9UHB

BCCP-CT Conformation of AMPPNP-bound hPCC

9UHB の概要

• エントリーDOI: 10.2210/pdb9uhb/pdb
• EMDBエントリー: 64161
• 分子名称: Propionyl-CoA carboxylase alpha chain, mitochondrial, Propionyl-CoA carboxylase beta chain, mitochondrial, BIOTIN, ... (7 entities in total)
• 機能のキーワード: carboxylase, transferase
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 140063.00

構造登録者

Ni, F.Y.,Yan, H.F.,Wang, Q.H.,Ma, J.P. (登録日: 2025-04-14, 公開日: 2025-11-19, 最終更新日: 2026-01-21)

主引用文献

Yan, H.,Ni, F.,Wang, Q.,Ma, J.
Nanoscale conformational dynamics of human propionyl-CoA carboxylase.
Structure, 34:62-75.e4, 2026

PubMed Abstract: Propionyl-CoA carboxylase (PCC) is a biotin-dependent mitochondrial enzyme responsible for propionyl-CoA catabolism. Deficiencies in human PCC (hPCC) cause propionic acidemia, a severe metabolic disorder driven by toxic metabolite accumulation. Despite its therapeutic relevance, the structural basis of hPCC's catalytic function remains unresolved. Here, we present high-resolution cryo-EM structures of hPCC in four distinct states, unliganded, ADP-, AMPPNP-, and ATP-bound/substrate-bound, capturing the full trajectory of the biotin carboxyl carrier protein (BCCP) domain as it translocates between active sites. Our results reinforce the crucial role of nucleotide-gated B-lid subdomain in synchronizing catalysis through coupling with BCCP movement. Structural and biochemical analysis of 10 disease-associated variants reveals how mutations disrupt key domain interfaces and dynamic motions required for activity. These new insights define the mechanistic principles governing hPCC functions, establish a structural framework for understanding PCC-related disorders, and lay the groundwork for future efforts to engineer functional replacements or modulators for metabolic therapy.

PubMed: 41197621
DOI: 10.1016/j.str.2025.10.009

実験手法

ELECTRON MICROSCOPY (3.16 Å)