[English] 日本語
Yorodumi
- PDB-7k6u: Carbonic Anhydrase IX mimic complexed with 4-(2-(3-(4-methylpheny... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 7k6u
TitleCarbonic Anhydrase IX mimic complexed with 4-(2-(3-(4-methylphenyl)ureido)ethylsulfonamido)benzenesulfonamide
ComponentsCarbonic anhydrase 2
KeywordsLYASE/LYASE INHIBITOR / Carbonic Anhydrase / CAII / CAIX inhibitor / Structure guided drug design / Structure activity relationship study / Breast Cancer / LYASE / LYASE-LYASE INHIBITOR complex
Function / homology
Function and homology information


positive regulation of cellular pH reduction / positive regulation of dipeptide transmembrane transport / regulation of monoatomic anion transport / secretion / cyanamide hydratase activity / cyanamide hydratase / arylesterase activity / regulation of chloride transport / Reversible hydration of carbon dioxide / morphogenesis of an epithelium ...positive regulation of cellular pH reduction / positive regulation of dipeptide transmembrane transport / regulation of monoatomic anion transport / secretion / cyanamide hydratase activity / cyanamide hydratase / arylesterase activity / regulation of chloride transport / Reversible hydration of carbon dioxide / morphogenesis of an epithelium / angiotensin-activated signaling pathway / regulation of intracellular pH / positive regulation of synaptic transmission, GABAergic / carbonic anhydrase / carbonate dehydratase activity / carbon dioxide transport / Erythrocytes take up oxygen and release carbon dioxide / Erythrocytes take up carbon dioxide and release oxygen / neuron cellular homeostasis / apical part of cell / myelin sheath / extracellular exosome / zinc ion binding / plasma membrane / cytosol / cytoplasm
Similarity search - Function
Carbonic anhydrase, alpha-class, conserved site / Alpha-carbonic anhydrases signature. / Carbonic anhydrase, alpha-class / Alpha carbonic anhydrase domain / Alpha carbonic anhydrase domain superfamily / Eukaryotic-type carbonic anhydrase / Alpha-carbonic anhydrases profile. / Eukaryotic-type carbonic anhydrase
Similarity search - Domain/homology
Chem-VYY / Carbonic anhydrase 2
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 1.605 Å
AuthorsAndring, J.T. / Singh, S. / McKenna, R.
CitationJournal: Eur.J.Med.Chem. / Year: 2021
Title: Handling drug-target selectivity: A study on ureido containing Carbonic Anhydrase inhibitors.
Authors: Akgul, O. / Singh, S. / Andring, J.T. / McKenna, R. / Selleri, S. / Carta, F. / Angeli, A. / Supuran, C.T.
History
DepositionSep 21, 2020Deposition site: RCSB / Processing site: RCSB
Revision 1.0Dec 23, 2020Provider: repository / Type: Initial release
Revision 1.1Feb 24, 2021Group: Database references / Category: citation / Item: _citation.journal_volume / _citation.year
Revision 1.2Oct 18, 2023Group: Data collection / Database references / Refinement description
Category: chem_comp_atom / chem_comp_bond ...chem_comp_atom / chem_comp_bond / database_2 / pdbx_initial_refinement_model
Item: _database_2.pdbx_DOI / _database_2.pdbx_database_accession

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: Carbonic anhydrase 2
hetero molecules


Theoretical massNumber of molelcules
Total (without water)29,7574
Polymers29,2011
Non-polymers5563
Water2,612145
1


  • Idetical with deposited unit
  • defined by author
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area240 Å2
ΔGint4 kcal/mol
Surface area11460 Å2
Unit cell
Length a, b, c (Å)41.991, 41.293, 72.047
Angle α, β, γ (deg.)90.000, 103.850, 90.000
Int Tables number4
Space group name H-MP1211

-
Components

#1: Protein Carbonic anhydrase 2 / Carbonate dehydratase II / Carbonic anhydrase C / CAC / Carbonic anhydrase II / CA-II


Mass: 29200.887 Da / Num. of mol.: 1 / Mutation: A65S, N67Q, E69T, I91L, F131V, K170E, L204A
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: CA2 / Production host: Escherichia coli (E. coli) / References: UniProt: P00918, carbonic anhydrase
#2: Chemical ChemComp-ZN / ZINC ION


Mass: 65.409 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: Zn
#3: Chemical ChemComp-VYY / 4-{[(2-{[(4-methylphenyl)carbamoyl]amino}ethyl)sulfonyl]amino}benzene-1-sulfonamide


Mass: 412.484 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C16H20N4O5S2 / Feature type: SUBJECT OF INVESTIGATION
#4: Chemical ChemComp-DMS / DIMETHYL SULFOXIDE


