5YAK

The crystal structure of human IYD Thr239 mutant with ligand 3-Fluorotyrosine (F-Tyr)

5YAK の概要

• エントリーDOI: 10.2210/pdb5yak/pdb
• 分子名称: Iodotyrosine deiodinase 1, FLAVIN MONONUCLEOTIDE, 3-FLUOROTYROSINE, ... (4 entities in total)
• 機能のキーワード: hiyd, fmn, mft, t239a mutant, oxidoreductase
• 由来する生物種: Homo sapiens (Human)
• タンパク質・核酸の鎖数: 6
• 化学式量合計: 187160.84

構造登録者

Hu, J.M.,Rokita, S.E.,Schlessman, J. (登録日: 2017-09-01, 公開日: 2018-08-08, 最終更新日: 2023-11-22)

主引用文献

Hu, J.,Su, Q.,Schlessman, J.L.,Rokita, S.E.
Redox control of iodotyrosine deiodinase
Protein Sci., 28:68-78, 2019

PubMed Abstract: The redox chemistry of flavoproteins is often gated by substrate and iodotyrosine deiodinase (IYD) has the additional ability to switch between reaction modes based on the substrate. Association of fluorotyrosine (F-Tyr), an inert substrate analog, stabilizes single electron transfer reactions of IYD that are not observed in the absence of this ligand. The co-crystal of F-Tyr and a T239A variant of human IYD have now been characterized to provide a structural basis for control of its flavin reactivity. Coordination of F-Tyr in the active site of this IYD closely mimics that of iodotyrosine and only minor perturbations are observed after replacement of an active site Thr with Ala. However, loss of the side chain hydroxyl group removes a key hydrogen bond from flavin and suppresses the formation of its semiquinone intermediate. Even substitution of Thr with Ser decreases the midpoint potential of human IYD between its oxidized and semiquinone forms of flavin by almost 80 mV. This decrease does not adversely affect the kinetics of reductive dehalogenation although an analogous Ala variant exhibits a 6.7-fold decrease in its k /K . Active site ligands lacking the zwitterion of halotyrosine are not able to induce closure of the active site lid that is necessary for promoting single electron transfer and dehalogenation. Under these conditions, a basal two-electron process dominates catalysis as indicated by preferential reduction of nitrophenol rather than deiodination of iodophenol.

PubMed: 30052294
DOI: 10.1002/pro.3479

実験手法

X-RAY DIFFRACTION (2.3 Å)