[English] 日本語
Yorodumi- EMDB-22630: Partial open state of Mycobacterium tuberculosis zinc metalloprot... -
+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-22630 | |||||||||
---|---|---|---|---|---|---|---|---|---|---|
Title | Partial open state of Mycobacterium tuberculosis zinc metalloprotease 1 | |||||||||
Map data | ||||||||||
Sample |
| |||||||||
Keywords | Open state / HYDROLASE | |||||||||
Function / homology | Function and homology information Hydrolases; Acting on peptide bonds (peptidases); Metalloendopeptidases / protein processing / metalloendopeptidase activity / metal ion binding / plasma membrane Similarity search - Function | |||||||||
Biological species | Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv) (bacteria) | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 4.6 Å | |||||||||
Authors | Mancl JM / Liang WG | |||||||||
Funding support | United States, 1 items
| |||||||||
Citation | Journal: Structure / Year: 2021 Title: Structural analysis of Mycobacterium tuberculosis M13 metalloprotease Zmp1 open states. Authors: Wenguang G Liang / Jordan M Mancl / Minglei Zhao / Wei-Jen Tang / Abstract: Zinc metalloprotease 1 (Zmp1), a Mycobacterium tuberculosis 75 kDa secreted enzyme, mediates key stages of tuberculosis disease progression. The biological activity of Zmp1 presumably stems from its ...Zinc metalloprotease 1 (Zmp1), a Mycobacterium tuberculosis 75 kDa secreted enzyme, mediates key stages of tuberculosis disease progression. The biological activity of Zmp1 presumably stems from its ability to degrade bacterium- and/or host-derived peptides. The crystal structures of Zmp1 and related M13 metalloproteases, such as neprilysin and endothelin-converting enzyme-1 were determined only in the closed conformation, which cannot capture substrates or release proteolytic products. Thus, the mechanisms of substrate binding and selectivity remain elusive. Here we report two open-state cryo-EM structures of Zmp1, revealed by our SAXS analysis to be the dominant states in solution. Our structural analyses reveal how ligand binding induces a conformational switch in four linker regions to drive the rigid body motion of the D1 and D2 domains, which form the sizable catalytic chamber. Furthermore, they offer insights into the catalytic cycle and mechanism of substrate recognition of M13 metalloproteases for future therapeutic innovations. | |||||||||
History |
|
-Structure visualization
Movie |
Movie viewer |
---|---|
Structure viewer | EM map: SurfViewMolmilJmol/JSmol |
Supplemental images |
-Downloads & links
-EMDB archive
Map data | emd_22630.map.gz | 20.7 MB | EMDB map data format | |
---|---|---|---|---|
Header (meta data) | emd-22630-v30.xml emd-22630.xml | 12 KB 12 KB | Display Display | EMDB header |
Images | emd_22630.png | 67.2 KB | ||
Filedesc metadata | emd-22630.cif.gz | 5.7 KB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-22630 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-22630 | HTTPS FTP |
-Validation report
Summary document | emd_22630_validation.pdf.gz | 494.1 KB | Display | EMDB validaton report |
---|---|---|---|---|
Full document | emd_22630_full_validation.pdf.gz | 493.7 KB | Display | |
Data in XML | emd_22630_validation.xml.gz | 5.9 KB | Display | |
Data in CIF | emd_22630_validation.cif.gz | 6.7 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-22630 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-22630 | HTTPS FTP |
-Related structure data
Related structure data | 7k1vMC 6xlyC C: citing same article (ref.) M: atomic model generated by this map |
---|---|
Similar structure data |
-Links
EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
---|---|
Related items in Molecule of the Month |
-Map
File | Download / File: emd_22630.map.gz / Format: CCP4 / Size: 22.2 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Voxel size | X=Y=Z: 1.063 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Density |
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
CCP4 map header:
|
-Supplemental data
-Sample components
-Entire : Mycobacterium tuberculosis zinc metalloprotease partial open state
Entire | Name: Mycobacterium tuberculosis zinc metalloprotease partial open state |
---|---|
Components |
|
-Supramolecule #1: Mycobacterium tuberculosis zinc metalloprotease partial open state
Supramolecule | Name: Mycobacterium tuberculosis zinc metalloprotease partial open state type: complex / ID: 1 / Parent: 0 / Macromolecule list: all |
---|---|
Source (natural) | Organism: Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv) (bacteria) Strain: ATCC 25618 / H37Rv |
-Macromolecule #1: Zinc metalloprotease
Macromolecule | Name: Zinc metalloprotease / type: protein_or_peptide / ID: 1 / Number of copies: 1 / Enantiomer: LEVO EC number: Hydrolases; Acting on peptide bonds (peptidases); Metalloendopeptidases |
---|---|
Source (natural) | Organism: Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv) (bacteria) |
Molecular weight | Theoretical: 78.019797 KDa |
Recombinant expression | Organism: Escherichia coli BL21(DE3) (bacteria) |
Sequence | String: MRGSHHHHHH GMASMTGGQQ MGRDLYDDDD KDHPFTMTLA IPSGIDLSHI DADARPQDDL FGHVNGRWLA EHEIPADRAT DGAFRSLFD RAETQVRDLI IQASQAGAAV GTDAQRIGDL YASFLDEEAV ERAGVQPLHD ELATIDSAAD ATELAAALGT L QRAGVGGG ...String: MRGSHHHHHH GMASMTGGQQ MGRDLYDDDD KDHPFTMTLA IPSGIDLSHI DADARPQDDL FGHVNGRWLA EHEIPADRAT DGAFRSLFD RAETQVRDLI IQASQAGAAV GTDAQRIGDL YASFLDEEAV ERAGVQPLHD ELATIDSAAD ATELAAALGT L QRAGVGGG IGVYVDTDSK DSTRYLVHFT QSGIGLPDES YYRDEQHAAV LAAYPGHIAR MFGLVYGGES RDHAKTADRI VA LETKLAD AHWDVVKRRD ADLGYNLRTF AQLQTEGAGF DWVSWVTALG SAPDAMTELV VRQPDYLVTF ASLWASVNVE DWK CWARWR LIRARAPWLT RALVAEDFEF YGRTLTGAQQ LRDRWKRGVS LVENLMGDAV GKLYVQRHFP PDAKSRIDTL VDNL QEAYR ISISELDWMT PQTRQRALAK LNKFTAKVGY PIKWRDYSKL AIDRDDLYGN VQRGYAVNHD RELAKLFGPV DRDEW FMTP QTVNAYYNPG MNEIVFPAAI LQPPFFDPQA DEAANYGGIG AVIGHEIGHG FDDQGAKYDG DGNLVDWWTD DDRTEF AAR TKALIEQYHA YTPRDVDHPG PPHVQGAFTI GENIGDLGGL SIALLAYQLS LNGNPAPVID GLTGMQRVFF GWAQIWR TK SRAAEAIRRL AVDPHSPPEF RCNGVVRNVD AFYQAFDVTE DDALFLDPQR RVRIWN UniProtKB: Zinc metalloprotease |
-Experimental details
-Structure determination
Method | cryo EM |
---|---|
Processing | single particle reconstruction |
Aggregation state | particle |
-Sample preparation
Concentration | 0.8 mg/mL |
---|---|
Buffer | pH: 6.8 Details: 20 mM HEPES, pH 6.8, 150 mM NaCl, 0.5 mM BME, 20 mM Trimethylamine N-oxide dihydrate |
Vitrification | Cryogen name: ETHANE / Chamber humidity: 100 % / Chamber temperature: 308 K / Instrument: FEI VITROBOT MARK II |
-Electron microscopy
Microscope | FEI TITAN KRIOS |
---|---|
Image recording | Film or detector model: GATAN K3 (6k x 4k) / Average exposure time: 5.0 sec. / Average electron dose: 60.0 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
Electron optics | C2 aperture diameter: 70.0 µm / Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Cs: 2.7 mm / Nominal defocus max: 2.8000000000000003 µm / Nominal defocus min: 1.4000000000000001 µm |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |