[English] 日本語
Yorodumi
- PDB-8eyl: Human Carbonic Anhydrase II with Tert-butyl (2-(2-((2-(2,6-dioxop... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 8eyl
TitleHuman Carbonic Anhydrase II with Tert-butyl (2-(2-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)amino)ethoxy)ethyl)carbamate
ComponentsCarbonic anhydrase 2
KeywordsLYASE / targeted protein degrader / PROTAC / metalloenzyme
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 / positive regulation of synaptic transmission, GABAergic / regulation of intracellular pH / 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 / cytoplasm / cytosol
Similarity search - Function
Carbonic Anhydrase II / Alpha carbonic anhydrase / 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 ...Carbonic Anhydrase II / Alpha carbonic anhydrase / 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 / Roll / Alpha Beta
Similarity search - Domain/homology
MERCURIBENZOIC ACID / Chem-X5F / Carbonic anhydrase 2
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 1.18 Å
AuthorsKohlbrand, A.J. / O'Herin, C.B.
Funding support United States, 1items
OrganizationGrant numberCountry
National Institutes of Health/National Institute Of Allergy and Infectious Diseases (NIH/NIAID) United States
CitationJournal: J.Med.Chem. / Year: 2023
Title: Development of Human Carbonic Anhydrase II Heterobifunctional Degraders.
Authors: O'Herin, C.B. / Moriuchi, Y.W. / Bemis, T.A. / Kohlbrand, A.J. / Burkart, M.D. / Cohen, S.M.
History
DepositionOct 27, 2022Deposition site: RCSB / Processing site: RCSB
Revision 1.0Feb 22, 2023Provider: repository / Type: Initial release
Revision 1.1Oct 25, 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: Carbonic anhydrase 2
hetero molecules


Theoretical massNumber of molelcules
Total (without water)30,8355
Polymers29,2891
Non-polymers1,5464
Water3,945219
1


  • Idetical with deposited unit
  • defined by author
  • Evidence: gel filtration
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Unit cell
Length a, b, c (Å)41.872, 41.036, 71.269
Angle α, β, γ (deg.)90.000, 103.954, 90.000
Int Tables number4
Space group name H-MP1211
Space group name HallP2yb
Symmetry operation#1: x,y,z
#2: -x,y+1/2,-z

-
Components

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


Mass: 29289.062 Da / Num. of mol.: 1
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-MBO / MERCURIBENZOIC ACID


Mass: 321.703 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C7H5HgO2
#4: Chemical ChemComp-X5F / 2-[[(2~{R})-1-azanyl-5-oxidanyl-1,5-bis(oxidanylidene)pentan-2-yl]carbamoyl]-6-[2-[2-[(4-sulfamoylphenyl)carbonylamino]ethoxy]ethylamino]benzoic acid


Mass: 579.580 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: C24H29N5O10S / Feature type: SUBJECT OF INVESTIGATION
#5: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 219 / 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: 2.03 Å3/Da / Density % sol: 39.37 %
Crystal growTemperature: 293 K / Method: vapor diffusion, hanging drop
Details: 2.6-3.0 M Ammonium sulfate in 50 mM Tris-Sulfate (pH 8)

-
Data collection

DiffractionMean temperature: 100 K / Serial crystal experiment: N
Diffraction sourceSource: SYNCHROTRON / Site: ALS / Beamline: 8.3.1 / Wavelength: 1 Å
DetectorType: DECTRIS PILATUS 6M / Detector: PIXEL / Date: Mar 27, 2022
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 1 Å / Relative weight: 1
ReflectionResolution: 1.18→40.64 Å / Num. obs: 71372 / % possible obs: 99 % / Redundancy: 4.1 % / Biso Wilson estimate: 15.01 Å2 / CC1/2: 0.999 / Rmerge(I) obs: 0.08 / Rrim(I) all: 0.091 / Net I/σ(I): 15
Reflection shellResolution: 1.18→1.21 Å / Num. unique obs: 6011 / CC1/2: 0.991

