[English] 日本語
Yorodumi
- PDB-6zja: Helicobacter pylori urease with inhibitor bound in the active site -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 6zja
TitleHelicobacter pylori urease with inhibitor bound in the active site
Components
  • Urease subunit alpha
  • Urease subunit beta
KeywordsHYDROLASE / dodecamer / bi nickel center / enzyme / cytoplasm
Function / homology
Function and homology information


urease complex / urease / urease activity / urea catabolic process / nickel cation binding / cytoplasm
Similarity search - Function
Urease, gamma-beta subunit / : / Urease active site / Urease active site. / Urease nickel binding site / Urease nickel ligands signature. / Urease, beta subunit / Urease, alpha subunit / Urease alpha subunit, C-terminal / Urease, beta subunit superfamily ...Urease, gamma-beta subunit / : / Urease active site / Urease active site. / Urease nickel binding site / Urease nickel ligands signature. / Urease, beta subunit / Urease, alpha subunit / Urease alpha subunit, C-terminal / Urease, beta subunit superfamily / Urease beta subunit / Urease domain profile. / Urease alpha-subunit, N-terminal domain / Urease alpha-subunit, N-terminal domain / Urease, gamma/gamma-beta subunit / Urease, gamma subunit superfamily / : / Urease, gamma subunit / Amidohydrolase family / Metal-dependent hydrolase, composite domain superfamily / Amidohydrolase-related / Metal-dependent hydrolase
Similarity search - Domain/homology
Chem-DJM / NICKEL (II) ION / Urease subunit beta / Urease subunit alpha / Urease subunit alpha / Urease subunit beta
Similarity search - Component
Biological speciesHelicobacter pylori (bacteria)
MethodELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 2 Å
AuthorsLuecke, H. / Cunha, E.
Funding support Norway, United States, 2items
OrganizationGrant numberCountry
Research Council of Norway275207 Norway
National Institutes of Health/National Institute Of Allergy and Infectious Diseases (NIH/NIAID)R01AI78000 United States
CitationJournal: Nat Commun / Year: 2021
Title: Cryo-EM structure of Helicobacter pylori urease with an inhibitor in the active site at 2.0 Å resolution.
Authors: Eva S Cunha / Xiaorui Chen / Marta Sanz-Gaitero / Deryck J Mills / Hartmut Luecke /
Abstract: Infection of the human stomach by Helicobacter pylori remains a worldwide problem and greatly contributes to peptic ulcer disease and gastric cancer. Without active intervention approximately 50% of ...Infection of the human stomach by Helicobacter pylori remains a worldwide problem and greatly contributes to peptic ulcer disease and gastric cancer. Without active intervention approximately 50% of the world population will continue to be infected with this gastric pathogen. Current eradication, called triple therapy, entails a proton-pump inhibitor and two broadband antibiotics, however resistance to either clarithromycin or metronidazole is greater than 25% and rising. Therefore, there is an urgent need for a targeted, high-specificity eradication drug. Gastric infection by H. pylori depends on the expression of a nickel-dependent urease in the cytoplasm of the bacteria. Here, we report the 2.0 Å resolution structure of the 1.1 MDa urease in complex with an inhibitor by cryo-electron microscopy and compare it to a β-mercaptoethanol-inhibited structure at 2.5 Å resolution. The structural information is of sufficient detail to aid in the development of inhibitors with high specificity and affinity.
History
DepositionJun 28, 2020Deposition site: PDBE / Processing site: PDBE
Revision 1.0Dec 23, 2020Provider: repository / Type: Initial release
Revision 1.1Feb 3, 2021Group: Database references / Category: citation / citation_author
Item: _citation.country / _citation.journal_abbrev ..._citation.country / _citation.journal_abbrev / _citation.journal_id_CSD / _citation.journal_id_ISSN / _citation.journal_volume / _citation.page_first / _citation.page_last / _citation.pdbx_database_id_DOI / _citation.pdbx_database_id_PubMed / _citation.title / _citation.year

-
Structure visualization

Movie
  • Deposited structure unit
  • Imaged by Jmol
  • Download
  • Superimposition on EM map
  • EMDB-11233
  • Imaged by UCSF Chimera
  • Download
Movie viewer
Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: Urease subunit alpha
B: Urease subunit beta
C: Urease subunit alpha
E: Urease subunit alpha
G: Urease subunit alpha
I: Urease subunit alpha
K: Urease subunit alpha
M: Urease subunit alpha
O: Urease subunit alpha
Q: Urease subunit alpha
S: Urease subunit alpha
U: Urease subunit alpha
W: Urease subunit alpha
J: Urease subunit beta
D: Urease subunit beta
F: Urease subunit beta
H: Urease subunit beta
L: Urease subunit beta
N: Urease subunit beta
P: Urease subunit beta
R: Urease subunit beta
T: Urease subunit beta
V: Urease subunit beta
X: Urease subunit beta
hetero molecules


Theoretical massNumber of molelcules
Total (without water)1,066,47660
Polymers1,061,73924
Non-polymers4,73736
Water57,4863191
1


  • Idetical with deposited unit
  • defined by author&software
  • Evidence: gel filtration
TypeNameSymmetry operationNumber
identity operation1_5551
Buried area203100 Å2
ΔGint-1004 kcal/mol
Surface area269030 Å2
MethodPISA

