[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

TitleMechanistic insight into allosteric activation of human pyruvate carboxylase by acetyl-CoA.
Journal, issue, pagesMol Cell, Vol. 82, Issue 21, Page 4116-44130.e6, Year 2022
Publish dateNov 3, 2022
AuthorsPeiwei Chai / Pengfei Lan / Shaobai Li / Deqiang Yao / Chenchen Chang / Mi Cao / Yafeng Shen / Shengfang Ge / Jian Wu / Ming Lei / Xianqun Fan /
PubMed AbstractPyruvate carboxylase (PC) catalyzes the two-step carboxylation of pyruvate to produce oxaloacetate, playing a key role in the maintenance of metabolic homeostasis in cells. Given its involvement in ...Pyruvate carboxylase (PC) catalyzes the two-step carboxylation of pyruvate to produce oxaloacetate, playing a key role in the maintenance of metabolic homeostasis in cells. Given its involvement in multiple diseases, PC has been regarded as a potential therapeutic target for obesity, diabetes, and cancer. Albeit acetyl-CoA has been recognized as the allosteric regulator of PC for over 60 years, the underlying mechanism of how acetyl-CoA induces PC activation remains enigmatic. Herein, by using time-resolved cryo-electron microscopy, we have captured the snapshots of PC transitional states during its catalytic cycle. These structures and the biochemical studies reveal that acetyl-CoA stabilizes PC in a catalytically competent conformation, which triggers a cascade of events, including ATP hydrolysis and the long-distance communication between the two reactive centers. These findings provide an integrated picture for PC catalysis and unveil the unique allosteric mechanism of acetyl-CoA in an essential biochemical reaction in all kingdoms of life.
External linksMol Cell / PubMed:36283412
MethodsEM (single particle)
Resolution3.3 - 4.0 Å
Structure data

32773

7wta

EMDB-32773, PDB-7wta:
Cryo-EM structure of human pyruvate carboxylase in apo state
Method: EM (single particle) / Resolution: 3.9 Å

EMDB-32774: PC-(acetyl-CoA) (12.5uM)
Method: EM (single particle) / Resolution: 3.9 Å

32775

7wtb

EMDB-32775, PDB-7wtb:
Cryo-EM structure of human pyruvate carboxylase with acetyl-CoA
Method: EM (single particle) / Resolution: 3.7 Å

EMDB-32776: PC-(acetyl-CoA)(50 uM)
Method: EM (single particle) / Resolution: 3.4 Å

EMDB-32777: PC-(acetyl-CoA)(100 uM)
Method: EM (single particle) / Resolution: 3.6 Å

32778

7wtc

EMDB-32778, PDB-7wtc:
Cryo-EM structure of human pyruvate carboxylase with acetyl-CoA in the ground state
Method: EM (single particle) / Resolution: 4.0 Å

32779

7wtd

EMDB-32779, PDB-7wtd:
Cryo-EM structure of human pyruvate carboxylase with acetyl-CoA in the intermediate state 1
Method: EM (single particle) / Resolution: 3.9 Å

32780

7wte

EMDB-32780, PDB-7wte:
Cryo-EM structure of human pyruvate carboxylase with acetyl-CoA in the intermediate state 2
Method: EM (single particle) / Resolution: 3.3 Å

EMDB-32781: Cryo-EM structure of human pyruvate carboxylase with acetyl-CoA in the intermediate state 3
Method: EM (single particle) / Resolution: 3.9 Å

EMDB-32782: Cryo-EM structure of human pyruvate carboxylase with acetyl-CoA in the intermediate state 4
Method: EM (single particle) / Resolution: 3.9 Å

EMDB-32783: Cryo-EM structure of human pyruvate carboxylase with acetyl-CoA in the intermediate state 5
Method: EM (single particle) / Resolution: 3.8 Å

Chemicals

ChemComp-BTI:
5-(HEXAHYDRO-2-OXO-1H-THIENO[3,4-D]IMIDAZOL-6-YL)PENTANAL

ChemComp-ANP:
PHOSPHOAMINOPHOSPHONIC ACID-ADENYLATE ESTER / AMP-PNP, energy-carrying molecule analogue*YM

ChemComp-ACO:
ACETYL COENZYME *A / Acetyl-CoA

ChemComp-ATP:
ADENOSINE-5'-TRIPHOSPHATE / ATP, energy-carrying molecule*YM / Adenosine triphosphate

ChemComp-COA:
COENZYME A / Coenzyme A

Source
  • homo sapiens (human)
  • human (human)
KeywordsONCOPROTEIN / pyruvate carboxylase

+
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