5EEH

Crystal structure of carminomycin-4-O-methyltransferase DnrK in complex with SAH and 2-chloro-4-nitrophenol

5EEH の概要

• エントリーDOI: 10.2210/pdb5eeh/pdb
• 関連するPDBエントリー: 5EEG
• 分子名称: Carminomycin 4-O-methyltransferase DnrK, S-ADENOSYL-L-HOMOCYSTEINE, 2-chloranyl-4-nitro-phenol, ... (5 entities in total)
• 機能のキーワード: unnatural substrate, structural genomics, psi-biology, protein structure initiative, enzyme discovery for natural product biosynthesis, natpro, transferase
• 由来する生物種: Streptomyces peucetius
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 127622.33

構造登録者

Wang, F.,Singh, S.,Thorson, J.S.,Phillips Jr., G.N.,Enzyme Discovery for Natural Product Biosynthesis (NatPro) (登録日: 2015-10-22, 公開日: 2015-12-16, 最終更新日: 2023-09-27)

主引用文献

Huber, T.D.,Wang, F.,Singh, S.,Johnson, B.R.,Zhang, J.,Sunkara, M.,Van Lanen, S.G.,Morris, A.J.,Phillips, G.N.,Thorson, J.S.
Functional AdoMet Isosteres Resistant to Classical AdoMet Degradation Pathways.
Acs Chem.Biol., 11:2484-2491, 2016

PubMed Abstract: S-adenosyl-l-methionine (AdoMet) is an essential enzyme cosubstrate in fundamental biology with an expanding range of biocatalytic and therapeutic applications. We report the design, synthesis, and evaluation of stable, functional AdoMet isosteres that are resistant to the primary contributors to AdoMet degradation (depurination, intramolecular cyclization, and sulfonium epimerization). Corresponding biochemical and structural studies demonstrate the AdoMet surrogates to serve as competent enzyme cosubstrates and to bind a prototypical class I model methyltransferase (DnrK) in a manner nearly identical to AdoMet. Given this conservation in function and molecular recognition, the isosteres presented are anticipated to serve as useful surrogates in other AdoMet-dependent processes and may also be resistant to, and/or potentially even inhibit, other therapeutically relevant AdoMet-dependent metabolic transformations (such as the validated drug target AdoMet decarboxylase). This work also highlights the ability of the prototypical class I model methyltransferase DnrK to accept non-native surrogate acceptors as an enabling feature of a new high-throughput methyltransferase assay.

PubMed: 27351335
DOI: 10.1021/acschembio.6b00348

実験手法

X-RAY DIFFRACTION (1.82 Å)