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Open data
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Basic information
Entry | Database: EMDB / ID: EMD-4629 | ||||||||||||
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Title | Helicobacter pylori urease with BME bound in the active site | ||||||||||||
![]() | unmasked map | ||||||||||||
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Function / homology | ![]() urease complex / urease / urease activity / urea catabolic process / nickel cation binding / cytoplasm Similarity search - Function | ||||||||||||
Biological species | ![]() ![]() | ||||||||||||
Method | single particle reconstruction / cryo EM / Resolution: 2.4 Å | ||||||||||||
![]() | Luecke H / Cunha E | ||||||||||||
Funding support | ![]() ![]()
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![]() | ![]() 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 |
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Structure visualization
Movie |
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Structure viewer | EM map: ![]() ![]() ![]() |
Supplemental images |
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Downloads & links
-EMDB archive
Map data | ![]() | 13.1 MB | ![]() | |
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Header (meta data) | ![]() ![]() | 23.5 KB 23.5 KB | Display Display | ![]() |
FSC (resolution estimation) | ![]() | 10.6 KB | Display | ![]() |
Images | ![]() | 242.7 KB | ||
Masks | ![]() | 103 MB | ![]() | |
Others | ![]() ![]() ![]() | 13.1 MB 80.6 MB 80.6 MB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 6qsuMC ![]() 6zjaC M: atomic model generated by this map C: citing same article ( |
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Similar structure data |
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Links
EMDB pages | ![]() ![]() |
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Related items in Molecule of the Month |
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Map
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Annotation | unmasked map | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 1.077 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
CCP4 map header:
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-Supplemental data
-Mask #1
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Density Histograms |
-Additional map: density modified map
File | emd_4629_additional_1.map | ||||||||||||
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Annotation | density modified map | ||||||||||||
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Density Histograms |
-Half map: half map
File | emd_4629_half_map_1.map | ||||||||||||
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Annotation | half map | ||||||||||||
Projections & Slices |
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Density Histograms |
-Half map: half map
File | emd_4629_half_map_2.map | ||||||||||||
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Annotation | half map | ||||||||||||
Projections & Slices |
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Density Histograms |
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Sample components
-Entire : 1.1 MDa Helicobacter pylori Urease
Entire | Name: 1.1 MDa Helicobacter pylori Urease |
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Components |
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-Supramolecule #1: 1.1 MDa Helicobacter pylori Urease
Supramolecule | Name: 1.1 MDa Helicobacter pylori Urease / type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1-#2 |
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Source (natural) | Organism: ![]() ![]() |
Recombinant expression | Organism: ![]() ![]() |
Molecular weight | Theoretical: 1.1 MDa |
-Macromolecule #1: Urease subunit alpha
Macromolecule | Name: Urease subunit alpha / type: protein_or_peptide / ID: 1 / Number of copies: 12 / Enantiomer: LEVO / EC number: urease |
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Source (natural) | Organism: ![]() ![]() |
Molecular weight | Theoretical: 26.645703 KDa |