-
Components

#1: Protein
Urease subunit alpha / Urea amidohydrolase subunit alpha


Mass: 26645.703 Da / Num. of mol.: 12
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Helicobacter pylori (bacteria) / Gene: ureA, BGL58_00110, D2C78_00705, DD749_00755 / Production host: Escherichia coli (E. coli)
References: UniProt: A0A293SGE9, UniProt: P14916*PLUS, urease
#2: Protein
Urease subunit beta / Urea amidohydrolase subunit beta


Mass: 61832.531 Da / Num. of mol.: 12
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Helicobacter pylori (bacteria)
Gene: ureC, ureB, ACM26_03100, ACM31_01665, AEY53_07315, AEY54_04500, BB390_03210, BB400_00890, BB458_02040, BB472_00115, BB483_06885, BCM300_00080, BGL59_06905, BGL62_00955, BGL74_08355, BGL78_ ...Gene: ureC, ureB, ACM26_03100, ACM31_01665, AEY53_07315, AEY54_04500, BB390_03210, BB400_00890, BB458_02040, BB472_00115, BB483_06885, BCM300_00080, BGL59_06905, BGL62_00955, BGL74_08355, BGL78_03465, BGL80_00980, BZK19_03120, BZK22_02015, BZK28_01040, C2R48_07340, C2R49_05480, C2R51_07515, C2R54_00600, C2R57_07640, C2R76_03750, C2R81_00275, C2R85_01915, C2R92_02560, CV727_07335, CV730_01155, D2C74_07740, D2C77_03985, D2C79_06860, DD741_00890, DD749_00750, DD779_00665, DD783_00075, DDP32_00750, DDP35_00500, EC528_04020, EC532_02160, EC572_01665, EC592_02340, EC594_04345, EC598_01685, ECB88_00905, ECB90_01230, ECC11_01355, ECC14_06065, ECC20_02355, ECC23_04175, ECC26_01225, ECC27_04455, ECC29_00335, ECC38_01340, ECC45_00115, ECE48_05900, EDB75_03310, EPC84_05055, HPY1198_04550, NCTC13207_01207, NCTC13338_01433, NCTC13345_00234
Production host: Escherichia coli (E. coli)
References: UniProt: A0A086RWB6, UniProt: P69996*PLUS, urease
#3: Chemical...
ChemComp-NI / NICKEL (II) ION


Mass: 58.693 Da / Num. of mol.: 24 / Source method: obtained synthetically / Formula: Ni
#4: Chemical
ChemComp-DJM / 2-{[1-(3,5-dimethylphenyl)-1H-imidazol-2-yl]sulfanyl}-N-hydroxyacetamide


Mass: 277.342 Da / Num. of mol.: 12 / Source method: obtained synthetically / Formula: C13H15N3O2S
#5: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 3191 / Source method: isolated from a natural source / Formula: H2O
Has ligand of interestY

-
Experimental details

-
Experiment

ExperimentMethod: ELECTRON MICROSCOPY
EM experimentAggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction

-
Sample preparation

ComponentName: 1.1 MDa Helicobacter pylori Urease / Type: COMPLEX / Entity ID: #1-#2 / Source: RECOMBINANT
Molecular weightValue: 1.1 MDa / Experimental value: NO
Source (natural)Organism: Helicobacter pylori (bacteria) / Strain: UMAB41 / Cellular location: Cytoplasm
Source (recombinant)Organism: Escherichia coli (E. coli) / Plasmid: pHP808, pHP902
Buffer solutionpH: 8
Buffer component
IDConc.NameBuffer-ID
120 mMHepes1
21 mMEDTA1
31 mMBME1
SpecimenConc.: 2 mg/ml / Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES
VitrificationInstrument: FEI VITROBOT MARK IV / Cryogen name: ETHANE / Humidity: 70 % / Chamber temperature: 283 K

-
Electron microscopy imaging

Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company
MicroscopyModel: FEI TITAN KRIOS
Electron gunElectron source: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: FLOOD BEAM
Electron lensMode: BRIGHT FIELD
Image recordingElectron dose: 50 e/Å2 / Film or detector model: GATAN K2 SUMMIT (4k x 4k) / Num. of grids imaged: 1 / Num. of real images: 956 / Details: Used 718 movies

-
Processing

SoftwareName: PHENIX / Version: 1.18.1_3865: / Classification: refinement
EM software
IDNameVersionCategory
4RELION3.0 betaCTF correction
7Coot0.8.9model fitting
9RELION3.0 betainitial Euler assignment
10RELION3.0 betafinal Euler assignment
11RELION3.0 betaclassification
12RELION3.0 beta3D reconstruction
13PHENIX1.18model refinement
CTF correctionDetails: Relion 3.0 beta per image and per particle / Type: NONE
Particle selectionNum. of particles selected: 203000
SymmetryPoint symmetry: T (tetrahedral)
3D reconstructionResolution: 2 Å / Resolution method: FSC 0.5 CUT-OFF / Num. of particles: 187461 / Details: Relion was used for resconstruction / Num. of class averages: 1 / Symmetry type: POINT
Atomic model buildingProtocol: RIGID BODY FIT / Space: REAL
Atomic model building
IDPDB-IDPdb chain-ID 3D fitting-ID
11E9Z

1e9z

A1
21E9Z

1e9z

B1
Refine LS restraints
Refine-IDTypeDev idealNumber
ELECTRON MICROSCOPYf_bond_d0.00576092
ELECTRON MICROSCOPYf_angle_d0.854102648
ELECTRON MICROSCOPYf_dihedral_angle_d18.08928296
ELECTRON MICROSCOPYf_chiral_restr0.05711400
ELECTRON MICROSCOPYf_plane_restr0.00613440

+
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