Mass: 78.133 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C2H6OS / Comment: DMSO, precipitant*YM
#5: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 145 / 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: 2.1 Å3/Da / Density % sol: 41.5 %
Crystal growTemperature: 295 K / Method: vapor diffusion, hanging drop / pH: 6.4 / Details: 1.6M Sodium Citrate, 50mM Tris, pH 6.4

-
Data collection

DiffractionMean temperature: 100 K / Serial crystal experiment: N
Diffraction sourceSource: SYNCHROTRON / Site: CHESS / Beamline: F1 / Wavelength: 0.9177 Å
DetectorType: DECTRIS PILATUS 6M / Detector: PIXEL / Date: May 1, 2018
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.9177 Å / Relative weight: 1
ReflectionResolution: 1.605→32.05 Å / Num. obs: 31486 / % possible obs: 99.6 % / Redundancy: 3.3 % / Biso Wilson estimate: 15 Å2 / CC1/2: 0.998 / Rmerge(I) obs: 0.059 / Rpim(I) all: 0.038 / Rrim(I) all: 0.071 / Net I/σ(I): 13
Reflection shell

Diffraction-ID: 1 / Redundancy: 3.2 %

Resolution (Å)Rmerge(I) obsNum. measured allNum. unique obsCC1/2Rpim(I) allRrim(I) allNet I/σ(I) obs% possible all
1.61-1.630.515488615260.7740.3360.6172.397.3
8.79-32.050.0276602080.9990.0170.03235.695.3

-
Processing

Software
NameVersionClassification
PHENIX1.10pre_2097refinement
Aimless0.7.4data scaling
PDB_EXTRACT3.25data extraction
XDSdata reduction
PHENIXphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: 3ks3

3ks3


Resolution: 1.605→23.318 Å / SU ML: 0.16 / Cross valid method: THROUGHOUT / σ(F): 1.34 / Phase error: 19.53 / Stereochemistry target values: ML
RfactorNum. reflection% reflection
Rfree0.1961 1572 5 %
Rwork0.1776 29894 -
obs0.1786 31466 99.62 %
Solvent computationShrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å / Solvent model: FLAT BULK SOLVENT MODEL
Displacement parametersBiso max: 82.23 Å2 / Biso mean: 20.0873 Å2 / Biso min: 6.92 Å2
Refinement stepCycle: final / Resolution: 1.605→23.318 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms2042 0 32 145 2219
Biso mean--27.68 26.73 -
Num. residues----257
Refine LS restraints
Refine-IDTypeDev idealNumber
X-RAY DIFFRACTIONf_bond_d0.0122151
X-RAY DIFFRACTIONf_angle_d1.4272923
X-RAY DIFFRACTIONf_chiral_restr0.296302
X-RAY DIFFRACTIONf_plane_restr0.012378
X-RAY DIFFRACTIONf_dihedral_angle_d14.522779
LS refinement shell

Refine-ID: X-RAY DIFFRACTION / Rfactor Rfree error: 0

Resolution (Å)Rfactor RfreeNum. reflection RfreeRfactor RworkNum. reflection Rwork% reflection obs (%)
1.6054-1.65720.28321510.2551265498
1.6572-1.71640.23831310.22382705100
1.7164-1.78510.21381420.19612702100
1.7851-1.86640.24441310.18412709100
1.8664-1.96470.19091520.18342721100
1.9647-2.08770.2151540.17782687100
2.0877-2.24880.22491250.17782735100
2.2488-2.47490.20861490.18192710100
2.4749-2.83250.21541620.19082703100
2.8325-3.56660.19151250.17612760100
3.5666-23.3180.13961500.147280899
Refinement TLS params.Method: refined / Origin x: -5.3797 Å / Origin y: -1.7449 Å / Origin z: 86.0329 Å
111213212223313233
T0.0045 Å20.0076 Å2-0.0009 Å2-0.0033 Å20.0029 Å2--0.0136 Å2
L0.023 °20.0082 °2-0.0024 °2-0.032 °2-0.0163 °2--0.0282 °2
S-0.028 Å °-0.0791 Å °0.067 Å °-0.1085 Å °0.0938 Å °-0.0224 Å °0.0525 Å °0.0366 Å °-0 Å °
Refinement TLS group
IDRefine-IDRefine TLS-IDSelection detailsAuth asym-IDAuth seq-ID
1X-RAY DIFFRACTION1allA4 - 261
2X-RAY DIFFRACTION1allB1 - 43
3X-RAY DIFFRACTION1allB45 - 76
4X-RAY DIFFRACTION1allB77 - 128
5X-RAY DIFFRACTION1allB135 - 177
6X-RAY DIFFRACTION1allB178 - 187
7X-RAY DIFFRACTION1allC262
8X-RAY DIFFRACTION1allD1
9X-RAY DIFFRACTION1allE1

+
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