9HLD

TRPML1 in complex with compound 13

これはPDB形式変換不可エントリーです。

9HLD の概要

• エントリーDOI: 10.2210/pdb9hld/pdb
• 関連するPDBエントリー: 9HJ6 9HJ8 9HL3 9HL4 9HL6 9HL8 9HLA 9HLB 9HLC
• EMDBエントリー: 52210 52211 52242 52243 52245 52246 52248 52249 52250 52251
• 分子名称: Mucolipin-1, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, N-OCTANE, ... (10 entities in total)
• 機能のキーワード: ion channel, membrane protein
• 由来する生物種: Homo sapiens (human)
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 291366.18

構造登録者

Reeks, J.,Mahajan, P.,Clark, M.,Cowan, S.R.,Di Daniel, E.,Earl, C.P.,Fisher, S.,Holvey, R.S.,Jackson, S.M.,Lloyd-Evans, E.,Morgillo, C.M.,Mortenson, P.N.,O'Reilly, M.,Richardson, C.J.,Schopf, P.,Tams, D.M.,Waller-Evans, H.,Ward, S.E.,Whibley, S.,Williams, P.A.,Johnson, C.N. (登録日: 2024-12-04, 公開日: 2025-06-04, 最終更新日: 2025-12-17)

主引用文献

Reeks, J.,Mahajan, P.,Clark, M.,Cowan, S.R.,Di Daniel, E.,Earl, C.P.,Fisher, S.,Holvey, R.S.,Jackson, S.M.,Lloyd-Evans, E.,Morgillo, C.M.,Mortenson, P.N.,O'Reilly, M.,Richardson, C.J.,Schopf, P.,Tams, D.M.,Waller-Evans, H.,Ward, S.E.,Whibley, S.,Williams, P.A.,Johnson, C.N.
High throughput cryo-EM provides structural understanding for modulators of the lysosomal ion channel TRPML1.
Structure, 33:1374-1385.e7, 2025

PubMed Abstract: Access to high-resolution structural data for protein-ligand complexes is a prerequisite for structure-based medicinal chemistry, where the ability to iterate cycles of design-structure-redesign is highly desirable. For proteins refractory to X-ray crystallography, such as integral membrane proteins, enablement of high throughput structure determination by cryoelectron microscopy (cryo-EM) has the potential to be transformational for structure-based design. We have applied such an approach to the lysosomal ion channel transient receptor potential mucolipin 1 (TRPML1) in complex with ten chemically diverse modulators, both agonists and antagonists. The resulting depth of high-resolution structural data generated provides important insights into protein-ligand structure-function relationships, including mechanistic understanding of ligand-induced channel pore opening and closing. Moreover, the knowledge gained has the potential to support iterative design cycles toward improved modulators of this important biological target.

PubMed: 40532704
DOI: 10.1016/j.str.2025.05.014

実験手法

ELECTRON MICROSCOPY (2.2 Å)