9P4D

Crystal Structure of Engineered glutamine binding protein and a Gd-DOTA ligand - Gln bound

これはPDB形式変換不可エントリーです。

9P4D の概要

• エントリーDOI: 10.2210/pdb9p4d/pdb
• 関連するPDBエントリー: 9p4e
• 分子名称: Amino acid ABC transporter substrate-binding protein, GLUTAMINE, ACETATE ION, ... (8 entities in total)
• 機能のキーワード: amino acid abc transporter, substrate binding protein, metal binding protein
• 由来する生物種: Escherichia coli
• タンパク質・核酸の鎖数: 6
• 化学式量合計: 158623.40

構造登録者

Bruchs, A.T.,Wilson, C.A.,Boggs, D.G.,Fatima, S.,Bridwell-Rabb, J.,Olshansky, L. (登録日: 2025-06-16, 公開日: 2026-01-14)

主引用文献

Wilson, C.A.,Bruchs, A.T.,Fatima, S.,Boggs, D.G.,Bridwell-Rabb, J.,Olshansky, L.
Development of a glutamine-responsive MRI contrast agent.
Chem Sci, 2025

PubMed Abstract: Magnetic resonance imaging (MRI) is widely used to visualize disease, and image quality can be improved through use of MRI contrast agents. Currently available agents produce a signal based solely on spatial distribution, but modern metabolic profiling has uncovered a variety of biomarkers for disease. For example, tumors greatly increase their uptake and catabolism of glutamine (Gln), leading to modified local concentration. Our laboratory previously developed a switchable artificial metalloprotein (swArM) platform in which Gln-binding causes a protein conformational change that modifies the physicochemical environment of an installed metallocofactor. Installing MRI-active metallocofactors within swArMs, we present a proof-of-concept approch toward the development of an analyte-responsive MRI contrast agent. To develop these swArMs, we tested several MRI-active metals (Gd, Dy), chelating ligands (DOTA, DTPA, NOTA), and attachment sites, as well as the impacts of peripheral mutations on the Gln-responsive signal. In each case, metal content was analytically defined, and Gln-binding affinity was determined by isothermal titration calorimetry. Circular dichroism was used to verify that our swArMs could still undergo the conformational change. X-ray diffraction structures of the and swArMs further revealed that the metallocofactor is significantly solvent-exposed in both conformations, but exhibits additional interactions with the protein in the state coinciding with the observed increase in relaxivity of ∼60% upon Gln-binding.

PubMed: 41395538
DOI: 10.1039/d5sc05987a

実験手法

X-RAY DIFFRACTION (2.57 Å)