5NOV

Structure of cyclophilin A in complex with hexahydropyrimidine-2-thione

5NOV の概要

• エントリーDOI: 10.2210/pdb5nov/pdb
• 分子名称: Peptidyl-prolyl cis-trans isomerase A, 1,3-diazinane-2-thione (3 entities in total)
• 機能のキーワード: ligand complex, beta barrel, prolyl cis/trans isomerase, cytosolic, isomerase
• 由来する生物種: Homo sapiens (Human)
• 細胞内の位置: Cytoplasm : P62937
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 18152.69

構造登録者

Georgiou, C.,Mcnae, I.W.,Ioannidis, H.,Julien, M.,Walkinshaw, M.D. (登録日: 2017-04-13, 公開日: 2017-07-12, 最終更新日: 2024-01-17)

主引用文献

Georgiou, C.,McNae, I.,Wear, M.,Ioannidis, H.,Michel, J.,Walkinshaw, M.
Pushing the Limits of Detection of Weak Binding Using Fragment-Based Drug Discovery: Identification of New Cyclophilin Binders.
J. Mol. Biol., 429:2556-2570, 2017

PubMed Abstract: Fragment-based drug discovery is an increasingly popular method to identify novel small-molecule drug candidates. One of the limitations of the approach is the difficulty of accurately characterizing weak binding events. This work reports a combination of X-ray diffraction, surface plasmon resonance experiments and molecular dynamics simulations for the characterization of binders to different isoforms of the cyclophilin (Cyp) protein family. Although several Cyp inhibitors have been reported in the literature, it has proven challenging to achieve high binding selectivity for different isoforms of this protein family. The present studies have led to the identification of several structurally novel fragments that bind to diverse Cyp isoforms in distinct pockets with low millimolar dissociation constants. A detailed comparison of the merits and drawbacks of the experimental and computational techniques is presented, and emerging strategies for designing ligands with enhanced isoform specificity are described.

PubMed: 28673552
DOI: 10.1016/j.jmb.2017.06.016

実験手法

X-RAY DIFFRACTION (2 Å)