site: RCSB / Processing site: RCSB
Revision 1.0Sep 29, 2021Provider: repository / Type: Initial release
Revision 1.1Oct 18, 2023Group: Data collection / Refinement description
Category: chem_comp_atom / chem_comp_bond / pdbx_initial_refinement_model

-
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)210,79325
Polymers208,6796
Non-polymers2,11419
Water19,0961060
1
A: Arginase-1
B: Arginase-1
E: Arginase-1
hetero molecules


Theoretical massNumber of molelcules
Total (without water)105,36512
Polymers104,3403
Non-polymers1,0269
Water543
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
MethodPISA
2
C: Arginase-1
D: Arginase-1
F: Arginase-1
hetero molecules


Theoretical massNumber of molelcules
Total (without water)105,42813
Polymers104,3403
Non-polymers1,08810
Water543
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
MethodPISA
Unit cell
Length a, b, c (Å)53.157, 281.463, 67.078
Angle α, β, γ (deg.)90.000, 90.060, 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 / 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-XFP / 3-[(2~{S},3~{R})-2-carboxypiperidin-3-yl]propyl-$l^{3}-oxidanyl-bis(oxidanyl)boranuide


Mass: 232.062 Da / Num. of mol.: 6 / Source method: obtained synthetically / Formula: C9H19BNO5 / Feature type: SUBJECT OF INVESTIGATION
#4: Chemical ChemComp-EDO / 1,2-ETHANEDIOL / ETHYLENE GLYCOL


Mass: 62.068 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C2H6O2
#5: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 1060 / 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: 2.4 Å3/Da / Density % sol: 48.85 %
Crystal growTemperature: 293 K / Method: vapor diffusion, hanging drop / 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: Mar 10, 2017
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 1 Å / Relative weight: 1
ReflectionResolution: 1.8→67.08 Å / Num. obs: 179355 / % possible obs: 99.2 % / Redundancy: 3.4 % / CC1/2: 0.996 / Net I/σ(I): 13
Reflection shellResolution: 1.8→1.9 Å / Num. unique obs: 25947 / CC1/2: 0.916

-
Processing

Software
NameVersionClassification
BUSTER2.11.7 (20-MAY-2020)refinement
PDB_EXTRACT3.25data extraction
XDSdata reduction
AutoProcessdata scaling
autoBUSTERphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: 6V7C

6v7c


Resolution: 1.801→67.08 Å / Cor.coef. Fo:Fc: 0.89 / Cor.coef. Fo:Fc free: 0.864 / SU R Cruickshank DPI: 0.135 / Cross valid method: THROUGHOUT / σ(F): 0 / SU R Blow DPI: 0.134 / SU Rfree Blow DPI: 0.125 / SU Rfree Cruickshank DPI: 0.126
RfactorNum. reflection% reflectionSelection details
Rfree0.2365 8908 4.97 %RANDOM
Rwork0.2045 ---
obs0.206 179276 99.2 %-
Displacement parametersBiso max: 87.54 Å2 / Biso mean: 16.67 Å2 / Biso min: 3 Å2
Baniso -1Baniso -2Baniso -3
1-1.4855 Å20 Å22.0172 Å2
2---4.9788 Å20 Å2
3---3.4933 Å2
Refine analyzeLuzzati coordinate error obs: 0.27 Å
Refinement stepCycle: final / Resolution: 1.801→67.08 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms14473 0 112 1060 15645
Biso mean--16.03 22.9 -
Num. residues----1905
Refine LS restraints
Refine-IDTypeNumberRestraint functionWeightDev ideal
X-RAY DIFFRACTIONt_dihedral_angle_d5150SINUSOIDAL2
X-RAY DIFFRACTIONt_trig_c_planes
X-RAY DIFFRACTIONt_gen_planes2463HARMONIC5
X-RAY DIFFRACTIONt_it14875HARMONIC10
X-RAY DIFFRACTIONt_nbd
X-RAY DIFFRACTIONt_improper_torsion
X-RAY DIFFRACTIONt_pseud_angle
X-RAY DIFFRACTIONt_chiral_improper_torsion1959SEMIHARMONIC5
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_contact13860SEMIHARMONIC4
X-RAY DIFFRACTIONt_bond_d14875HARMONIC20.008
X-RAY DIFFRACTIONt_angle_deg20184HARMONIC21.01
X-RAY DIFFRACTIONt_omega_torsion3.59
X-RAY DIFFRACTIONt_other_torsion15.57
LS refinement shellResolution: 1.801→1.81 Å / Rfactor Rfree error: 0
RfactorNum. reflection% reflection
Rfree0.2936 181 5.05 %
Rwork0.2379 3405 -
obs--84.93 %

+
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