6FCL

Crystal Structure of Human APRT wild type in complex with AMP

6FCL の概要

• エントリーDOI: 10.2210/pdb6fcl/pdb
• 関連するPDBエントリー: 6FCH 6FCI 6FD4 6FD5 6FD6
• 分子名称: Adenine phosphoribosyltransferase, ADENOSINE MONOPHOSPHATE (3 entities in total)
• 機能のキーワード: rossman fold, transferase
• 由来する生物種: Homo sapiens (Human)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 39549.35

構造登録者

Nioche, P.,Huyet, J.,Ozeir, M. (登録日: 2017-12-20, 公開日: 2018-08-15, 最終更新日: 2024-01-17)

主引用文献

Huyet, J.,Ozeir, M.,Burgevin, M.C.,Pinson, B.,Chesney, F.,Remy, J.M.,Siddiqi, A.R.,Lupoli, R.,Pinon, G.,Saint-Marc, C.,Gibert, J.F.,Morales, R.,Ceballos-Picot, I.,Barouki, R.,Daignan-Fornier, B.,Olivier-Bandini, A.,Auge, F.,Nioche, P.
Structural Insights into the Forward and Reverse Enzymatic Reactions in Human Adenine Phosphoribosyltransferase.
Cell Chem Biol, 25:666-676.e4, 2018

PubMed Abstract: Phosphoribosyltransferases catalyze the displacement of a PRPP α-1'-pyrophosphate to a nitrogen-containing nucleobase. How they control the balance of substrates/products binding and activities is poorly understood. Here, we investigated the human adenine phosphoribosyltransferase (hAPRT) that produces AMP in the purine salvage pathway. We show that a single oxygen atom from the Tyr105 side chain is responsible for selecting the active conformation of the 12 amino acid long catalytic loop. Using in vitro, cellular, and in crystallo approaches, we demonstrated that Tyr105 is key for the fine-tuning of the kinetic activity efficiencies of the forward and reverse reactions. Together, our results reveal an evolutionary pressure on the strictly conserved Tyr105 and on the dynamic motion of the flexible loop in phosphoribosyltransferases that is essential for purine biosynthesis in cells. These data also provide the framework for designing novel adenine derivatives that could modulate, through hAPRT, diseases-involved cellular pathways.

PubMed: 29576532
DOI: 10.1016/j.chembiol.2018.02.011

実験手法

X-RAY DIFFRACTION (1.5 Å)