[English] 日本語
Yorodumi
- PDB-4pyx: Crystal structure of human carbonic anhydrase isozyme II with inh... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 4pyx
TitleCrystal structure of human carbonic anhydrase isozyme II with inhibitor
ComponentsCarbonic anhydrase 2
KeywordsLYASE/LYASE INHIBITOR / drug design / carbonic anhydrase / benzenesulfonamide / metal-binding / 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 / 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
Chem-V90 / Carbonic anhydrase 2
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / molecular replacement / Resolution: 1.8 Å
AuthorsSmirnov, A. / Manakova, E. / Grazulis, S.
CitationJournal: J.Med.Chem. / Year: 2014
Title: Discovery and characterization of novel selective inhibitors of carbonic anhydrase IX.
Authors: Dudutiene, V. / Matuliene, J. / Smirnov, A. / Timm, D.D. / Zubriene, A. / Baranauskiene, L. / Morkunaite, V. / Smirnoviene, J. / Michailoviene, V. / Juozapaitiene, V. / Mickeviciute, A. / ...Authors: Dudutiene, V. / Matuliene, J. / Smirnov, A. / Timm, D.D. / Zubriene, A. / Baranauskiene, L. / Morkunaite, V. / Smirnoviene, J. / Michailoviene, V. / Juozapaitiene, V. / Mickeviciute, A. / Kazokaite, J. / Baksyte, S. / Kasiliauskaite, A. / Jachno, J. / Revuckiene, J. / Kisonaite, M. / Pilipuityte, V. / Ivanauskaite, E. / Milinaviciute, G. / Smirnovas, V. / Petrikaite, V. / Kairys, V. / Petrauskas, V. / Norvaisas, P. / Linge, D. / Gibieza, P. / Capkauskaite, E. / Zaksauskas, A. / Kazlauskas, E. / Manakova, E. / Grazulis, S. / Ladbury, J.E. / Matulis, D.
History
DepositionMar 28, 2014Deposition site: RCSB / Processing site: RCSB
Revision 1.0Jan 28, 2015Provider: repository / Type: Initial release
Revision 1.1Sep 20, 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 / pdbx_struct_conn_angle / struct_conn / struct_site
Item: _database_2.pdbx_DOI / _database_2.pdbx_database_accession ..._database_2.pdbx_DOI / _database_2.pdbx_database_accession / _pdbx_struct_conn_angle.ptnr1_auth_comp_id / _pdbx_struct_conn_angle.ptnr1_auth_seq_id / _pdbx_struct_conn_angle.ptnr1_label_asym_id / _pdbx_struct_conn_angle.ptnr1_label_atom_id / _pdbx_struct_conn_angle.ptnr1_label_comp_id / _pdbx_struct_conn_angle.ptnr1_label_seq_id / _pdbx_struct_conn_angle.ptnr3_auth_comp_id / _pdbx_struct_conn_angle.ptnr3_auth_seq_id / _pdbx_struct_conn_angle.ptnr3_label_asym_id / _pdbx_struct_conn_angle.ptnr3_label_atom_id / _pdbx_struct_conn_angle.ptnr3_label_comp_id / _pdbx_struct_conn_angle.ptnr3_label_seq_id / _pdbx_struct_conn_angle.value / _struct_conn.pdbx_dist_value / _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_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 / _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: Carbonic anhydrase 2
hetero molecules


Theoretical massNumber of molelcules
Total (without water)30,0405
Polymers29,2891
Non-polymers7514
Water3,027168
1


  • Idetical with deposited unit
  • defined by author&software
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
MethodPISA
Unit cell
Length a, b, c (Å)42.022, 41.143, 71.519
Angle α, β, γ (deg.)90.000, 104.070, 90.000
Int Tables number4
Space group name H-MP1211

-
Components

-
Protein , 1 types, 1 molecules A

#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 / Plasmid: pET15b / Production host: Escherichia coli (E. coli) / Strain (production host): BL21(DE3) / References: UniProt: P00918, carbonic anhydrase

-
Non-polymers , 5 types, 172 molecules

#2: Chemical ChemComp-ZN / ZINC ION


Mass: 65.409 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: Zn
#3: Chemical ChemComp-DMS / DIMETHYL SULFOXIDE


Mass: 78.133 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C2H6OS / Comment: DMSO, precipitant*YM
#4: Chemical ChemComp-MES / 2-(N-MORPHOLINO)-ETHANESULFONIC ACID


Mass: 195.237 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C6H13NO4S / Comment: pH buffer*YM
#5: Chemical ChemComp-V90 / 2-(cyclooctylamino)-3,5,6-trifluoro-4-[(2-hydroxyethyl)sulfanyl]benzenesulfonamide


Mass: 412.491 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C16H23F3N2O3S2
#6: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 168 / Source method: isolated from a natural source / Formula: H2O