-
Processing

Software
NameVersionClassification
PHENIX1.19.2_4158refinement
xia2data reduction
Aimlessdata scaling
PHASERphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT / Starting model: 4.0E+49 / Resolution: 1.18→40.64 Å / SU ML: 0.1122 / Cross valid method: FREE R-VALUE / σ(F): 1.34 / Phase error: 24.8918
Stereochemistry target values: GeoStd + Monomer Library + CDL v1.2
RfactorNum. reflection% reflection
Rfree0.1932 1994 2.79 %
Rwork0.1815 69378 -
obs0.1818 71372 91.33 %
Solvent computationShrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å / Solvent model: FLAT BULK SOLVENT MODEL
Displacement parametersBiso mean: 23.84 Å2
Refinement stepCycle: LAST / Resolution: 1.18→40.64 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms2049 0 65 219 2333
Refine LS restraints
Refine-IDTypeDev idealNumber
X-RAY DIFFRACTIONf_bond_d0.00822187
X-RAY DIFFRACTIONf_angle_d1.08682971
X-RAY DIFFRACTIONf_chiral_restr0.0935301
X-RAY DIFFRACTIONf_plane_restr0.0085386
X-RAY DIFFRACTIONf_dihedral_angle_d17.8851291
LS refinement shell
Resolution (Å)Rfactor RfreeNum. reflection RfreeRfactor RworkNum. reflection RworkRefine-ID% reflection obs (%)
1.18-1.210.29550.34132146X-RAY DIFFRACTION39.65
1.21-1.240.29931120.2783550X-RAY DIFFRACTION66.04
1.24-1.270.28841260.27084369X-RAY DIFFRACTION80.51
1.27-1.320.25721370.25615125X-RAY DIFFRACTION95.07
1.32-1.360.25641610.25475376X-RAY DIFFRACTION99.96
1.36-1.420.2931520.23895397X-RAY DIFFRACTION99.91
1.42-1.480.23171550.22935374X-RAY DIFFRACTION99.87
1.48-1.560.21471560.21845419X-RAY DIFFRACTION99.93
1.56-1.660.21151600.2095397X-RAY DIFFRACTION99.84
1.66-1.790.19091560.20135433X-RAY DIFFRACTION99.8
1.79-1.970.21321580.18395397X-RAY DIFFRACTION99.57
1.97-2.250.19451530.17835412X-RAY DIFFRACTION99.39
2.25-2.830.17961540.17475454X-RAY DIFFRACTION99.5
2.83-40.640.16251590.14845529X-RAY DIFFRACTION98.99
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)
18.89324075484-1.641869840081.344317673253.680667895622.504149419447.0828479497-0.06522324302780.19488100572-0.200753915213-0.367016525833-0.0764573766528-0.6327945282790.1151478574270.3023010848050.1443006381790.1381962893210.002995021739070.07835832851290.1974858440790.02623933534910.23073656486229.9526434116-4.4937785374414.5394694695
24.045741536331.03396328481-2.495132777652.57634922928-1.225046891593.70296792078-0.127871160851-0.362917356743-0.04434167575010.1948949930470.111944781571-0.1879982825940.06977633320170.1828978171690.02901465757490.1691473756950.044064132431-0.03518288439320.215343684278-0.01190043614750.10668134721218.086898305-3.7315458575528.8941635957
32.03848520417-1.27827066068-0.268394912542.58012204712-0.5777365631213.27039316690.108243932862-0.1151956011510.0983163579595-0.2127861182810.05289976720780.176627970567-0.427658525416-0.103753403921-0.1962664912020.174908374652-0.0599501589966-0.05575037478080.127509000063-0.01217896642760.1165659234175.718627450613.2628256889714.0659462823
41.67311473894-1.15801656296-0.1259385797814.590452151450.3302866303671.67656674611-0.0187538677964-0.02709900365410.0114910487286-0.1778716719940.03253798194380.207017901967-0.0681134144208-0.015399065602-0.02514778379440.0870150560099-0.0263995434025-0.01844406501120.118844084203-0.001311890807330.07245717365448.48023238709-1.112459545217.0974137982
51.075786120890.7916969048570.3563994196416.006100493131.598021090781.84283950728-0.0227980846441-0.04027316633460.0738663717361-0.1630573373560.04431004808630.0693117214845-0.139079477240.0706605712413-0.01114242727390.1331396672990.00326608655704-0.0007768375019450.135703877065-0.0009640865324490.0768769111399.520767107174.0311079444317.8702387981
64.212255948133.90922181035-5.936924451795.76982484082-4.66094836798.89603661724-0.3384345527530.7045145024-0.14418543876-0.8683920978980.2432484446620.3235886913470.106949743954-0.5203643581070.1096067210520.337040912705-0.0159922502657-0.08753514960290.19017000811-0.01776968734370.1660883114455.30660045029-6.427384684130.227366113837
71.107498356650.0835449644223-0.005813659315581.492503809140.2534253413531.11533888541-0.01445827537180.05422784103260.0123330020211-0.2191334997760.01902365848780.131056696057-0.0495050803048-0.0554378666237-0.01994918279760.1254929197750.0123706648787-0.01988479695020.09586821361270.01221276430890.06422219832147.93701743401-1.6585187009415.5602633349
85.985092005790.682830355718-2.473492071162.93521394124-1.754108391683.79738317857-0.1060260211270.44649104043-0.102114075673-0.5693931852050.0946546208765-0.2217101401890.01749891338280.3500657639350.007546873957850.316423445499-0.0309662788160.03611343733760.227411350271-0.0362829045010.094030103890916.4601675354-10.92011282370.863228314901
93.22952703222-0.477557714173-0.4998600307642.642337611191.159807565453.58799228621-0.0631419924758-0.365986966526-0.03442700342460.1455539861420.192887096367-0.0665753681958-0.02992647223650.214007599356-0.1472899375010.1129603603330.0115583200128-0.00600869889910.0830759362490.04230205005740.065527737043615.6699394869-6.4819760900823.900844934
Refinement TLS group

Refine-ID: X-RAY DIFFRACTION / Auth asym-ID: A / Label asym-ID: A

IDRefine TLS-IDSelection detailsAuth seq-IDLabel seq-ID
11chain 'A' and (resid 4 through 19 )4 - 191 - 16
22chain 'A' and (resid 20 through 39 )20 - 3917 - 36
33chain 'A' and (resid 40 through 70 )40 - 7037 - 67
44chain 'A' and (resid 71 through 115 )71 - 11568 - 112
55chain 'A' and (resid 116 through 154 )116 - 154113 - 150
66chain 'A' and (resid 155 through 167 )155 - 167151 - 163
77chain 'A' and (resid 168 through 219 )168 - 219164 - 215
88chain 'A' and (resid 220 through 238 )220 - 238216 - 234
99chain 'A' and (resid 239 through 261 )239 - 261235 - 257

+
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