6YW3

HIF PROLYL HYDROXYLASE 2 (PHD2/ EGLN1) in complex with N-Oxalyl Glycine (NOG), HIF-1ALPHA CODD (556-574) and a RaPID-derived cyclic peptide 3C (14-mer)

6YW3 の概要

• エントリーDOI: 10.2210/pdb6yw3/pdb
• 関連するPDBエントリー: 5L9B 5L9R 5L9V 6YW1 6YW2
• 分子名称: Egl nine homolog 1, PHD2-SPECIFIC RaPID CYCLIC PEPTIDE 3C (14-MER), Hypoxia-inducible factor 1-alpha, ... (8 entities in total)
• 機能のキーワード: oxidoreductase, non-heme dioxygenase, iron, 2-oxoglutarate, hypoxia-inducible factor, hif, hif prolyl hydroxylase domain 2, phd2, egln1, oxygenase, hypoxia, dna-binding, metal-binding, transcription, helix-loop-helix-beta, dsbh, facial triad, cytoplasm, transcription/epigenetic regulation, signaling, development, cell structure, beta-hydroxylation, transcription activator/inhibitor, ubl conjugation, polymorphism, vitamin c, zinc-finger, familial erythrocytosis, breast cancer, transcription complex
• 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: 30482.34

構造登録者

Chowdhury, R.,Schofield, C.J. (登録日: 2020-04-29, 公開日: 2020-12-30, 最終更新日: 2024-01-24)

主引用文献

Chowdhury, R.,Abboud, M.I.,McAllister, T.E.,Banerji, B.,Bhushan, B.,Sorensen, J.L.,Kawamura, A.,Schofield, C.J.
Use of cyclic peptides to induce crystallization: case study with prolyl hydroxylase domain 2.
Sci Rep, 10:21964-21964, 2020

PubMed Abstract: Crystallization is the bottleneck in macromolecular crystallography; even when a protein crystallises, crystal packing often influences ligand-binding and protein-protein interaction interfaces, which are the key points of interest for functional and drug discovery studies. The human hypoxia-inducible factor prolyl hydroxylase 2 (PHD2) readily crystallises as a homotrimer, but with a sterically blocked active site. We explored strategies aimed at altering PHD2 crystal packing by protein modification and molecules that bind at its active site and elsewhere. Following the observation that, despite weak inhibition/binding in solution, succinamic acid derivatives readily enable PHD2 crystallization, we explored methods to induce crystallization without active site binding. Cyclic peptides obtained via mRNA display bind PHD2 tightly away from the active site. They efficiently enable PHD2 crystallization in different forms, both with/without substrates, apparently by promoting oligomerization involving binding to the C-terminal region. Although our work involves a specific case study, together with those of others, the results suggest that mRNA display-derived cyclic peptides may be useful in challenging protein crystallization cases.

PubMed: 33319810
DOI: 10.1038/s41598-020-76307-8

実験手法

X-RAY DIFFRACTION (2.279 Å)