-
Experimental details

-
Experiment

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

-
Sample preparation

CrystalDensity Matthews: 2 Å3/Da / Density % sol: 38 %
Crystal growTemperature: 291 K / Method: vapor diffusion, sitting drop / pH: 7
Details: Crystallization buffer was 0.1M sodium BICINE, pH 9, 0.2 M ammonium sulfate and 2M sodium malonate pH 7 made from 1M sodium BICINE and 3.4M sodium malonate, VAPOR DIFFUSION, SITTING DROP, temperature 291K

-
Data collection

DiffractionMean temperature: 100 K
Diffraction sourceSource: ROTATING ANODE / Type: RIGAKU MICROMAX-007 HF / Wavelength: 1.5418 Å
DetectorType: RIGAKU RAXIS IV++ / Detector: IMAGE PLATE / Date: Oct 30, 2012
RadiationMonochromator: VARIMAX-HF MIRROR / Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 1.5418 Å / Relative weight: 1
ReflectionResolution: 1.8→25.222 Å / Num. obs: 21036 / % possible obs: 95.1 % / Observed criterion σ(F): 0 / Observed criterion σ(I): 0 / Redundancy: 3.7 % / Biso Wilson estimate: 18.529 Å2 / Rmerge(I) obs: 0.127 / Rsym value: 0.127 / Net I/σ(I): 9.9
Reflection shell

Diffraction-ID: 1

Resolution (Å)Redundancy (%)Rmerge(I) obsMean I/σ(I) obsNum. measured allNum. unique allRsym value% possible all
1.8-1.93.70.4221.31078329430.42292
1.9-2.013.70.3331.61045828320.33393.1
2.01-2.153.70.2692981626630.26994.3
2.15-2.323.70.2152.6935825280.21594.6
2.32-2.553.70.1733.2874323670.17396.3
2.55-2.853.70.134.4789921280.1396
2.85-3.293.70.1025.4703419070.10297.3
3.29-4.033.70.0826.7605616560.08298.1
4.03-5.693.60.0756.9463312820.07598.4
5.69-25.223.40.0845.624887300.08497.4

-
Phasing

PhasingMethod: molecular replacement

-
Processing

Software
NameVersionClassificationNB
REFMACrefinement
MOSFLMdata reduction
SCALA3.2.19data scaling
PDB_EXTRACT3.006data extraction
HKL-3000data collection
MOLREPphasing
RefinementMethod to determine structure: molecular replacement
Starting model: PDB ENTRY 3HLJ

3hlj


Resolution: 1.8→25.22 Å / Cor.coef. Fo:Fc: 0.959 / Cor.coef. Fo:Fc free: 0.923 / WRfactor Rfree: 0.227 / WRfactor Rwork: 0.175 / Occupancy max: 1 / Occupancy min: 0.01 / FOM work R set: 0.851 / SU R Cruickshank DPI: 0.163 / SU Rfree: 0.152 / Cross valid method: THROUGHOUT / σ(F): 0 / ESU R: 0.163 / ESU R Free: 0.152 / Stereochemistry target values: MAXIMUM LIKELIHOOD
Details: HYDROGENS HAVE BEEN USED IF PRESENT IN THE INPUT U VALUES : REFINED INDIVIDUALLY
RfactorNum. reflection% reflectionSelection details
Rfree0.23 2095 10 %RANDOM
Rwork0.178 ---
all0.183 21026 --
obs0.183 21026 94.57 %-
Solvent computationIon probe radii: 0.8 Å / Shrinkage radii: 0.8 Å / VDW probe radii: 1.4 Å / Solvent model: MASK
Displacement parametersBiso max: 71.52 Å2 / Biso mean: 18.991 Å2 / Biso min: 7.02 Å2
Baniso -1Baniso -2Baniso -3
1-0.3 Å20 Å2-0.16 Å2
2---1.2 Å20 Å2
3---0.81 Å2
Refinement stepCycle: LAST / Resolution: 1.8→25.22 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms2049 0 38 168 2255
Refine LS restraints
Refine-IDTypeDev idealDev ideal targetNumber
X-RAY DIFFRACTIONr_bond_refined_d0.020.022178
X-RAY DIFFRACTIONr_angle_refined_deg2.1371.9672957
X-RAY DIFFRACTIONr_dihedral_angle_1_deg7.2955262
X-RAY DIFFRACTIONr_dihedral_angle_2_deg37.59824.74799
X-RAY DIFFRACTIONr_dihedral_angle_3_deg15.70115359
X-RAY DIFFRACTIONr_dihedral_angle_4_deg14.848157
X-RAY DIFFRACTIONr_chiral_restr0.1450.2307
X-RAY DIFFRACTIONr_gen_planes_refined0.0130.0211667
LS refinement shellResolution: 1.8→1.847 Å / Total num. of bins used: 20
RfactorNum. reflection% reflection
Rfree0.344 149 -
Rwork0.334 1303 -
all-1452 -
obs--90.81 %

+
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