Recombinant expression | Organism: ![]() ![]() |
Sequence | String: MKLTPKELDK LMLHYAGELA RKRKEKGIKL NYVEAVALIS AHIMEEARAG KKTAAELMQE GRTLLKPDDV MDGVASMIHE VGIEAMFPD GTKLVTVHTP IEANGKLVPG ELFLKNEDIT INEGKKAVSV KVKNVGDRPV QIGSHFHFFE VNRCLDFDRE K TFGKRLDI ...String: MKLTPKELDK LMLHYAGELA RKRKEKGIKL NYVEAVALIS AHIMEEARAG KKTAAELMQE GRTLLKPDDV MDGVASMIHE VGIEAMFPD GTKLVTVHTP IEANGKLVPG ELFLKNEDIT INEGKKAVSV KVKNVGDRPV QIGSHFHFFE VNRCLDFDRE K TFGKRLDI ASGTAVRFEP GEEKSVELID IGGNRRIFGF NALVDRQADN ESKKIALHRA KERGFHGTKS DDNYVKTIKE |
-Macromolecule #2: Urease subunit beta
Macromolecule | Name: Urease subunit beta / type: protein_or_peptide / ID: 2 / Number of copies: 12 / Enantiomer: LEVO / EC number: urease |
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Source (natural) | Organism: ![]() ![]() |
Molecular weight | Theoretical: 61.832531 KDa |
Recombinant expression | Organism: ![]() ![]() |
Sequence | String: MKKISRKEYV SMYGPTTGDK VRLGDTDLIA EVEHDYTIYG EELKFGGGKT LREGMSQSNN PSKEELDLII TNALIVDYTG IYKADIGIK DGKIAGIGKG GNKDMQDGVK NNLSVGPATE ALAGEGLIVT AGGIDTHIHF ISPQQIPTAF ASGVTTMIGG G TGPADGTN ...String: MKKISRKEYV SMYGPTTGDK VRLGDTDLIA EVEHDYTIYG EELKFGGGKT LREGMSQSNN PSKEELDLII TNALIVDYTG IYKADIGIK DGKIAGIGKG GNKDMQDGVK NNLSVGPATE ALAGEGLIVT AGGIDTHIHF ISPQQIPTAF ASGVTTMIGG G TGPADGTN ATTITPGRRN LKWMLRAAEE YSMNLGFLAK GNTSNDASLA DQIEAGAIGF (KCX)IHEDWGTTP SAINHALD V ADKYDVQVAI HTDTLNEAGC VEDTMAAIAG RTMHTFHTEG AGGGHAPDII KVAGEHNILP ASTNPTIPFT VNTEAEHMD MLMVCHHLDK SIKEDVQFAD SRIRPQTIAA EDTLHDMGIF SITSSDSQAM GRVGEVITRT WQTADKNKKE FGRLKEEKGD NDNFRIKRY LSKYTINPAI AHGISEYVGS VEVGKVADLV LWSPAFFGVK PNMIIKGGFI ALSQMGDANA SIPTPQPVYY R EMFAHHGK AKYDANITFV SQAAYDKGIK EELGLERQVL PVKNCRNITK KDMQFNDTTA HIEVNPETYH VFVDGKEVTS KP ANKVSLA QLFSIF |
-Macromolecule #3: NICKEL (II) ION
Macromolecule | Name: NICKEL (II) ION / type: ligand / ID: 3 / Number of copies: 24 / Formula: NI |
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Molecular weight | Theoretical: 58.693 Da |
Chemical component information | ![]() ChemComp-NI: |
-Macromolecule #4: BETA-MERCAPTOETHANOL
Macromolecule | Name: BETA-MERCAPTOETHANOL / type: ligand / ID: 4 / Number of copies: 12 / Formula: BME |
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Molecular weight | Theoretical: 78.133 Da |
Chemical component information | ![]() ChemComp-BME: |
-Macromolecule #5: water
Macromolecule | Name: water / type: ligand / ID: 5 / Number of copies: 1178 / Formula: HOH |
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Molecular weight | Theoretical: 18.015 Da |
Chemical component information | ![]() ChemComp-HOH: |
-Experimental details
-Structure determination
Method | cryo EM |
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![]() | single particle reconstruction |
Aggregation state | particle |
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Sample preparation
Concentration | 2 mg/mL | ||||||||
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Buffer | pH: 8 / Component:
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Grid | Model: Quantifoil R2/2 / Material: COPPER / Pretreatment - Type: GLOW DISCHARGE | ||||||||
Vitrification | Cryogen name: ETHANE / Chamber humidity: 70 % / Chamber temperature: 283 K / Instrument: FEI VITROBOT MARK IV |
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Electron microscopy
Microscope | FEI TITAN KRIOS |
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Image recording | #0 - Image recording ID: 1 / #0 - Film or detector model: GATAN K2 SUMMIT (4k x 4k) / #0 - Number grids imaged: 1 / #0 - Number real images: 956 / #0 - Average electron dose: 50.0 e/Å2 / #0 - Details: Used 718 movies / #1 - Image recording ID: 2 / #1 - Film or detector model: GATAN K2 SUMMIT (4k x 4k) / #1 - Average electron dose: 40.0 e/Å2 / #2 - Image recording ID: 3 / #2 - Film or detector model: GATAN K2 SUMMIT (4k x 4k) / #2 - Average electron dose: 40.0 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: ![]() |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD |
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |