[English] 日本語
Yorodumi Papers
- Database of articles cited by EMDB/PDB/SASBDB data -

+
Search query

Keywords
Structure methods
Author
Journal
IF

-
Structure paper

TitleHelical ultrastructure of the metalloprotease meprin α in complex with a small molecule inhibitor.
Journal, issue, pagesNat Commun, Vol. 13, Issue 1, Page 6178, Year 2022
Publish dateOct 19, 2022
AuthorsCharles Bayly-Jones / Christopher J Lupton / Claudia Fritz / Hariprasad Venugopal / Daniel Ramsbeck / Michael Wermann / Christian Jäger / Alex de Marco / Stephan Schilling / Dagmar Schlenzig / James C Whisstock /
PubMed AbstractThe zinc-dependent metalloprotease meprin α is predominantly expressed in the brush border membrane of proximal tubules in the kidney and enterocytes in the small intestine and colon. In normal ...The zinc-dependent metalloprotease meprin α is predominantly expressed in the brush border membrane of proximal tubules in the kidney and enterocytes in the small intestine and colon. In normal tissue homeostasis meprin α performs key roles in inflammation, immunity, and extracellular matrix remodelling. Dysregulated meprin α is associated with acute kidney injury, sepsis, urinary tract infection, metastatic colorectal carcinoma, and inflammatory bowel disease. Accordingly, meprin α is the target of drug discovery programs. In contrast to meprin β, meprin α is secreted into the extracellular space, whereupon it oligomerises to form giant assemblies and is the largest extracellular protease identified to date (~6 MDa). Here, using cryo-electron microscopy, we determine the high-resolution structure of the zymogen and mature form of meprin α, as well as the structure of the active form in complex with a prototype small molecule inhibitor and human fetuin-B. Our data reveal that meprin α forms a giant, flexible, left-handed helical assembly of roughly 22 nm in diameter. We find that oligomerisation improves proteolytic and thermal stability but does not impact substrate specificity or enzymatic activity. Furthermore, structural comparison with meprin β reveal unique features of the active site of meprin α, and helical assembly more broadly.
External linksNat Commun / PubMed:36261433 / PubMed Central
MethodsEM (single particle) / EM (subtomogram averaging)
Resolution2.4 - 12.7 Å
Structure data

26419

7uab

EMDB-26419: Human pro-meprin alpha (zymogen state)[subparticle localised reconstruction]
PDB-7uab: Human pro-meprin alpha (zymogen state)
Method: EM (single particle) / Resolution: 3.7 Å

26420

7uac

EMDB-26420: Human pro-meprin alpha (zymogen state)[Focused classification and refinement]
PDB-7uac: Human pro-meprin alpha (zymogen state)
Method: EM (single particle) / Resolution: 2.7 Å

EMDB-26421: Meprin alpha helix (activated) - full C1 consensus reconstruction
Method: EM (single particle) / Resolution: 3.4 Å

26422

7uae

EMDB-26422: Human meprin alpha (active state)[subparticle localised reconstruction]
PDB-7uae: Human meprin alpha (active state)
Method: EM (single particle) / Resolution: 2.6 Å

26423

7uaf

EMDB-26423, PDB-7uaf:
Human meprin alpha inhibitory complex with compound 10d (N~3~,N~3~-bis[(2H-1,3-benzodioxol-5-yl)methyl]-N-hydroxy-beta-alaninamide)
Method: EM (single particle) / Resolution: 2.4 Å

EMDB-26424: Meprin alpha helix in complex with fetuin-B [consensus C1 reconstruction]
Method: EM (single particle) / Resolution: 3.7 Å

26426

7uai

EMDB-26426: Meprin alpha helix in complex with fetuin-B [subparticle localised reconstruction, masked focused refinement]
PDB-7uai: Meprin alpha helix in complex with fetuin-B
Method: EM (single particle) / Resolution: 2.8 Å

EMDB-27689: Sub-tomogram average of pro-meprin alpha supercoiled filament
Method: EM (subtomogram averaging) / Resolution: 12.7 Å

Chemicals

ChemComp-NAG:
2-acetamido-2-deoxy-beta-D-glucopyranose

ChemComp-CA:
Unknown entry

ChemComp-ZN:
Unknown entry

ChemComp-M6X:
N~3~,N~3~-bis[(2H-1,3-benzodioxol-5-yl)methyl]-N-hydroxy-beta-alaninamide

Source
  • homo sapiens (human)
  • Homo sapeins (others)
KeywordsONCOPROTEIN / Metalloprotease / complex / helical / extracellular

+
About Yorodumi Papers

-
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 Papers

Database of articles cited by EMDB/PDB/SASBDB data

  • Database of articles cited by EMDB, PDB, and SASBDB entries
  • Using PubMed data

Related info.:EMDB / PDB / SASBDB / Yorodumi / EMN Papers / Changes in new EM Navigator and Yorodumi

Read more