[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

TitleIntegrative structural and functional analysis of human malic enzyme 3: A potential therapeutic target for pancreatic cancer.
Journal, issue, pagesHeliyon, Vol. 8, Issue 12, Page e12392, Year 2022
Publish dateDec 19, 2022
AuthorsTsehai A J Grell / Mark Mason / Aaron A Thompson / Jose Carlos Gómez-Tamayo / Daniel Riley / Michelle V Wagner / Ruth Steele / Rodrigo F Ortiz-Meoz / Jay Wadia / Paul L Shaffer / Gary Tresadern / Sujata Sharma / Xiaodi Yu /
PubMed AbstractMalic enzymes (ME1, ME2, and ME3) are involved in cellular energy regulation, redox homeostasis, and biosynthetic processes, through the production of pyruvate and reducing agent NAD(P)H. Recent ...Malic enzymes (ME1, ME2, and ME3) are involved in cellular energy regulation, redox homeostasis, and biosynthetic processes, through the production of pyruvate and reducing agent NAD(P)H. Recent studies have implicated the third and least well-characterized isoform, mitochondrial NADP-dependent malic enzyme 3 (ME3), as a therapeutic target for pancreatic cancers. Here, we utilized an integrated structure approach to determine the structures of ME3 in various ligand-binding states at near-atomic resolutions. ME3 is captured in the open form existing as a stable tetramer and its dynamic Domain C is critical for activity. Catalytic assay results reveal that ME3 is a non-allosteric enzyme and does not require modulators for activity while structural analysis suggests that the inner stability of ME3 Domain A relative to ME2 disables allostery in ME3. With structural information available for all three malic enzymes, the foundation has been laid to understand the structural and biochemical differences of these enzymes and could aid in the development of specific malic enzyme small molecule drugs.
External linksHeliyon / PubMed:36590518 / PubMed Central
MethodsEM (single particle) / X-ray diffraction
Resolution1.94 - 2.77 Å
Structure data

27936

8e76

EMDB-27936, PDB-8e76:
Cryo-EM structure of Apo form ME3
Method: EM (single particle) / Resolution: 2.51 Å

27937

8e78

EMDB-27937, PDB-8e78:
Cryo-EM structure of human ME3 in the presence of citrate
Method: EM (single particle) / Resolution: 2.77 Å

27945

8e8o

EMDB-27945, PDB-8e8o:
Cryo-EM structure of human ME3 in the presence of citrate
Method: EM (single particle) / Resolution: 2.77 Å

PDB-8eyn:
Crystal Structure of Human Mitochondrial NADP+ Malic Enzyme 3 in Apo Form
Method: X-RAY DIFFRACTION / Resolution: 1.94 Å

PDB-8eyo:
Crystal Structure of Human Mitochondrial NADP+ Malic Enzyme 3 with NADP bound
Method: X-RAY DIFFRACTION / Resolution: 2.49 Å

Chemicals

ChemComp-NAP:
NADP NICOTINAMIDE-ADENINE-DINUCLEOTIDE PHOSPHATE / Nicotinamide adenine dinucleotide phosphate

ChemComp-CIT:
CITRIC ACID / Citric acid

ChemComp-HOH:
WATER / Water

Source
  • homo sapiens (human)
KeywordsHYDROLASE / ME1 / ME2 / ME3 / NAD(P)-dependent malic enzymes / Integrated structural techniques / crystal structures / cryo-EM structures / drug discovery / allosteric mechanism / OXIDOREDUCTASE / Malic Enzyme / Rossmann fold / NADP(+)-binding

+
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